| ID | Type | Description | Link |
|---|---|---|---|
| 1OT2HL156812-01 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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This is a randomized, open label, adaptive platform trial to compare the effectiveness of antithrombotic and additional strategies for prevention of adverse outcomes in COVID-19 positive inpatients
The severe acute respiratory syndrome coronavirus 2, which causes the highly contagious coronavirus disease 2019 (COVID-19), has resulted in a global pandemic.
The clinical spectrum of COVID-19 infection is broad, encompassing asymptomatic infection, mild upper respiratory tract illness, and severe viral pneumonia with respiratory failure and death. The risk of thrombotic complications is increased, even as compared to other viral respiratory illnesses, such as influenza. A pro-inflammatory cytokine response as well as induction of procoagulant factors associated with COVID-19 has been proposed to contribute to thrombosis as well as plaque rupture through local inflammation. Patients with COVID-19 are at increased risk for arterial and vein thromboembolism, with high rates observed despite thromboprophylaxis. Autopsy reports have noted micro and macro vascular thrombosis across multiple organ beds consistent with an early hypercoagulable state.
Notably, in COVID-19, data in the U.K. and U.S. document that infection and outcomes of infection are worse in African and Hispanic descent persons than in other groups. The reasons for this are uncertain.
Viral Infection and Thrombosis A large body of literature links inflammation and coagulation; altered hemostasis is a known complication of respiratory viral infections. Procoagulant markers are severely elevated in viral infections. Specifically, proinflammatory cytokines in viral infections upregulate expression of tissue factor, markers of thrombin generation, platelet activation, and down-regulate natural anticoagulant proteins C and S.
Studies have demonstrated significant risk of deep venous thrombosis (DVT), pulmonary embolism (PE), and myocardial infarction (MI) associated with viral respiratory infections. In a series of patients with fatal influenza H1N1, 75% had pulmonary thrombi on autopsy (a rate considerably higher than reported on autopsy studies among the general intensive care unit population). Incidence ratio for acute myocardial infarction in the context of Influenza A is over 10. Severe acute respiratory syndrome coronavirus-1 (SARS CoV-1) and influenza have been associated with disseminated intravascular coagulation (DIC), endothelial damage, DVT, PE, and large artery ischemic stroke. Patients with Influenza H1N1 and acute respiratory distress syndrome (ARDS) had a 23.3-fold higher risk for pulmonary embolism, and a 17.9-fold increased risk for deep vein thrombosis. Compared to those treated with systemic anticoagulation, those without treatment were 33 times more likely to suffer a VTE.
Thrombosis, both microvascular and macrovascular, is a prominent feature in multiple organs at autopsy in fatal cases of COVID-19. Thrombosis may thus contribute to respiratory failure, renal failure, and hepatic injury in COVID-19. The number of megakaryocytes in tissues is higher than in other forms of ARDS, and thrombi are platelet-rich based on specific staining. Thrombotic stroke has been reported in young COVID-19 patients with no cardiovascular risk factors. Both arterial and venous thrombotic events have been seen in increasing numbers of hospitalized patients infected with COVID-19. The incidence of thrombosis has ranged from 10 to 30% in hospitalized patients; however, this varies by type of thrombosis captured (arterial or vein) and severity of illness (ICU level care, requiring mechanical ventilation, etc.).
Additional treatment strategies Data from the multiplatform randomized controlled trial (mpRCT) demonstrated that (1) therapeutic dose anticoagulation with heparin was not beneficial in improving clinical outcomes compared to standard of care prophylactic dose heparin in severely ill (ICU level of care) patients, and (2) therapeutic dose anticoagulation with heparin was beneficial in improving organ support free days compared to standard of care prophylactic dose heparin in moderately ill (hospitalized and not requiring organ support) patients. However, there remains significant residual risk for adverse clinical outcomes and excess mortality for severely ill as well as moderately ill patients.
Antithrombotic regimens that are shown to be efficacious will be combined in clinical practice with other agents to treat COVID-19 hospitalized patients. This adaptive platform trial will test other promising agents when added to proven therapies, such as heparin. The rationale and risks for each agent will be included in the arm-specific appendix. Two specific agents to be added as arms, effective October 2021, include the P-selectin inhibitor, Crizanlizumab as well as SGLT2 inhibitors. P-selectin may play a proximal role in the inflammatory and thrombotic cascade in patients with COVID-19 and P-selectin inhibition may be a effective in preventing downstream sequelae. In addition, SGLT-2 inhibitors have been shown to decrease capillary leak and may promote vascular integrity in COVID-19.
This platform trial will have multiple arms, which may be dropped or added as the platform trial progresses. Sample size will be flexible: the trial will be stopped for efficacy or futility based on pre-determined statistical thresholds as defined in the arm-specific appendices. Each arm will have an adaptive component for determinations of futility or success.
Randomization assignments are at the participant level, stratified by enrolling site and by ICU level of care vs non-ICU level of care and/or other arm-specific criteria.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Therapeutic Dose Anticoagulation | Other | increased dose of heparin above standard of care. 1.0 - This arm was stopped in severe patients in December 2020 and results are published in PMID: 34351722 (NEJM, August, 2021) (see reference section for citation). This arm was stopped for moderate patients in January 2021. |
|
| Prophylactic Dose Anticoagulation | Other | Heparin standard of care 1.0 - this arm was stopped for all patients in January, 2021 and results are published in PMID: 34351721 (NEJM, August, 2021) (see reference section for citation) |
|
| Therapeutic Dose Anticoagulation + P2Y12 inhibitor | Other | increased dose of heparin above standard of care with an added P2Y12 inhibitor This Arm enrolled moderate illness patients only. Enrollment of moderate illness patients in the trial was ended per DSMB on June 19, 2021 and results are published in PMID: PMID: 35040887 (JAMA, January, 2022) (see reference section for citation) |
|
| Prophylactic Dose Anticoagulation + P2Y12 inhibitor | Other | Heparin standard of care with an added P2Y12 inhibitor This Arm enrolled severe illness patients only. Enrollment of severe illness patients in the trial was ended per DSMB in June 2022. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| theraputic heparin | Drug | increased dose of heparin above standard of care. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 21 Day Organ Support (Respiratory or Vasopressor) Free Days | which is defined as the number of days that a patient is alive and free of organ support through the first 21 days after trial entry. Organ Support is defined as receipt of non-invasive mechanical ventilation, high flow nasal canula oxygen, mechanical ventilation, or vasopressor therapy, with death at any time during the index hospitalization assigned -1 days. This outcome variable was designed to exceed day 21 on the IQR. It goes above 21 days because it include baseline day 0 in their design. | 21 days from study enrollment |
| Measure | Description | Time Frame |
|---|---|---|
| Death Within 28 Days | 28 days from enrollment | |
| Acute Kidney Injury | Acute Kidney Injury Acute kidney injury after enrollment is defined by KDIGO criteria for Acute Kidney Injury in the setting of not meeting these criteria upon enrollment: Modified Stages: ∙ Stage 2: Serum Cr 2.0-2.9 times baseline ∙ Stage 3: Serum Cr ≥ 3.0 times baseline, OR Increase in serum creatinine to ≥ 4.0mg/dl, OR Initiation of renal replacement therapy |
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Inclusion Criteria:
Exclusion Criteria:
Inclusion Criteria for Arm E
Inclusion criteria contained in the master protocol in addition to the following:
Moderate illness severity - defined as non-ICU level of care at the time of randomization (not receiving high flow nasal oxygen (HFNO), non-invasive ventilation (NIV), invasive ventilation (IV), vasopressors or inotropes, or extracorporeal membrane oxygenation (ECMO) OR Severe illness severity - defined as ICU level of care at the time of randomization (receiving HFNO, NIV, IV, vasopressors or inotropes, or ECMO)
For moderate illness severity, participants are required to meet one or more of the following risk criteria:
Age ≥ 65 years or
≥2 of the following -
Exclusion Criteria for Arm E
Inclusion Criteria for Arm F
Inclusion criteria contained in the master protocol in addition to the following:
Moderate illness severity - defined as non-ICU level of care at the time of randomization (not receiving high flow nasal oxygen (HFNO), non-invasive ventilation (NIV), invasive ventilation (IV), vasopressors or inotropes, or extracorporeal membrane oxygenation (ECMO)) OR Severe illness severity - defined as ICU level of care at the time of randomization (receiving HFNO, NIV, IV, vasopressors or inotropes, or ECMO)
For moderate illness severity, participants are required to meet one or more of the following risk criteria:
Age ≥ 65 years or
≥2 of the following-
Exclusion Criteria for Arm F
In addition to the exclusion criteria noted in the master protocol, arm-specific exclusion criteria are as follows:
Known hypersensitivity to any SGLT2 inhibitors
Type 1 diabetes
History of diabetic ketoacidosis
eGFR <20 and/or requirement for renal replacement therapy
Open label treatment with any SGLT2 inhibitor
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| Name | Affiliation | Role |
|---|---|---|
| Judith Hochman, MD | NYU Langone Health | Study Chair |
| Scott Solomon, MD | Brigham and Women's Hospital | Principal Investigator |
| Mikhail Kosiborod, MD | Saint Lukes | Principal Investigator |
| Jeffrey Berger, MD | NYU Langone Health | Principal Investigator |
| MATTHEW D NEAL, MD | University of Pittsburgh | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama | Birmingham | Alabama | 35233 | United States | ||
| University of Arizona |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32311448 | Background | Bikdeli B, Madhavan MV, Jimenez D, Chuich T, Dreyfus I, Driggin E, Nigoghossian C, Ageno W, Madjid M, Guo Y, Tang LV, Hu Y, Giri J, Cushman M, Quere I, Dimakakos EP, Gibson CM, Lippi G, Favaloro EJ, Fareed J, Caprini JA, Tafur AJ, Burton JR, Francese DP, Wang EY, Falanga A, McLintock C, Hunt BJ, Spyropoulos AC, Barnes GD, Eikelboom JW, Weinberg I, Schulman S, Carrier M, Piazza G, Beckman JA, Steg PG, Stone GW, Rosenkranz S, Goldhaber SZ, Parikh SA, Monreal M, Krumholz HM, Konstantinides SV, Weitz JI, Lip GYH; Global COVID-19 Thrombosis Collaborative Group, Endorsed by the ISTH, NATF, ESVM, and the IUA, Supported by the ESC Working Group on Pulmonary Circulation and Right Ventricular Function. COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-Up: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020 Jun 16;75(23):2950-2973. doi: 10.1016/j.jacc.2020.04.031. Epub 2020 Apr 17. | |
| 32291094 |
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Data will be shared as per NIH guidelines.
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| ID | Title | Description |
|---|---|---|
| FG000 | Therapeutic Dose Anticoagulation | increased dose of heparin above standard of care. 1.0 - This arm was stopped in severe patients in December 2020 and results are published in PMID: 34351722 (NEJM, August, 2021) (see reference section for citation). This arm was stopped for moderate patients in January 2021. theraputic heparin: increased dose of heparin above standard of care. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 19, 2021 | May 28, 2024 |
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This is an adaptive design
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There will be independent masked adjudicators.
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| Standard of Care + Crizanlizumab | Other | Standard of care plus crizanlizumab infusion This arm will enroll moderate and severe illness patients This arm was ended for all patients per the DSMB in September 2022. |
|
| Standard of Care + SGLT2 inhibitor | Other | Standard of care plus SGLT2 inhibitor This arm will enroll moderate and severe illness patients This arm was ended in March 2023 |
|
| Standard of Care (SGLT2 arm) | Other | Standard of care only This arm will enroll moderate and severe illness patients This arm was ended in March 2023 |
|
| Standard of Care (Criza) | Other | Standard of care only This arm will enroll moderate and severe illness patients This arm was ended for all patients per the DSMB in September 2022. |
|
|
| prophylactic heparin | Drug | standard of care dose of heparin |
|
|
| P2Y12 | Drug | added P2Y12 inhibitor |
|
|
| Crizanlizumab Injection | Drug | crizanlizumab injection |
|
| SGLT2 inhibitor | Drug | sglt2 inhibitor |
|
|
| 90 days from enrollment |
| Major Thrombotic Event or in Hospital Death | A composite endpoint of death, pulmonary embolism, systemic arterial thromboembolism, myocardial infarction, or ischemic stroke during hospitalization or at 28 days after enrollment (whichever is earlier) - "major thrombotic events or death" | 28 days |
| Any Thrombotic Event or in Hospital Death | A composite endpoint of death, pulmonary embolism, systemic arterial thromboembolism, myocardial infarction, DVT, or ischemic stroke during hospitalization or at 28 days after enrollment (whichever is earlier) | 28 days |
| Any Renal Replacement Therapy | 28 days |
| Days Free of Organ Support and Renal Replacement Therapy | This outcome variable was designed to exceed day 28 on the IQR. It goes above 28 days because it include baseline day 0 in their design. | 28 days |
| Ventilator Free Days up to Day 28 | This outcome variable was designed to exceed day 28 on the IQR. It goes above 28 days because it include baseline day 0 in their design. | 28 days |
| Days Free of Vasopressors | This outcome variable was designed to exceed day 28 on the IQR. It goes above 28 days because it include baseline day 0 in their design. | 28 days |
| Progression to Intubation or Death | analysis completed on the Heparin protocol | 28 days |
| Survival Until Discharge | 28 days |
| Tucson |
| Arizona |
| 85719 |
| United States |
| University of Arkansas for Medical Sciences | Little Rock | Arkansas | 72205 | United States |
| Kaiser Permanente Fontana | Fontana | California | 92335 | United States |
| Kaiser Permanente Los Angeles | Los Angeles | California | 90027 | United States |
| Smidt Heart Institute at Cedars-Sinai | Los Angeles | California | 90048 | United States |
| Ronald Reagan UCLA Medical Center | Los Angeles | California | 90095 | United States |
| UC San Diego Hillcrest | San Diego | California | 92103 | United States |
| Zuckerberg San Francisco General Hospital | San Francisco | California | 94110 | United States |
| UCSF San Francisco | San Francisco | California | 94143 | United States |
| Zuckerberg San Francisco General Hospital | San Francisco | California | 94410 | United States |
| Stanford University Medical Center | Stanford | California | 94305 | United States |
| Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center | Torrance | California | 90502 | United States |
| Denver Health and Hospital Authority | Denver | Colorado | 80401 | United States |
| St. Mary's Hospital & Regional Medical Center | Grand Junction | Colorado | 81501 | United States |
| Saint Francis Hospital and Medical Center | Hartford | Connecticut | 06105 | United States |
| University of Florida | Gainesville | Florida | 32608 | United States |
| Memorial Hospital | Jacksonville | Florida | 32216 | United States |
| AdventHealth Tampa | Tampa | Florida | 33613 | United States |
| Emory | Atlanta | Georgia | 30308 | United States |
| Morehouse School of Medicine | Atlanta | Georgia | 30310 | United States |
| Queens Medical Center | Honolulu | Hawaii | 96813 | United States |
| Memorial Hospital | Belleville | Illinois | 62226 | United States |
| Cook County Health | Chicago | Illinois | 60612 | United States |
| University of Illinois at Chicago Health (UIH) | Chicago | Illinois | 60612 | United States |
| OSF Little Company of Mary Medical Center (OSF LCM) | Evergreen Park | Illinois | 60805 | United States |
| Indiana University Health Methodist Hospital | Indianapolis | Iowa | 46202 | United States |
| Kansas University Medical Center | Kansas City | Kansas | 66160 | United States |
| Ochsner Clinic Foundation | New Orleans | Louisiana | 70121 | United States |
| Boston University | Boston | Massachusetts | 02118 | United States |
| St Elizabeth's Medical Center | Brighton | Massachusetts | 02135 | United States |
| Baystate Medical Center | Springfield | Massachusetts | 01199 | United States |
| University of Massachusetts | Worcester | Massachusetts | 01655 | United States |
| University of Michigan | Ann Arbor | Michigan | 48109 | United States |
| Wayne State University | Detroit | Michigan | 48201 | United States |
| Hennepin County Medical Center | Minneapolis | Minnesota | 55415 | United States |
| University of Mississippi Medical Center | Jackson | Mississippi | 39216 | United States |
| Washington University School of Medicine, ACCS Research | St Louis | Missouri | 63110 | United States |
| University Medical Center of Southern Nevada | Las Vegas | Nevada | 89102 | United States |
| Cooper Health | Camden | New Jersey | 08103 | United States |
| Englewood Health | Englewood | New Jersey | 07631 | United States |
| Atlantic Health System | Morristown | New Jersey | 07960 | United States |
| Rutgers New Jersey Medical School | Newark | New Jersey | 07103 | United States |
| AtlantiCare Regional Medical Center | Pomona | New Jersey | 08240 | United States |
| Albany Medical College | Albany | New York | 12208 | United States |
| Mercy Hospital Buffalo | Buffalo | New York | 14220 | United States |
| VA New York Harbor Healthcare System | New York | New York | 10010 | United States |
| NYU Langone | New York | New York | 10016 | United States |
| Mt. Sinai Hospital | New York | New York | 10029 | United States |
| SUNY Upstate University Hospital | Syracuse | New York | 13210 | United States |
| Jacobi Medical Center | The Bronx | New York | 10461 | United States |
| Montefiore Medical Center | The Bronx | New York | 10461 | United States |
| Westchester Medical Center | Valhalla | New York | 10595 | United States |
| Duke University Hospital | Durham | North Carolina | 27704 | United States |
| Wake Forest | Winston-Salem | North Carolina | 27157 | United States |
| Cleveland Clinic Akron General | Akron | Ohio | 44307 | United States |
| University of Cincinnati Medical Center | Cincinnati | Ohio | 45219 | United States |
| The MetroHealth System | Cleveland | Ohio | 44109 | United States |
| Cleveland Clinic Foundation | Cleveland | Ohio | 44195 | United States |
| Ohio State Universtiy Wexner Medical Center | Columbus | Ohio | 43210 | United States |
| Mercy Health St Vincent Medical Center | Toledo | Ohio | 43608 | United States |
| Ascension St. John Clinical Research Institute | Tulsa | Oklahoma | 74104 | United States |
| Oregon Health and Science University | Portland | Oregon | 97239 | United States |
| Geisinger Research | Danville | Pennsylvania | 17822 | United States |
| Doylestown Cardiology Associates | Doylestown | Pennsylvania | 18901 | United States |
| Penn State Health Milton S. Hershey Medical Center | Hershey | Pennsylvania | 17033 | United States |
| Hospital of the University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| Temple University | Philadelphia | Pennsylvania | 19141 | United States |
| UPMC Presbyterian | Pittsburgh | Pennsylvania | 15260 | United States |
| Rhode Island Hospital | Providence | Rhode Island | 02903 | United States |
| The Miriam Hospital | Providence | Rhode Island | 02906 | United States |
| Sarah Cannon and HCA Research Institute | Nashville | Tennessee | 37203 | United States |
| Skyline Medical Center | Nashville | Tennessee | 37207 | United States |
| University of Texas at Austin | Austin | Texas | 78701 | United States |
| University of Texas Southwestern Medical Center | Dallas | Texas | 75390 | United States |
| Medical City Ft Worth | Fort Worth | Texas | 76104 | United States |
| Baylor Scott and White Medical Center - Temple | Temple | Texas | 76508 | United States |
| HCA Henrico Doctors Hospital | Richmond | Virginia | 23229 | United States |
| Swedish Hospital | Seattle | Washington | 98122 | United States |
| West Virginia University CTR | Morgantown | West Virginia | 26506 | United States |
| University of Wisconsin Hospital; Meriter Hospital (UW affiliated) | Madison | Wisconsin | 53715 | United States |
| Hospital Universitario Sao Francisco de Assis | Bragança Paulista | Brazil |
| União Brasileira de Educação e Assistência - Hospital São Lucas da PUCRS | Porto Alegre | Brazil |
| Centro de Estudos ClÃnicos do Hospital Cárdio Pulmonar | Salvador | Brazil |
| Fundação Faculdade Regional De Medicina De São José Do Rio Preto | São José do Rio Preto | Brazil |
| Instituto Dante Pazzanese de Cardiologia | São Paulo | Brazil |
| Instituto do Coração do Hospital das ClÃnicas da Faculdade de Medicina da USP-InCor-HCFMUSP | São Paulo | Brazil |
| Azienda Ospedaliero Sant Anna e San Sebastiano | Caserta | Italy |
| Maria Cecilia Hospital , Cotignola, Ravenna | Cotignola | Italy |
| Università degli Studi di Ferrara, Ferrara | Ferrara | Italy |
| Azienda Ospedaliero -Universitaria Careggi | Florence | Italy |
| Policlinico di Napoli, Napoli | Naples | Italy |
| AOU Policlinico di Palermo, Palermo | Palermo | Italy |
| ASL-1 Imperiese, Sanremo | Sanremo | Italy |
| Hospital Universitario A Coruna | A Coruña | Spain |
| Hospital Virgen del Mar | AlmerÃa | Spain |
| Hospital Arnau de Vilanova | Lleida | Spain |
| Hospital Universitario La Paz | Madrid | Spain |
| Hospital Universitario Ramon Y Cajal | Madrid | Spain |
| Hospital ClÃnico Universitario de Salamanca | Salamanca | Spain |
| Hospital ClÃnico Universitario de Santiago de Compostela | Santiago de Compostela | Spain |
| Background |
| Klok FA, Kruip MJHA, van der Meer NJM, Arbous MS, Gommers DAMPJ, Kant KM, Kaptein FHJ, van Paassen J, Stals MAM, Huisman MV, Endeman H. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020 Jul;191:145-147. doi: 10.1016/j.thromres.2020.04.013. Epub 2020 Apr 10. |
| 32369666 | Background | Middeldorp S, Coppens M, van Haaps TF, Foppen M, Vlaar AP, Muller MCA, Bouman CCS, Beenen LFM, Kootte RS, Heijmans J, Smits LP, Bonta PI, van Es N. Incidence of venous thromboembolism in hospitalized patients with COVID-19. J Thromb Haemost. 2020 Aug;18(8):1995-2002. doi: 10.1111/jth.14888. Epub 2020 Jul 27. |
| 32330083 | Background | Poissy J, Goutay J, Caplan M, Parmentier E, Duburcq T, Lassalle F, Jeanpierre E, Rauch A, Labreuche J, Susen S; Lille ICU Haemostasis COVID-19 Group. Pulmonary Embolism in Patients With COVID-19: Awareness of an Increased Prevalence. Circulation. 2020 Jul 14;142(2):184-186. doi: 10.1161/CIRCULATIONAHA.120.047430. Epub 2020 Apr 24. No abstract available. |
| 32171076 | Background | Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11. |
| 32220112 | Background | Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 2020 May;18(5):1094-1099. doi: 10.1111/jth.14817. Epub 2020 Apr 27. |
| 35060325 | Background | Wang L, Zhao L, Li F, Liu J, Zhang L, Li Q, Gu J, Liang S, Zhao Q, Liu J, Xu JF. Risk assessment of venous thromboembolism and bleeding in COVID-19 patients. Clin Respir J. 2022 Mar;16(3):182-189. doi: 10.1111/crj.13467. Epub 2022 Jan 21. |
| 32227120 | Background | Danzi GB, Loffi M, Galeazzi G, Gherbesi E. Acute pulmonary embolism and COVID-19 pneumonia: a random association? Eur Heart J. 2020 May 14;41(19):1858. doi: 10.1093/eurheartj/ehaa254. No abstract available. |
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| 31749809 | Background | Beristain-Covarrubias N, Perez-Toledo M, Thomas MR, Henderson IR, Watson SP, Cunningham AF. Understanding Infection-Induced Thrombosis: Lessons Learned From Animal Models. Front Immunol. 2019 Nov 5;10:2569. doi: 10.3389/fimmu.2019.02569. eCollection 2019. |
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| 16581406 | Background | Smeeth L, Cook C, Thomas S, Hall AJ, Hubbard R, Vallance P. Risk of deep vein thrombosis and pulmonary embolism after acute infection in a community setting. Lancet. 2006 Apr 1;367(9516):1075-1079. doi: 10.1016/S0140-6736(06)68474-2. |
| 20551263 | Background | Harms PW, Schmidt LA, Smith LB, Newton DW, Pletneva MA, Walters LL, Tomlins SA, Fisher-Hubbard A, Napolitano LM, Park PK, Blaivas M, Fantone J, Myers JL, Jentzen JM. Autopsy findings in eight patients with fatal H1N1 influenza. Am J Clin Pathol. 2010 Jul;134(1):27-35. doi: 10.1309/AJCP35KOZSAVNQZW. |
| 29365305 | Background | Kwong JC, Schwartz KL, Campitelli MA, Chung H, Crowcroft NS, Karnauchow T, Katz K, Ko DT, McGeer AJ, McNally D, Richardson DC, Rosella LC, Simor A, Smieja M, Zahariadis G, Gubbay JB. Acute Myocardial Infarction after Laboratory-Confirmed Influenza Infection. N Engl J Med. 2018 Jan 25;378(4):345-353. doi: 10.1056/NEJMoa1702090. |
| 12816821 | Background | Wong RS, Wu A, To KF, Lee N, Lam CW, Wong CK, Chan PK, Ng MH, Yu LM, Hui DS, Tam JS, Cheng G, Sung JJ. Haematological manifestations in patients with severe acute respiratory syndrome: retrospective analysis. BMJ. 2003 Jun 21;326(7403):1358-62. doi: 10.1136/bmj.326.7403.1358. |
| 30477976 | Background | Obi AT, Tignanelli CJ, Jacobs BN, Arya S, Park PK, Wakefield TW, Henke PK, Napolitano LM. Empirical systemic anticoagulation is associated with decreased venous thromboembolism in critically ill influenza A H1N1 acute respiratory distress syndrome patients. J Vasc Surg Venous Lymphat Disord. 2019 May;7(3):317-324. doi: 10.1016/j.jvsv.2018.08.010. Epub 2018 Nov 23. |
| 32766543 | Background | Rapkiewicz AV, Mai X, Carsons SE, Pittaluga S, Kleiner DE, Berger JS, Thomas S, Adler NM, Charytan DM, Gasmi B, Hochman JS, Reynolds HR. Megakaryocytes and platelet-fibrin thrombi characterize multi-organ thrombosis at autopsy in COVID-19: A case series. EClinicalMedicine. 2020 Jun 25;24:100434. doi: 10.1016/j.eclinm.2020.100434. eCollection 2020 Jul. |
| 32343504 | Background | Oxley TJ, Mocco J, Majidi S, Kellner CP, Shoirah H, Singh IP, De Leacy RA, Shigematsu T, Ladner TR, Yaeger KA, Skliut M, Weinberger J, Dangayach NS, Bederson JB, Tuhrim S, Fifi JT. Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young. N Engl J Med. 2020 May 14;382(20):e60. doi: 10.1056/NEJMc2009787. Epub 2020 Apr 28. No abstract available. |
| 32492712 | Background | Al-Samkari H, Karp Leaf RS, Dzik WH, Carlson JCT, Fogerty AE, Waheed A, Goodarzi K, Bendapudi PK, Bornikova L, Gupta S, Leaf DE, Kuter DJ, Rosovsky RP. COVID-19 and coagulation: bleeding and thrombotic manifestations of SARS-CoV-2 infection. Blood. 2020 Jul 23;136(4):489-500. doi: 10.1182/blood.2020006520. |
| Background | Centers for Disease Control and Prevention. COVID-19 in Racial and Ethnic Minority Groups. 2020. |
| 32459916 | Background | Price-Haywood EG, Burton J, Fort D, Seoane L. Hospitalization and Mortality among Black Patients and White Patients with Covid-19. N Engl J Med. 2020 Jun 25;382(26):2534-2543. doi: 10.1056/NEJMsa2011686. Epub 2020 May 27. |
| 32613083 | Background | Aldridge RW, Lewer D, Katikireddi SV, Mathur R, Pathak N, Burns R, Fragaszy EB, Johnson AM, Devakumar D, Abubakar I, Hayward A. Black, Asian and Minority Ethnic groups in England are at increased risk of death from COVID-19: indirect standardisation of NHS mortality data. Wellcome Open Res. 2020 Jun 24;5:88. doi: 10.12688/wellcomeopenres.15922.2. eCollection 2020. |
| 32466757 | Background | Niedzwiedz CL, O'Donnell CA, Jani BD, Demou E, Ho FK, Celis-Morales C, Nicholl BI, Mair FS, Welsh P, Sattar N, Pell JP, Katikireddi SV. Ethnic and socioeconomic differences in SARS-CoV-2 infection: prospective cohort study using UK Biobank. BMC Med. 2020 May 29;18(1):160. doi: 10.1186/s12916-020-01640-8. |
| 32419766 | Background | Millett GA, Jones AT, Benkeser D, Baral S, Mercer L, Beyrer C, Honermann B, Lankiewicz E, Mena L, Crowley JS, Sherwood J, Sullivan PS. Assessing differential impacts of COVID-19 on black communities. Ann Epidemiol. 2020 Jul;47:37-44. doi: 10.1016/j.annepidem.2020.05.003. Epub 2020 May 14. |
| 34934895 | Background | Kamin Mukaz D, Gergi M, Koh I, Zakai NA, Judd SE, Sholzberg M, Baumann Kreuziger L, Freeman K, Colovos C, Olson NC, Cushman M. Thrombo-inflammatory biomarkers and D-dimer in a biracial cohort study. Res Pract Thromb Haemost. 2021 Dec 7;5(8):e12632. doi: 10.1002/rth2.12632. eCollection 2021 Dec. |
| 34302745 | Background | Kosiborod MN, Esterline R, Furtado RHM, Oscarsson J, Gasparyan SB, Koch GG, Martinez F, Mukhtar O, Verma S, Chopra V, Buenconsejo J, Langkilde AM, Ambery P, Tang F, Gosch K, Windsor SL, Akin EE, Soares RVP, Moia DDF, Aboudara M, Hoffmann Filho CR, Feitosa ADM, Fonseca A, Garla V, Gordon RA, Javaheri A, Jaeger CP, Leaes PE, Nassif M, Pursley M, Silveira FS, Barroso WKS, Lazcano Soto JR, Nigro Maia L, Berwanger O. Dapagliflozin in patients with cardiometabolic risk factors hospitalised with COVID-19 (DARE-19): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol. 2021 Sep;9(9):586-594. doi: 10.1016/S2213-8587(21)00180-7. Epub 2021 Jul 21. |
| 34904132 | Background | Leucker TM, Osburn WO, Reventun P, Smith K, Claggett B, Kirwan BA, de Brouwer S, Williams MS, Gerstenblith G, Hager DN, Streiff MB, Solomon SD, Lowenstein CJ. Effect of Crizanlizumab, a P-Selectin Inhibitor, in COVID-19: A Placebo-Controlled, Randomized Trial. JACC Basic Transl Sci. 2021 Dec;6(12):935-945. doi: 10.1016/j.jacbts.2021.09.013. Epub 2021 Dec 8. |
| 34351721 | Background | ATTACC Investigators; ACTIV-4a Investigators; REMAP-CAP Investigators; Lawler PR, Goligher EC, Berger JS, Neal MD, McVerry BJ, Nicolau JC, Gong MN, Carrier M, Rosenson RS, Reynolds HR, Turgeon AF, Escobedo J, Huang DT, Bradbury CA, Houston BL, Kornblith LZ, Kumar A, Kahn SR, Cushman M, McQuilten Z, Slutsky AS, Kim KS, Gordon AC, Kirwan BA, Brooks MM, Higgins AM, Lewis RJ, Lorenzi E, Berry SM, Berry LR, Aday AW, Al-Beidh F, Annane D, Arabi YM, Aryal D, Baumann Kreuziger L, Beane A, Bhimani Z, Bihari S, Billett HH, Bond L, Bonten M, Brunkhorst F, Buxton M, Buzgau A, Castellucci LA, Chekuri S, Chen JT, Cheng AC, Chkhikvadze T, Coiffard B, Costantini TW, de Brouwer S, Derde LPG, Detry MA, Duggal A, Dzavik V, Effron MB, Estcourt LJ, Everett BM, Fergusson DA, Fitzgerald M, Fowler RA, Galanaud JP, Galen BT, Gandotra S, Garcia-Madrona S, Girard TD, Godoy LC, Goodman AL, Goossens H, Green C, Greenstein YY, Gross PL, Hamburg NM, Haniffa R, Hanna G, Hanna N, Hegde SM, Hendrickson CM, Hite RD, Hindenburg AA, Hope AA, Horowitz JM, Horvat CM, Hudock K, Hunt BJ, Husain M, Hyzy RC, Iyer VN, Jacobson JR, Jayakumar D, Keller NM, Khan A, Kim Y, Kindzelski AL, King AJ, Knudson MM, Kornblith AE, Krishnan V, Kutcher ME, Laffan MA, Lamontagne F, Le Gal G, Leeper CM, Leifer ES, Lim G, Lima FG, Linstrum K, Litton E, Lopez-Sendon J, Lopez-Sendon Moreno JL, Lother SA, Malhotra S, Marcos M, Saud Marinez A, Marshall JC, Marten N, Matthay MA, McAuley DF, McDonald EG, McGlothlin A, McGuinness SP, Middeldorp S, Montgomery SK, Moore SC, Morillo Guerrero R, Mouncey PR, Murthy S, Nair GB, Nair R, Nichol AD, Nunez-Garcia B, Pandey A, Park PK, Parke RL, Parker JC, Parnia S, Paul JD, Perez Gonzalez YS, Pompilio M, Prekker ME, Quigley JG, Rost NS, Rowan K, Santos FO, Santos M, Olombrada Santos M, Satterwhite L, Saunders CT, Schutgens REG, Seymour CW, Siegal DM, Silva DG Jr, Shankar-Hari M, Sheehan JP, Singhal AB, Solvason D, Stanworth SJ, Tritschler T, Turner AM, van Bentum-Puijk W, van de Veerdonk FL, van Diepen S, Vazquez-Grande G, Wahid L, Wareham V, Wells BJ, Widmer RJ, Wilson JG, Yuriditsky E, Zampieri FG, Angus DC, McArthur CJ, Webb SA, Farkouh ME, Hochman JS, Zarychanski R. Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19. N Engl J Med. 2021 Aug 26;385(9):790-802. doi: 10.1056/NEJMoa2105911. Epub 2021 Aug 4. |
| 34351722 | Background | REMAP-CAP Investigators; ACTIV-4a Investigators; ATTACC Investigators; Goligher EC, Bradbury CA, McVerry BJ, Lawler PR, Berger JS, Gong MN, Carrier M, Reynolds HR, Kumar A, Turgeon AF, Kornblith LZ, Kahn SR, Marshall JC, Kim KS, Houston BL, Derde LPG, Cushman M, Tritschler T, Angus DC, Godoy LC, McQuilten Z, Kirwan BA, Farkouh ME, Brooks MM, Lewis RJ, Berry LR, Lorenzi E, Gordon AC, Ahuja T, Al-Beidh F, Annane D, Arabi YM, Aryal D, Baumann Kreuziger L, Beane A, Bhimani Z, Bihari S, Billett HH, Bond L, Bonten M, Brunkhorst F, Buxton M, Buzgau A, Castellucci LA, Chekuri S, Chen JT, Cheng AC, Chkhikvadze T, Coiffard B, Contreras A, Costantini TW, de Brouwer S, Detry MA, Duggal A, Dzavik V, Effron MB, Eng HF, Escobedo J, Estcourt LJ, Everett BM, Fergusson DA, Fitzgerald M, Fowler RA, Froess JD, Fu Z, Galanaud JP, Galen BT, Gandotra S, Girard TD, Goodman AL, Goossens H, Green C, Greenstein YY, Gross PL, Haniffa R, Hegde SM, Hendrickson CM, Higgins AM, Hindenburg AA, Hope AA, Horowitz JM, Horvat CM, Huang DT, Hudock K, Hunt BJ, Husain M, Hyzy RC, Jacobson JR, Jayakumar D, Keller NM, Khan A, Kim Y, Kindzelski A, King AJ, Knudson MM, Kornblith AE, Kutcher ME, Laffan MA, Lamontagne F, Le Gal G, Leeper CM, Leifer ES, Lim G, Gallego Lima F, Linstrum K, Litton E, Lopez-Sendon J, Lother SA, Marten N, Saud Marinez A, Martinez M, Mateos Garcia E, Mavromichalis S, McAuley DF, McDonald EG, McGlothlin A, McGuinness SP, Middeldorp S, Montgomery SK, Mouncey PR, Murthy S, Nair GB, Nair R, Nichol AD, Nicolau JC, Nunez-Garcia B, Park JJ, Park PK, Parke RL, Parker JC, Parnia S, Paul JD, Pompilio M, Quigley JG, Rosenson RS, Rost NS, Rowan K, Santos FO, Santos M, Santos MO, Satterwhite L, Saunders CT, Schreiber J, Schutgens REG, Seymour CW, Siegal DM, Silva DG Jr, Singhal AB, Slutsky AS, Solvason D, Stanworth SJ, Turner AM, van Bentum-Puijk W, van de Veerdonk FL, van Diepen S, Vazquez-Grande G, Wahid L, Wareham V, Widmer RJ, Wilson JG, Yuriditsky E, Zhong Y, Berry SM, McArthur CJ, Neal MD, Hochman JS, Webb SA, Zarychanski R. Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19. N Engl J Med. 2021 Aug 26;385(9):777-789. doi: 10.1056/NEJMoa2103417. Epub 2021 Aug 4. |
| 35040887 | Background | Berger JS, Kornblith LZ, Gong MN, Reynolds HR, Cushman M, Cheng Y, McVerry BJ, Kim KS, Lopes RD, Atassi B, Berry S, Bochicchio G, de Oliveira Antunes M, Farkouh ME, Greenstein Y, Hade EM, Hudock K, Hyzy R, Khatri P, Kindzelski A, Kirwan BA, Baumann Kreuziger L, Lawler PR, Leifer E, Lopez-Sendon Moreno J, Lopez-Sendon J, Luther JF, Nigro Maia L, Quigley J, Sherwin R, Wahid L, Wilson J, Hochman JS, Neal MD; ACTIV-4a Investigators. Effect of P2Y12 Inhibitors on Survival Free of Organ Support Among Non-Critically Ill Hospitalized Patients With COVID-19: A Randomized Clinical Trial. JAMA. 2022 Jan 18;327(3):227-236. doi: 10.1001/jama.2021.23605. |
| 42089155 | Derived | Zuchelkowski BE, Inman KW, Nouraie SM, Beru N, Naqvi A, Qin S, Yeh CH, Zhang Y, Shah FA, Sharma L, Dela Cruz CS, Zhang L, McVerry BJ, Morris A, Neal MD, Seheult J, Kitsios GD, Mellors JW, Lawrence DA, Kim PY, Jacobs JL, Bain WG. Soluble Thrombomodulin Links Viremia and Mortality During COVID-19: Results From the ACTIV-4a Trial. J Am Heart Assoc. 2026 May 19;15(10):e047693. doi: 10.1161/JAHA.125.047693. Epub 2026 May 6. |
| 39250922 | Derived | Kosiborod MN, Windsor SL, Vardeny O, Berger JS, Reynolds HR, Boumakis S, Althouse AD, Solomon SD, Bhatt AS, Peikert A, Luther JF, Leifer ES, Kindzelski AL, Cushman M, Ng Gong M, Kornblith LZ, Khatri P, Kim KS, Baumann Kreuziger L, Javaheri A, Carpio C, Wahid L, Lopez-Sendon Moreno J, Alonso A, Ho MQ, Lopez-Sendon J, Lopes RD, Curtis JL, Kirwan BA, Geraci MW, Neal MD, Hochman JS; ACTIV-4a Investigators. Effect of sodium-glucose co-transporter-2 inhibitors on survival free of organ support in patients hospitalised for COVID-19 (ACTIV-4a): a pragmatic, multicentre, open-label, randomised, controlled, platform trial. Lancet Diabetes Endocrinol. 2024 Oct;12(10):725-734. doi: 10.1016/S2213-8587(24)00218-3. Epub 2024 Sep 6. |
| 37979717 | Derived | Greenstein YY, Hubel K, Froess J, Wisniewski SR, Venugopal V, Lai YH, Berger JS, Chang SY, Colovos C, Shah F, Kornblith LZ, Lawler PR, Gaddh M, Guerrero RM, Nkemdirim W, Lopes RD, Reynolds HR, Amigo JS, Wahid L, Zahra A, Goligher EC, Zarychanski R, Leifer E, Huang DT, Neal MD, Hochman JS, Cushman M, Gong MN. Symptoms and Impaired Quality of Life After COVID-19 Hospitalization: Effect of Therapeutic Heparin in Non-ICU Patients in the Accelerating COVID-19 Therapeutic Interventions and Vaccines 4 Acute Trial: Effect on 3-Month Symptoms and Quality of Life. Chest. 2024 Apr;165(4):785-799. doi: 10.1016/j.chest.2023.11.019. Epub 2023 Nov 17. |
| 37489818 | Derived | Fischer AL, Messer S, Riera R, Martimbianco ALC, Stegemann M, Estcourt LJ, Weibel S, Monsef I, Andreas M, Pacheco RL, Skoetz N. Antiplatelet agents for the treatment of adults with COVID-19. Cochrane Database Syst Rev. 2023 Jul 25;7(7):CD015078. doi: 10.1002/14651858.CD015078. |
| 37356038 | Derived | Solomon SD, Lowenstein CJ, Bhatt AS, Peikert A, Vardeny O, Kosiborod MN, Berger JS, Reynolds HR, Mavromichalis S, Barytol A, Althouse AD, Luther JF, Leifer ES, Kindzelski AL, Cushman M, Gong MN, Kornblith LZ, Khatri P, Kim KS, Baumann Kreuziger L, Wahid L, Kirwan BA, Geraci MW, Neal MD, Hochman JS; ACTIV4a Investigators. Effect of the P-Selectin Inhibitor Crizanlizumab on Survival Free of Organ Support in Patients Hospitalized for COVID-19: A Randomized Controlled Trial. Circulation. 2023 Aug;148(5):381-390. doi: 10.1161/CIRCULATIONAHA.123.065190. Epub 2023 Jun 25. |
| 37227729 | Derived | Berger JS, Neal MD, Kornblith LZ, Gong MN, Reynolds HR, Cushman M, Althouse AD, Lawler PR, McVerry BJ, Kim KS, Baumann Kreuziger L, Solomon SD, Kosiborod MN, Berry SM, Bochicchio GV, Contoli M, Farkouh ME, Froess JD, Gandotra S, Greenstein Y, Hade EM, Hanna N, Hudock K, Hyzy RC, Ibanez Estellez F, Iovine N, Khanna AK, Khatri P, Kirwan BA, Kutcher ME, Leifer E, Lim G, Lopes RD, Lopez-Sendon JL, Luther JF, Nigro Maia L, Quigley JG, Wahid L, Wilson JG, Zarychanski R, Kindzelski A, Geraci MW, Hochman JS; ACTIV-4a Investigators. Effect of P2Y12 Inhibitors on Organ Support-Free Survival in Critically Ill Patients Hospitalized for COVID-19: A Randomized Clinical Trial. JAMA Netw Open. 2023 May 1;6(5):e2314428. doi: 10.1001/jamanetworkopen.2023.14428. |
| 36942550 | Derived | Goligher EC, Lawler PR, Jensen TP, Talisa V, Berry LR, Lorenzi E, McVerry BJ, Chang CH, Leifer E, Bradbury C, Berger J, Hunt BJ, Castellucci LA, Kornblith LZ, Gordon AC, McArthur C, Webb S, Hochman J, Neal MD, Zarychanski R, Berry S, Angus DC; REMAP-CAP, ATTACC, and ACTIV-4a Investigators. Heterogeneous Treatment Effects of Therapeutic-Dose Heparin in Patients Hospitalized for COVID-19. JAMA. 2023 Apr 4;329(13):1066-1077. doi: 10.1001/jama.2023.3651. |
| 34473343 | Derived | Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2. |
| 33502773 | Derived | Flumignan RL, Tinoco JDS, Pascoal PI, Areias LL, Cossi MS, Fernandes MI, Costa IK, Souza L, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Prophylactic anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2020 Oct 2;10(10):CD013739. doi: 10.1002/14651858.CD013739. |
| FG001 | Prophylactic Dose Anticoagulation | Heparin standard of care 1.0 - this arm was stopped for all patients in January, 2021 and results are published in PMID: 34351721 (NEJM, August, 2021) (see reference section for citation) prophylactic heparin: standard of care dose of heparin |
| FG002 | Therapeutic Dose Anticoagulation + P2Y12 Inhibitor | increased dose of heparin above standard of care with an added P2Y12 inhibitor This Arm enrolled moderate illness patients only. Enrollment of moderate illness patients in the trial was ended per DSMB on June 19, 2021 and results are published in PMID: PMID: 35040887 (JAMA, January, 2022) (see reference section for citation) theraputic heparin: increased dose of heparin above standard of care. P2Y12: added P2Y12 inhibitor |
| FG003 | Prophylactic Dose Anticoagulation + P2Y12 Inhibitor | Heparin standard of care with an added P2Y12 inhibitor This Arm enrolled severe illness patients only. Enrollment of severe illness patients in the trial was ended per DSMB in June 2022. prophylactic heparin: standard of care dose of heparin P2Y12: added P2Y12 inhibitor |
| FG004 | Standard of Care + SGLT2 Inhibitor | Standard of care plus SGLT2 inhibitor This arm will enroll moderate and severe illness patients This arm was ended in March 2023 SGLT2 inhibitor: sglt2 inhibitor |
| FG005 | Standard of Care (SGLT2) | Standard of care control for the SLGT2 group |
| FG006 | Standard of Care + Crizanlizumab | Standard of care plus crizanlizumab infusion This arm will enroll moderate and severe illness patients This arm was ended for all patients per the DSMB in September 2022. Crizanlizumab Injection: crizanlizumab injection |
| FG007 | Standard of Care (Criza) | Standard of care control for the Criza group |
| COMPLETED |
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| NOT COMPLETED |
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Therapeutic Dose Anticoagulation | increased dose of heparin above standard of care. 1.0 - This arm was stopped in severe patients in December 2020 and results are published in PMID: 34351722 (NEJM, August, 2021) (see reference section for citation). This arm was stopped for moderate patients in January 2021. theraputic heparin: increased dose of heparin above standard of care. |
| BG001 | Prophylactic Dose Anticoagulation | Heparin standard of care 1.0 - this arm was stopped for all patients in January, 2021 and results are published in PMID: 34351721 (NEJM, August, 2021) (see reference section for citation) prophylactic heparin: standard of care dose of heparin |
| BG002 | Therapeutic Dose Anticoagulation + P2Y12 Inhibitor | increased dose of heparin above standard of care with an added P2Y12 inhibitor This Arm enrolled moderate illness patients only. Enrollment of moderate illness patients in the trial was ended per DSMB on June 19, 2021 and results are published in PMID: PMID: 35040887 (JAMA, January, 2022) (see reference section for citation) theraputic heparin: increased dose of heparin above standard of care. P2Y12: added P2Y12 inhibitor |
| BG003 | Prophylactic Dose Anticoagulation + P2Y12 Inhibitor | Heparin standard of care with an added P2Y12 inhibitor This Arm enrolled severe illness patients only. Enrollment of severe illness patients in the trial was ended per DSMB in June 2022. prophylactic heparin: standard of care dose of heparin P2Y12: added P2Y12 inhibitor |
| BG004 | Standard of Care + SGLT2 Inhibitor | Standard of care plus SGLT2 inhibitor This arm will enroll moderate and severe illness patients This arm was ended in March 2023 SGLT2 inhibitor: sglt2 inhibitor |
| BG005 | Standard of Care (SGLT2) | This arm will enroll moderate and severe illness patients This arm was ended in March 2023 |
| BG006 | Standard of Care + Crizanlizumab | Standard of care plus crizanlizumab infusion This arm will enroll moderate and severe illness patients This arm was ended for all patients per the DSMB in September 2022. Crizanlizumab Injection: crizanlizumab injection |
| BG007 | Standard of Care (Criza) | This arm will enroll moderate and severe illness patients This arm was ended for all patients per the DSMB in September 2022. |
| BG008 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 21 Day Organ Support (Respiratory or Vasopressor) Free Days | which is defined as the number of days that a patient is alive and free of organ support through the first 21 days after trial entry. Organ Support is defined as receipt of non-invasive mechanical ventilation, high flow nasal canula oxygen, mechanical ventilation, or vasopressor therapy, with death at any time during the index hospitalization assigned -1 days. This outcome variable was designed to exceed day 21 on the IQR. It goes above 21 days because it include baseline day 0 in their design. | Posted | Median | Inter-Quartile Range | days | 21 days from study enrollment |
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| Secondary | Death Within 28 Days | Numbers are different from participant flow due to missing data. | Posted | Count of Participants | Participants | 28 days from enrollment |
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| Secondary | Acute Kidney Injury | Acute Kidney Injury Acute kidney injury after enrollment is defined by KDIGO criteria for Acute Kidney Injury in the setting of not meeting these criteria upon enrollment: Modified Stages: ∙ Stage 2: Serum Cr 2.0-2.9 times baseline ∙ Stage 3: Serum Cr ≥ 3.0 times baseline, OR Increase in serum creatinine to ≥ 4.0mg/dl, OR Initiation of renal replacement therapy | Analysis was not completed on the Theraputic Dose Anticoagulation or the Prophylactic Dose Anticogulation arms due to not being collected in this protocol. Numbers are different from participant flow due to missing data. | Posted | Count of Participants | Participants | 90 days from enrollment |
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| Secondary | Major Thrombotic Event or in Hospital Death | A composite endpoint of death, pulmonary embolism, systemic arterial thromboembolism, myocardial infarction, or ischemic stroke during hospitalization or at 28 days after enrollment (whichever is earlier) - "major thrombotic events or death" | Numbers are different from participant flow due to missing data. | Posted | Count of Participants | Participants | 28 days |
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| Secondary | Any Thrombotic Event or in Hospital Death | A composite endpoint of death, pulmonary embolism, systemic arterial thromboembolism, myocardial infarction, DVT, or ischemic stroke during hospitalization or at 28 days after enrollment (whichever is earlier) | Numbers are different from participant flow due to missing data. | Posted | Count of Participants | Participants | 28 days |
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| Secondary | Any Renal Replacement Therapy | Numbers are different from participant flow due to missing data. | Posted | Count of Participants | Participants | 28 days |
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| Secondary | Days Free of Organ Support and Renal Replacement Therapy | This outcome variable was designed to exceed day 28 on the IQR. It goes above 28 days because it include baseline day 0 in their design. | Numbers are different from participant flow due to missing data. | Posted | Median | Inter-Quartile Range | days | 28 days |
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| Secondary | Ventilator Free Days up to Day 28 | This outcome variable was designed to exceed day 28 on the IQR. It goes above 28 days because it include baseline day 0 in their design. | Numbers are different from participant flow due to missing data. | Posted | Mean | Inter-Quartile Range | days | 28 days |
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| Secondary | Days Free of Vasopressors | This outcome variable was designed to exceed day 28 on the IQR. It goes above 28 days because it include baseline day 0 in their design. | Numbers are different from participant flow due to missing data. | Posted | Median | Inter-Quartile Range | days | 28 days |
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| Secondary | Progression to Intubation or Death | analysis completed on the Heparin protocol | Numbers are different from participant flow due to missing data. | Posted | Count of Participants | Participants | 28 days |
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| Secondary | Survival Until Discharge | Numbers are different from participant flow due to missing data. | Posted | Count of Participants | Participants | 28 days |
|
Discharge, Death or Day 28
Non Serious adverse events were not collected.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Therapeutic Dose Anticoagulation | increased dose of heparin above standard of care. 1.0 - This arm was stopped in severe patients in December 2020 and results are published in PMID: 34351722 (NEJM, August, 2021) (see reference section for citation). This arm was stopped for moderate patients in January 2021. theraputic heparin: increased dose of heparin above standard of care. | 69 | 569 | 46 | 569 | 0 | 0 |
| EG001 | Prophylactic Dose Anticoagulation | Heparin standard of care 1.0 - this arm was stopped for all patients in January, 2021 and results are published in PMID: 34351721 (NEJM, August, 2021) (see reference section for citation) prophylactic heparin: standard of care dose of heparin | 65 | 514 | 57 | 514 | 0 | 0 |
| EG002 | Therapeutic Dose Anticoagulation + P2Y12 Inhibitor | increased dose of heparin above standard of care with an added P2Y12 inhibitor This Arm enrolled moderate illness patients only. Enrollment of moderate illness patients in the trial was ended per DSMB on June 19, 2021 and results are published in PMID: PMID: 35040887 (JAMA, January, 2022) (see reference section for citation) theraputic heparin: increased dose of heparin above standard of care. P2Y12: added P2Y12 inhibitor | 147 | 772 | 151 | 772 | 0 | 0 |
| EG003 | Prophylactic Dose Anticoagulation + P2Y12 Inhibitor | Heparin standard of care with an added P2Y12 inhibitor This Arm enrolled severe illness patients only. Enrollment of severe illness patients in the trial was ended per DSMB in June 2022. prophylactic heparin: standard of care dose of heparin P2Y12: added P2Y12 inhibitor | 149 | 739 | 133 | 739 | 0 | 0 |
| EG004 | Standard of Care + SGLT2 Inhibitor | Standard of care plus SGLT2 inhibitor This arm will enroll moderate and severe illness patients This arm was ended in March 2023 SGLT2 inhibitor: sglt2 inhibitor | 37 | 287 | 20 | 287 | 0 | 0 |
| EG005 | Standard of Care (sglt2) | Standard of care for sglt2 randomzations This arm will enroll moderate and severe illness patients | 42 | 288 | 33 | 288 | 0 | 0 |
| EG006 | Standard of Care + Crizanlizumab | Standard of care plus crizanlizumab infusion This arm will enroll moderate and severe illness patients This arm was ended for all patients per the DSMB in September 2022. Crizanlizumab Injection: crizanlizumab injection | 37 | 211 | 24 | 211 | 0 | 0 |
| EG007 | Standard of Care (Criza) | Standard of care for criza randomizations This arm will enroll moderate and severe illness patients | 28 | 211 | 28 | 211 | 0 | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Deep Vein Thrombosis | Vascular disorders | Non-systematic Assessment |
| ||
| Pulmonary Embolism | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| myocardial infarction | Cardiac disorders | Non-systematic Assessment |
| ||
| ischemmic stroke | Vascular disorders | Non-systematic Assessment |
| ||
| Other arterial or venous thromboembolism event | Vascular disorders | Non-systematic Assessment |
| ||
| disseminated intravascular coagulation | Vascular disorders | Non-systematic Assessment |
| ||
| symptomatic intracranial or intracerebral hemorrhage | Vascular disorders | Non-systematic Assessment |
| ||
| major bleeding | Vascular disorders | Non-systematic Assessment |
| ||
| heparin induced thrombocytopenia | Injury, poisoning and procedural complications | Non-systematic Assessment |
| ||
| diabetic ketoacidosis | Renal and urinary disorders | Non-systematic Assessment |
| ||
| acute kidney injury | Renal and urinary disorders | Non-systematic Assessment |
| ||
| anaphylaxis | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| pregnancy | Pregnancy, puerperium and perinatal conditions | Non-systematic Assessment |
| ||
| other | Injury, poisoning and procedural complications | Non-systematic Assessment |
| ||
| arterial thromboembolic event | Vascular disorders | Non-systematic Assessment |
| ||
| Venus thrombosis | Vascular disorders | Non-systematic Assessment |
|
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Stephen Wisniewski | University of Pittsburgh | 412-383-4696 | stevewis@pitt.edu |
| Prot_001.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 4, 2021 | Sep 11, 2024 | SAP_003.pdf |
| ICF | No | No | Yes | Informed Consent Form | Oct 22, 2021 | Apr 19, 2023 | ICF_000.pdf |
Not provided
| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D014777 | Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D006493 | Heparin |
| D017984 | Enoxaparin |
| D017985 | Dalteparin |
| D000078222 | Tinzaparin |
| D000077486 | Ticagrelor |
| D000068799 | Prasugrel Hydrochloride |
| D000077144 | Clopidogrel |
| C000614139 | crizanlizumab |
| D000077203 | Sodium-Glucose Transporter 2 Inhibitors |
| C529054 | dapagliflozin |
| C570240 | empagliflozin |
| D000068896 | Canagliflozin |
| C570288 | ertugliflozin |
| ID | Term |
|---|---|
| D006025 | Glycosaminoglycans |
| D011134 | Polysaccharides |
| D002241 | Carbohydrates |
| D006495 | Heparin, Low-Molecular-Weight |
| D000241 | Adenosine |
| D011684 | Purine Nucleosides |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D013988 | Ticlopidine |
| D058924 | Thienopyridines |
| D011725 | Pyridines |
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D007004 | Hypoglycemic Agents |
| D045505 | Physiological Effects of Drugs |
| D005960 | Glucosides |
| D006027 | Glycosides |
Not provided
Not provided
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Brazil |
|
| Italy |
|
| Spain |
|
| Mexico |
|
| Superiority |
| t-test, 2 sided | .6858 | Superiority |
| t-test, 2 sided | .1351 | Superiority |
| OG003 | Prophylactic Dose Anticoagulation + P2Y12 Inhibitor | Heparin standard of care with an added P2Y12 inhibitor This Arm enrolled severe illness patients only. Enrollment of severe illness patients in the trial was ended per DSMB in June 2022. prophylactic heparin: standard of care dose of heparin P2Y12: added P2Y12 inhibitor |
| OG004 | Standard of Care + SGLT2 Inhibitor | Standard of care plus SGLT2 inhibitor This arm will enroll moderate and severe illness patients This arm was ended in March 2023 SGLT2 inhibitor: sglt2 inhibitor |
| OG005 | Standard of Care (SGLT2) | Standard of care control for the SLGT2 group |
| OG006 | Standard of Care + Crizanlizumab | Standard of care plus crizanlizumab infusion This arm will enroll moderate and severe illness patients This arm was ended for all patients per the DSMB in September 2022. Crizanlizumab Injection: crizanlizumab injection |
| OG007 | Standard of Care (Criza) | Standard of care control for the Criza group |
|
|
|
| OG002 |
| Therapeutic Dose Anticoagulation + P2Y12 Inhibitor |
increased dose of heparin above standard of care with an added P2Y12 inhibitor This Arm enrolled moderate illness patients only. Enrollment of moderate illness patients in the trial was ended per DSMB on June 19, 2021 and results are published in PMID: PMID: 35040887 (JAMA, January, 2022) (see reference section for citation) theraputic heparin: increased dose of heparin above standard of care. P2Y12: added P2Y12 inhibitor |
| OG003 | Prophylactic Dose Anticoagulation + P2Y12 Inhibitor | Heparin standard of care with an added P2Y12 inhibitor This Arm enrolled severe illness patients only. Enrollment of severe illness patients in the trial was ended per DSMB in June 2022. prophylactic heparin: standard of care dose of heparin P2Y12: added P2Y12 inhibitor |
| OG004 | Standard of Care + SGLT2 Inhibitor | Standard of care plus SGLT2 inhibitor This arm will enroll moderate and severe illness patients This arm was ended in March 2023 SGLT2 inhibitor: sglt2 inhibitor |
| OG005 | Standard of Care (SGLT2) | Standard of care control for the SLGT2 group |
| OG006 | Standard of Care + Crizanlizumab | Standard of care plus crizanlizumab infusion This arm will enroll moderate and severe illness patients This arm was ended for all patients per the DSMB in September 2022. Crizanlizumab Injection: crizanlizumab injection |
| OG007 | Standard of Care (Criza) | Standard of care control for the Criza group |
|
|
|
| OG003 | Prophylactic Dose Anticoagulation + P2Y12 Inhibitor | Heparin standard of care with an added P2Y12 inhibitor This Arm enrolled severe illness patients only. Enrollment of severe illness patients in the trial was ended per DSMB in June 2022. prophylactic heparin: standard of care dose of heparin P2Y12: added P2Y12 inhibitor |
| OG004 | Standard of Care + SGLT2 Inhibitor | Standard of care plus SGLT2 inhibitor This arm will enroll moderate and severe illness patients This arm was ended in March 2023 SGLT2 inhibitor: sglt2 inhibitor |
| OG005 | Standard of Care (SGLT2) | Standard of care control for the SLGT2 group |
| OG006 | Standard of Care + Crizanlizumab | Standard of care plus crizanlizumab infusion This arm will enroll moderate and severe illness patients This arm was ended for all patients per the DSMB in September 2022. Crizanlizumab Injection: crizanlizumab injection |
| OG007 | Standard of Care (Criza) | Standard of care control for the Criza group |
|
|
|
| OG003 | Prophylactic Dose Anticoagulation + P2Y12 Inhibitor | Heparin standard of care with an added P2Y12 inhibitor This Arm enrolled severe illness patients only. Enrollment of severe illness patients in the trial was ended per DSMB in June 2022. prophylactic heparin: standard of care dose of heparin P2Y12: added P2Y12 inhibitor |
| OG004 | Standard of Care + SGLT2 Inhibitor | Standard of care plus SGLT2 inhibitor This arm will enroll moderate and severe illness patients This arm was ended in March 2023 SGLT2 inhibitor: sglt2 inhibitor |
| OG005 | Standard of Care (SGLT2) | Standard of care control for the SLGT2 group |
| OG006 | Standard of Care + Crizanlizumab | Standard of care plus crizanlizumab infusion This arm will enroll moderate and severe illness patients This arm was ended for all patients per the DSMB in September 2022. Crizanlizumab Injection: crizanlizumab injection |
| OG007 | Standard of Care (Criza) | Standard of care control for the Criza group |
|
|
|
| OG003 | Prophylactic Dose Anticoagulation + P2Y12 Inhibitor | Heparin standard of care with an added P2Y12 inhibitor This Arm enrolled severe illness patients only. Enrollment of severe illness patients in the trial was ended per DSMB in June 2022. prophylactic heparin: standard of care dose of heparin P2Y12: added P2Y12 inhibitor |
| OG004 | Standard of Care + SGLT2 Inhibitor | Standard of care plus SGLT2 inhibitor This arm will enroll moderate and severe illness patients This arm was ended in March 2023 SGLT2 inhibitor: sglt2 inhibitor |
| OG005 | Standard of Care (SGLT2) | Standard of care control for the SLGT2 group |
| OG006 | Standard of Care + Crizanlizumab | Standard of care plus crizanlizumab infusion This arm will enroll moderate and severe illness patients This arm was ended for all patients per the DSMB in September 2022. Crizanlizumab Injection: crizanlizumab injection |
| OG007 | Standard of Care (Criza) | Standard of care control for the Criza group |
|
|
|
| OG003 | Prophylactic Dose Anticoagulation + P2Y12 Inhibitor | Heparin standard of care with an added P2Y12 inhibitor This Arm enrolled severe illness patients only. Enrollment of severe illness patients in the trial was ended per DSMB in June 2022. prophylactic heparin: standard of care dose of heparin P2Y12: added P2Y12 inhibitor |
| OG004 | Standard of Care + SGLT2 Inhibitor | Standard of care plus SGLT2 inhibitor This arm will enroll moderate and severe illness patients This arm was ended in March 2023 SGLT2 inhibitor: sglt2 inhibitor |
| OG005 | Standard of Care (SGLT2) | Standard of care control for the SLGT2 group |
| OG006 | Standard of Care + Crizanlizumab | Standard of care plus crizanlizumab infusion This arm will enroll moderate and severe illness patients This arm was ended for all patients per the DSMB in September 2022. Crizanlizumab Injection: crizanlizumab injection |
| OG007 | Standard of Care (Criza) | Standard of care control for the Criza group |
|
|
|
| OG003 | Prophylactic Dose Anticoagulation + P2Y12 Inhibitor | Heparin standard of care with an added P2Y12 inhibitor This Arm enrolled severe illness patients only. Enrollment of severe illness patients in the trial was ended per DSMB in June 2022. prophylactic heparin: standard of care dose of heparin P2Y12: added P2Y12 inhibitor |
| OG004 | Standard of Care + SGLT2 Inhibitor | Standard of care plus SGLT2 inhibitor This arm will enroll moderate and severe illness patients This arm was ended in March 2023 SGLT2 inhibitor: sglt2 inhibitor |
| OG005 | Standard of Care (SGLT2) | Standard of care control for the SLGT2 group |
| OG006 | Standard of Care + Crizanlizumab | Standard of care plus crizanlizumab infusion This arm will enroll moderate and severe illness patients This arm was ended for all patients per the DSMB in September 2022. Crizanlizumab Injection: crizanlizumab injection |
| OG007 | Standard of Care (Criza) | Standard of care control for the Criza group |
|
|
|
| OG003 | Prophylactic Dose Anticoagulation + P2Y12 Inhibitor | Heparin standard of care with an added P2Y12 inhibitor This Arm enrolled severe illness patients only. Enrollment of severe illness patients in the trial was ended per DSMB in June 2022. prophylactic heparin: standard of care dose of heparin P2Y12: added P2Y12 inhibitor |
| OG004 | Standard of Care + SGLT2 Inhibitor | Standard of care plus SGLT2 inhibitor This arm will enroll moderate and severe illness patients This arm was ended in March 2023 SGLT2 inhibitor: sglt2 inhibitor |
| OG005 | Standard of Care (SGLT2) | Standard of care control for the SLGT2 group |
| OG006 | Standard of Care + Crizanlizumab | Standard of care plus crizanlizumab infusion This arm will enroll moderate and severe illness patients This arm was ended for all patients per the DSMB in September 2022. Crizanlizumab Injection: crizanlizumab injection |
| OG007 | Standard of Care (Criza) | Standard of care control for the Criza group |
|
|
|
| OG003 | Prophylactic Dose Anticoagulation + P2Y12 Inhibitor | Heparin standard of care with an added P2Y12 inhibitor This Arm enrolled severe illness patients only. Enrollment of severe illness patients in the trial was ended per DSMB in June 2022. prophylactic heparin: standard of care dose of heparin P2Y12: added P2Y12 inhibitor |
| OG004 | Standard of Care + SGLT2 Inhibitor | Standard of care plus SGLT2 inhibitor This arm will enroll moderate and severe illness patients This arm was ended in March 2023 SGLT2 inhibitor: sglt2 inhibitor |
| OG005 | Standard of Care (SGLT2) | Standard of care control for the SLGT2 group |
| OG006 | Standard of Care + Crizanlizumab | Standard of care plus crizanlizumab infusion This arm will enroll moderate and severe illness patients This arm was ended for all patients per the DSMB in September 2022. Crizanlizumab Injection: crizanlizumab injection |
| OG007 | Standard of Care (Criza) | Standard of care control for the Criza group |
|
|
|
| OG003 | Prophylactic Dose Anticoagulation + P2Y12 Inhibitor | Heparin standard of care with an added P2Y12 inhibitor This Arm enrolled severe illness patients only. Enrollment of severe illness patients in the trial was ended per DSMB in June 2022. prophylactic heparin: standard of care dose of heparin P2Y12: added P2Y12 inhibitor |
| OG004 | Standard of Care + SGLT2 Inhibitor | Standard of care plus SGLT2 inhibitor This arm will enroll moderate and severe illness patients This arm was ended in March 2023 SGLT2 inhibitor: sglt2 inhibitor |
| OG005 | Standard of Care (SGLT2) | Standard of care control for the SLGT2 group |
| OG006 | Standard of Care + Crizanlizumab | Standard of care plus crizanlizumab infusion This arm will enroll moderate and severe illness patients This arm was ended for all patients per the DSMB in September 2022. Crizanlizumab Injection: crizanlizumab injection |
| OG007 | Standard of Care (Criza) | Standard of care control for the Criza group |
|
|
|