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The researchers wanted to learn how to help sick patients who are in the hospital because of COVID-19. They are trying to find out the best way that is safe to stop blood clots that could be dangerous from forming in patients with COVID-19. This research study happened at 34 hospitals.
All patients in the study took medicines that help prevent blood clots. These medicines are called blood thinners or anticoagulants. Patients got different amounts of blood thinners to see what works better and is safer. Researchers randomly chose some patients to get more and some to get less.
The researchers also wanted to know if another medicine called clopidogrel can safely help stop blood clots from forming. This kind of medicine helps keep parts of the blood, called platelets, from sticking together. In some patients who did not have other reasons to take a platelet-blocker the researchers randomly chose the patient to take clopidogrel or not. This type of medicine is also called an antiplatelet.
This is a multicenter, open-label, randomized-controlled trial in critically-ill patients with novel coronavirus disease 2019 (COVID-19) evaluating the efficacy and safety of full-dose vs. standard prophylactic dose anticoagulation and of antiplatelet vs. no antiplatelet therapy (in a nested second randomization) for prevention of venous and arterial thrombotic events. In a subcohort without an ongoing indication for antiplatelet therapy at screening, the second randomization is performed to either antiplatelet or no antiplatelet therapy
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Full-dose anticoagulation (FDAC) | Experimental |
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| Standard-dose prophylactic anticoagulation (SDPAC) | Active Comparator |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Unfractionated Heparin IV | Drug | Unfractionated heparin (UFH) administered intravenously with a nomogram targeting an aPTT of 1.5-2.5 times the control as per institutional therapeutic target for treatment of VTE |
| Measure | Description | Time Frame |
|---|---|---|
| Venous or Arterial Thrombotic Events: Full-dose Anticoagulation Versus Standard-dose Prophylactic Anticoagulation | The efficacy of these interventions was analyzed using an unmatched win ratio.
| 28 days or until hospital discharge, whichever earlier |
| Venous or Arterial Thrombotic Events: Anti-platelet Therapy Versus No Anti-platelet Therapy | The efficacy of these interventions was analyzed using an unmatched win ratio.
| 28 days or until hospital discharge, whichever earlier |
| Measure | Description | Time Frame |
|---|---|---|
| Clinically Evident Venous or Arterial Thrombotic Events: Full-dose Anticoagulation Versus Standard-dose Prophylactic Anticoagulation | The efficacy of these interventions was analyzed using an unmatched win ratio.
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Inclusion Criteria:
Key Exclusion Criteria:
Ongoing (>48 hours) or planned full-dose (therapeutic) anticoagulation for any indication
Ongoing or planned treatment with dual antiplatelet therapy
Contraindication to antithrombotic therapy or high risk of bleeding due to conditions including, but not limited to, any of the following:
History of heparin-induced thrombocytopenia
Ischemic stroke within the past 2 weeks
Patients who meet the following criterion are excluded from the second randomization (antiplatelet therapy vs. no antiplatelet therapy):
1. Ongoing or planned antiplatelet therapy, including aspirin monotherapy
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| Name | Affiliation | Role |
|---|---|---|
| Marc S Sabatine, MD, MPH | The TIMI Study Group | Study Chair |
| David A Morrow, MD, MPH | The TIMI Study Group | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Brigham and Women's Hospital | Boston | Massachusetts | 02459 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36036760 | Result | Bohula EA, Berg DD, Lopes MS, Connors JM, Babar I, Barnett CF, Chaudhry SP, Chopra A, Ginete W, Ieong MH, Katz JN, Kim EY, Kuder JF, Mazza E, McLean D, Mosier JM, Moskowitz A, Murphy SA, O'Donoghue ML, Park JG, Prasad R, Ruff CT, Shahrour MN, Sinha SS, Wiviott SD, Van Diepen S, Zainea M, Baird-Zars V, Sabatine MS, Morrow DA; COVID-PACT Investigators. Anticoagulation and Antiplatelet Therapy for Prevention of Venous and Arterial Thrombotic Events in Critically Ill Patients With COVID-19: COVID-PACT. Circulation. 2022 Nov;146(18):1344-1356. doi: 10.1161/CIRCULATIONAHA.122.061533. Epub 2022 Aug 29. | |
| 37489818 |
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Patients were randomized in a 1:1 allocation ratio to receive either full-dose anticoagulation (FDAC) or standard-dose prophylactic anticoagulation (SDPAC). In a subset of patients without an ongoing indication for antiplatelet (AP) therapy at baseline, a second randomization was performed in a 1:1 allocation ratio to either AP or no AP therapy. Analyses of anticoagulation were pooled across AP regimens, and AP therapy vs. no AP therapy were pooled across anticoagulant regimens.
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| ID | Title | Description |
|---|---|---|
| FG000 | Full-dose Anticoagulation (FDAC) |
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| 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_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 28, 2020 |
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Randomized-controlled trial - 1) full-dose anticoagulation (FDAC) versus standard-dose prophylactic anticoagulation (SDPAC) (pooled across antiplatelet regimens) and in a subset of patients 2) antiplatelet (AP) versus no AP therapy (pooled across anticoagulant regimens)
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| Enoxaparin 1 mg/kg | Drug | Enoxaparin 1 mg/kg administered subcutaneously (SC) every 12 hours |
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| Clopidogrel | Drug | Clopidogrel 300 mg administered once orally on the day of randomization, followed by 75 mg administered once daily orally on subsequent days |
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| Unfractionated heparin SC | Drug | Heparin 5,000 units administered subcutaneous three times daily |
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| Enoxaparin 40 mg SC | Drug | Enoxaparin 40 mg administered subcutaneously (SC) once daily (reduce to 30 mg if CrCl<30 ml/min) |
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| 28 days or until hospital discharge, whichever earlier |
| Clinically Evident Venous or Arterial Thrombotic Events: Anti-platelet Therapy Versus No Anti-platelet Therapy | The efficacy of these interventions was analyzed using an unmatched win ratio.
| 28 days or until hospital discharge, whichever earlier |
| 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. |
| 35474746 | Derived | Lee CK, Merriam LT, Pearson JC, Lipnick MS, McKleroy W, Kim EY. Treating COVID-19: Evolving approaches to evidence in a pandemic. Cell Rep Med. 2022 Feb 9;3(3):100533. doi: 10.1016/j.xcrm.2022.100533. eCollection 2022 Mar 15. |
| 35244208 | Derived | Flumignan RL, Civile VT, Tinoco JDS, Pascoal PI, Areias LL, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Anticoagulants for people hospitalised with COVID-19: a rapid review. Cochrane Database Syst Rev. 2022 Mar 4;3(3):CD013739. doi: 10.1002/14651858.CD013739.pub2. |
| FG001 | Standard-dose Prophylactic Anticoagulation (SDPAC) |
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| Randomized to Anti-platelet Therapy |
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| Randomized to no Antiplatelet Therapy |
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| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Full-dose Anticoagulation (FDAC) |
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| BG001 | Standard-dose Prophylactic Anticoagulation (SDPAC) |
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| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Inter-Quartile Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| 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 | Venous or Arterial Thrombotic Events: Full-dose Anticoagulation Versus Standard-dose Prophylactic Anticoagulation | The efficacy of these interventions was analyzed using an unmatched win ratio.
| The on-treatment analysis population, consisting of all randomly assigned patients who received at least 1 dose of the randomly allocated study strategy. As is pre-specified in the Study Protocol, comparisons between FDAC and SDPAC are reported irrespective of whether participants received anti-platelet therapy. | Posted | Number | Number of wins | 28 days or until hospital discharge, whichever earlier |
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| Secondary | Clinically Evident Venous or Arterial Thrombotic Events: Full-dose Anticoagulation Versus Standard-dose Prophylactic Anticoagulation | The efficacy of these interventions was analyzed using an unmatched win ratio.
| The on-treatment analysis population, consisting of all randomly assigned patients who received at least 1 dose of the randomly allocated study strategy. The on-treatment analysis population, consisting of all randomly assigned patients who received at least 1 dose of the randomly allocated study strategy. As is pre-specified in the Study Protocol, comparisons between FDAC and SDPAC are reported irrespective of whether participants received anti-platelet therapy. | Posted | Number | Number of wins | 28 days or until hospital discharge, whichever earlier |
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| Primary | Venous or Arterial Thrombotic Events: Anti-platelet Therapy Versus No Anti-platelet Therapy | The efficacy of these interventions was analyzed using an unmatched win ratio.
| The on-treatment analysis population, consisting of all randomly assigned patients who received at least 1 dose of the randomly allocated study strategy. As is pre-specified in the Study Protocol, comparisons between anti-platelet therapy and no anti-platelet therapy are reported irrespective of which anticoagulation intervention participants received. | Posted | Number | Number of wins | 28 days or until hospital discharge, whichever earlier |
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| Secondary | Clinically Evident Venous or Arterial Thrombotic Events: Anti-platelet Therapy Versus No Anti-platelet Therapy | The efficacy of these interventions was analyzed using an unmatched win ratio.
| The on-treatment analysis population, consisting of all randomly assigned patients who received at least 1 dose of the randomly allocated study strategy. As is pre-specified in the Study Protocol, comparisons between anti-platelet therapy and no anti-platelet therapy are reported irrespective of which anticoagulation intervention participants received. | Posted | Number | Number of wins | 28 days or until hospital discharge, whichever earlier |
|
28 days or until hospital discharge, whichever earlier
Investigators are required to report: (1) Serious Adverse Events Related to Study Drug, (2) Unexpected Problems, and (3) Adverse Events Leading to Drug Discontinuation.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Full-dose Anticoagulation (FDAC) |
| 55 | 197 | 16 | 197 | 37 | 197 |
| EG001 | Standard-dose Prophylactic Anticoagulation (SDPAC) |
| 62 | 193 | 3 | 193 | 22 | 193 |
| EG002 | Antiplatelet Therapy | Clopidogrel 300 mg administered once orally on the day of randomization, followed by 75 mg administered once daily on subsequent days. | 41 | 152 | 6 | 152 | 25 | 152 |
| EG003 | No Anti-platelet Therapy | Participants did not receive anti-platelet therapy. | 34 | 140 | 0 | 140 | 0 | 140 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute Enteritis | Gastrointestinal disorders | Systematic Assessment |
| ||
| Acute Renal Failure | Renal and urinary disorders | Systematic Assessment |
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| Acute Respiratory Failure | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Compartment Syndrome Left Arm | General disorders | Systematic Assessment |
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| Deep Venous Thrombosis | Vascular disorders | Systematic Assessment |
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| Drug Induced Thrombocytopenia | Blood and lymphatic system disorders | Systematic Assessment |
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| Gastrointestinal bleed | General disorders | Systematic Assessment |
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| Gross Hematuria | General disorders | Systematic Assessment |
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| Hematemesis | General disorders | Systematic Assessment |
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| Intracranial Hemmorrhage | General disorders | Systematic Assessment |
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| Lower Respiratory Tract Bleed | General disorders | Systematic Assessment |
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| Pulmonary bleeding from left upper lobe | General disorders | Systematic Assessment |
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| Rectus Sheath Hematoma | General disorders | Systematic Assessment |
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| Retroperitoneal Bleed | General disorders | Systematic Assessment |
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| Retroperitoneal hematoma | General disorders | Systematic Assessment |
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| Right Rectus Intramuscular Hematoma | General disorders | Systematic Assessment |
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| Right upper extremity soft tissue hematoma | General disorders | Systematic Assessment |
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| Right wrist intramural hematoma | General disorders | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bleeding | General disorders | Systematic Assessment |
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| Venous thromboembolism | Vascular disorders | Systematic Assessment |
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| D-dimer elevation | Blood and lymphatic system disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| COVID-PACT Project Manager | Brigham and Women's Hospital | (617) 278-0145 | covid-pact@bwh.harvard.edu |
| Apr 27, 2023 |
| Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| D054556 | Venous Thromboembolism |
| 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 |
| D013923 | Thromboembolism |
| D016769 | Embolism and Thrombosis |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D017984 | Enoxaparin |
| D000077144 | Clopidogrel |
| ID | Term |
|---|---|
| D006495 | Heparin, Low-Molecular-Weight |
| D006493 | Heparin |
| D006025 | Glycosaminoglycans |
| D011134 | Polysaccharides |
| D002241 | Carbohydrates |
| D013988 | Ticlopidine |
| D058924 | Thienopyridines |
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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| Male |
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| Non-white |
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| OG001 | Prophylactic Anticoagulation |
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| OG001 | No Anti-platelet Therapy | Participants did not receive anti-platelet therapy. Received either FDAC( Unfractionated heparin (UFH) administered intravenously with a nomogram targeting an aPTT of 1.5-2.5 times the control as per institutional therapeutic target for treatment of VTE; or Enoxaparin 1 mg/kg administered subcutaneously (SC) every 12 hours) or SDPAC (Enoxaparin 40 mg administered SC once daily (reduce to 30 mg if CrCl<30 ml/min)*; or Heparin 5,000 units administered SC three times daily). |
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| OG001 | No Anti-platelet Therapy | Participants did not receive anti-platelet therapy. Received either FDAC( Unfractionated heparin (UFH) administered intravenously with a nomogram targeting an aPTT of 1.5-2.5 times the control as per institutional therapeutic target for treatment of VTE; or Enoxaparin 1 mg/kg administered subcutaneously (SC) every 12 hours) or SDPAC (Enoxaparin 40 mg administered SC once daily (reduce to 30 mg if CrCl<30 ml/min)*; or Heparin 5,000 units administered SC three times daily). |
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