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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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ORCHID is a multicenter, blinded, placebo-controlled, randomized clinical trial evaluating hydroxychloroquine for the treatment of adults hospitalized with COVID-19. Patients, treating clinicians, and study personnel will all be blinded to study group assignment.
Effective therapies for COVID-19 are urgently needed. Hydroxychloroquine is an antimicrobial agent with immunomodulatory and antiviral properties that has demonstrated in vitro activity against SARS-CoV-2, the virus that causes COVID-19. Preliminary reports suggest potential efficacy in small human studies. Clinical trial data are needed to determine whether hydroxychloroquine is effective in treating COVID-19.
Study Aim: To compare the effect of hydroxychloroquine versus placebo on clinical outcomes, measured using the COVID Ordinal Outcomes Scale at Day 15, among adults with COVID-19 requiring hospitalization.
Study Hypothesis: Among adults hospitalized with COVID-19, administration of hydroxychloroquine will improve clinical outcomes at Day 15.
.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Hydroxychlorquine | Active Comparator | Participants assigned to the hydroxychloroquine arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. |
|
| Placebo | Placebo Comparator | Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hydroxychloroquine | Drug | Hydroxychloroquine is available in 200 mg oral tablets of hydroxychloroquine sulfate. For this COVID-19 trial, we will use an oral or enteral dose of hydroxychloroquine 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. |
| Measure | Description | Time Frame |
|---|---|---|
| COVID Outcomes Scale Score on Study Day 15 (14 Days After Randomization) | We will determine the COVID Ordinal Scale for all patients on study day 15 COVID Ordinal Scale defined as:
| Assessed on study day 15 |
| Measure | Description | Time Frame |
|---|---|---|
| COVID Ordinal Outcomes Scale on Study Day 3 (2 Days After Randomization) | We will determine the COVID Ordinal Scale for all patients on study day 3 COVID Ordinal Scale defined as:
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients With Seizures to Day 28 | We will determine the number of patients that experience seizure between randomization and day 28 | 28 days after randomization |
| Number of Patients With Atrial Arrhythmia to Day 28 |
Inclusion Criteria:
Age ≥18 years
Currently hospitalized or in an emergency department with anticipated hospitalization.
Symptoms of acute respiratory infection, defined as one or more of the following:
Laboratory-confirmed SARS-CoV-2 infection within the past 10 days prior to randomization.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Boyd Taylor Thompson, MD | Massachusetts General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Arizona | Tucson | Arizona | 85721 | United States | ||
| UCSF Fresno |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33165621 | Derived | Self WH, Semler MW, Leither LM, Casey JD, Angus DC, Brower RG, Chang SY, Collins SP, Eppensteiner JC, Filbin MR, Files DC, Gibbs KW, Ginde AA, Gong MN, Harrell FE Jr, Hayden DL, Hough CL, Johnson NJ, Khan A, Lindsell CJ, Matthay MA, Moss M, Park PK, Rice TW, Robinson BRH, Schoenfeld DA, Shapiro NI, Steingrub JS, Ulysse CA, Weissman A, Yealy DM, Thompson BT, Brown SM; National Heart, Lung, and Blood Institute PETAL Clinical Trials Network; Steingrub J, Smithline H, Tiru B, Tidswell M, Kozikowski L, Thornton-Thompson S, De Souza L, Hou P, Baron R, Massaro A, Aisiku I, Fredenburgh L, Seethala R, Johnsky L, Riker R, Seder D, May T, Baumann M, Eldridge A, Lord C, Shapiro N, Talmor D, O'Mara T, Kirk C, Harrison K, Kurt L, Schermerhorn M, Banner-Goodspeed V, Boyle K, Dubosh N, Filbin M, Hibbert K, Parry B, Lavin-Parsons K, Pulido N, Lilley B, Lodenstein C, Margolin J, Brait K, Jones A, Galbraith J, Peacock R, Nandi U, Wachs T, Matthay M, Liu K, Kangelaris K, Wang R, Calfee C, Yee K, Hendey G, Chang S, Lim G, Qadir N, Tam A, Beutler R, Levitt J, Wilson J, Rogers A, Vojnik R, Roque J, Albertson T, Chenoweth J, Adams J, Pearson S, Juarez M, Almasri E, Fayed M, Hughes A, Hillard S, Huebinger R, Wang H, Vidales E, Patel B, Ginde A, Moss M, Baduashvili A, McKeehan J, Finck L, Higgins C, Howell M, Douglas I, Haukoos J, Hiller T, Lyle C, Cupelo A, Caruso E, Camacho C, Gravitz S, Finigan J, Griesmer C, Park P, Hyzy R, Nelson K, McDonough K, Olbrich N, Williams M, Kapoor R, Nash J, Willig M, Ford H, Gardner-Gray J, Ramesh M, Moses M, Ng Gong M, Aboodi M, Asghar A, Amosu O, Torres M, Kaur S, Chen JT, Hope A, Lopez B, Rosales K, Young You J, Mosier J, Hypes C, Natt B, Borg B, Salvagio Campbell E, Hite RD, Hudock K, Cresie A, Alhasan F, Gomez-Arroyo J, Duggal A, Mehkri O, Hastings A, Sahoo D, Abi Fadel F, Gole S, Shaner V, Wimer A, Meli Y, King A, Terndrup T, Exline M, Pannu S, Robart E, Karow S, Hough C, Robinson B, Johnson N, Henning D, Campo M, Gundel S, Seghal S, Katsandres S, Dean S, Khan A, Krol O, Jouzestani M, Huynh P, Weissman A, Yealy D, Scholl D, Adams P, McVerry B, Huang D, Angus D, Schooler J, Moore S, Files C, Miller C, Gibbs K, LaRose M, Flores L, Koehler L, Morse C, Sanders J, Langford C, Nanney K, MdalaGausi M, Yeboah P, Morris P, Sturgill J, Seif S, Cassity E, Dhar S, de Wit M, Mason J, Goodwin A, Hall G, Grady A, Chamberlain A, Brown S, Bledsoe J, Leither L, Peltan I, Starr N, Fergus M, Aston V, Montgomery Q, Smith R, Merrill M, Brown K, Armbruster B, Harris E, Middleton E, Paine R, Johnson S, Barrios M, Eppensteiner J, Limkakeng A, McGowan L, Porter T, Bouffler A, Leahy JC, deBoisblanc B, Lammi M, Happel K, Lauto P, Self W, Casey J, Semler M, Collins S, Harrell F, Lindsell C, Rice T, Stubblefield W, Gray C, Johnson J, Roth M, Hays M, Torr D, Zakaria A, Schoenfeld D, Thompson T, Hayden D, Ringwood N, Oldmixon C, Ulysse C, Morse R, Muzikansky A, Fitzgerald L, Whitaker S, Lagakos A, Brower R, Reineck L, Aggarwal N, Bienstock K, Freemer M, Maclawiw M, Weinmann G, Morrison L, Gillespie M, Kryscio R, Brodie D, Zareba W, Rompalo A, Boeckh M, Parsons P, Christie J, Hall J, Horton N, Zoloth L, Dickert N, Diercks D. Effect of Hydroxychloroquine on Clinical Status at 14 Days in Hospitalized Patients With COVID-19: A Randomized Clinical Trial. JAMA. 2020 Dec 1;324(21):2165-2176. doi: 10.1001/jama.2020.22240. |
| Label | URL |
|---|---|
| Website for the PETAL Network | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Hydroxychloroquine | Participants assigned to the hydroxychloroquine arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. Hydroxychloroquine: Hydroxychloroquine is available in 200 mg oral tablets of hydroxychloroquine sulfate. For this COVID-19 trial, we will use an oral or enteral dose of hydroxychloroquine 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. |
| 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 | Jun 4, 2020 | Dec 1, 2020 |
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Eligible participants will be randomized 1:1 to hydroxychloroquine versus placebo. Randomization will be stratified by site and be in permuted blocks of variable size.
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Patients, treating clinicians, trial personnel, and outcome assessors will be blinded to group assignment.
|
| Placebo | Drug | Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. |
|
| assessed on study day 3 |
| COVID Ordinal Outcomes Scale on Study Day 8 (7 Days After Randomization) | We will determine the COVID Ordinal Scale on study day 8 COVID Ordinal Scale defined as:
| assessed on study day 8 |
| COVID Ordinal Outcomes Scale on Study Day 29 (28 Days After Randomization) | We will determine the COVID Ordinal Scale on study day 29 COVID Ordinal Scale defined as:
| assessed on study day 29 |
| All-location, All-cause Mortality Assessed on Study Day 15 (14 Days After Randomization) | Vital status of the patient on day 15 will be determined using any of the following methods: medical record review, phone calls to patient or proxy. There were two patients for whom we were unable to collect their vital status. | assessed on study day 15 |
| All-location, All-cause Mortality Assessed on Study Day 29 (28 Days After Randomization) | Vital status of the patient at day 28 will be determined using any of the following methods: medical record review, phone calls to patient or proxy. There were two patients for whom we were unable to collect their vital status. | assessed on study day 29 |
| Number of Patients Dead or With Receipt of ECMO Between Enrollment and Day 28 | We will determine the number of patients who are either dead or on ECMO ( extracorporeal membrane oxygenation) between enrollment and day 28 | Enrollment to Day 28 |
| Oxygen-free Days Through Day 28 | The number of calendar days between randomization and 28 days later that the patient is alive and without the use of oxygen therapy. Patients who die prior to day 28 are assigned zero oxygen free days. | 28 days after randomization |
| Ventilator-free Days Through Day 28 | Ventilator-free days is defined to be 28 days minus the duration of mechanical ventilation through day 28. Participants who do not survive to day 28 are assigned zero ventilator-free days. | 28 days after randomization |
| Vasopressor-free Days Through Day 28 | The number of calendar days between randomization and 28 days later that the patient is alive and without the use of vasopressor therapy. Patients who die prior to day 28 are assigned zero vasopressor free days. | 28 days after randomization |
| ICU-free Days to Day 28 | The number of days spent out of the ICU to day 28. Patients who die prior to day 28 are assigned zero ICU free days. | 28 days after randomization |
| Hospital-free Days to Day 28 | Defined as 28 days minus the number of days from randomization to discharge home.If a patient has not been discharged home prior to day 28 or dies prior to day 28, hospital free days will be zero. | 28 days after randomization |
We will determine the number of patients that experience atrial arrhythmia between randomization and day 28
| 28 days after randomization |
| Number of Patients With Ventricular Arrhythmia to Day 28 | We will determine the number of patients that experience ventricular arrhythmia between randomization and day 28 | 28 days after randomization |
| Number of Patients With Cardiac Arrest to Day 28 | We will determine the number of patients that experience cardiac arrest between randomization and day 28 | 28 days after randomization |
| Number of Patients With Elevation in Aspartate Aminotransferase or Alanine Aminotransferase to Twice the Local Upper Limit of Normal to Day 28 | We will determine the number of patients that experience elevation in aspartate aminotransferase or alanine aminotransferase to twice the local upper limit of normal between randomization and day 28 | 28 days after randomization |
| Number of Patients With Acute Pancreatitis Arrest to Day 28 | We will determine the number of patients that experience acute pancreatitis between randomization and day 28 | 28 days after randomization |
| Number of Patients With Acute Kidney Injury to day28 | We will determine the number of patients that experience acute kidney injury between randomization and day 28 | 28 days after randomization |
| Number of Patients With Receipt of Renal Replacement Therapy to Day 28 | We will determine the number of patients that experience renal replacement therapy between randomization and day 28 | 28 days after randomization |
| Number of Patients With Symptomatic Hypoglycemia to Day 28 | We will determine the number of patients that experience symptomatic hypoglycemia between randomization and day 28 | 28 days after randomization |
| Number of Patients With Neutropenia to Day 28 | We will determine the number of patients that experience neutropenia between randomization and day 28 | 28 days after randomization |
| Number of Patients With Lymphopenia to Day 28 | We will determine the number of patients that experience lymphopenia between randomization and day 28 | 28 days after randomization |
| Number of Patients With Anemia to Day 28 | We will determine the number of patients that experience anemia between randomization and day 28 | 28 days after randomization |
| Number of Patients With Thrombocytopenia to Day 28 | We will determine the number of patients that experience thrombocytopenia between randomization and day 28 | 28 days after randomization |
| Number of Patients With Severe Dermatologic Reaction to Day 28 | We will determine the number of patients that experience severe dermatologic reaction between randomization and day 28 | 28 days after randomization |
| Time to Recovery, Defined as Time to Reaching Level 5, 6, or 7 on the COVID Outcomes Scale, Which is the Time to the Earlier of Final Liberation From Supplemental Oxygen or Hospital Discharge | Time to recovery, defined as time to reaching level 5, 6, or 7 on the COVID Outcomes Scale, which is the time to the earlier of final liberation from supplemental oxygen or hospital discharge. Patients who die prior to day 28 are assigned 28 days for time to recovery. | 28 days after randomization |
| Fresno |
| California |
| 93701 |
| United States |
| Ronald Reagan UCLA Medical Center | Los Angeles | California | 90095 | United States |
| UC Davis Medical Center | Sacramento | California | 95817 | United States |
| UCSF Medical Center | San Francisco | California | 94143 | United States |
| Stanford University | Stanford | California | 94305 | United States |
| Medical Center of Aurora | Aurora | Colorado | 80045 | United States |
| University of Colorado Hospital | Aurora | Colorado | 80045 | United States |
| Denver Health Medical Center | Denver | Colorado | 80204 | United States |
| St. Joseph Hospital | Denver | Colorado | 80218 | United States |
| University of Florida | Gainesville | Florida | 32608 | United States |
| University of Kentucky | Lexington | Kentucky | 40506 | United States |
| University Medical Center | New Orleans | Louisiana | 70112 | United States |
| Maine Medical Center | Portland | Maine | 04102 | United States |
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| Beth Israel Deaconess Medical Center | Boston | Massachusetts | 02115 | United States |
| Brigham and Women's Hospital | Boston | Massachusetts | 02445 | United States |
| Baystate Medical Center | Springfield | Massachusetts | 01199 | United States |
| St. Vincent's Hospital | Worcester | Massachusetts | 01608 | United States |
| University of Michigan Medical Center | Ann Arbor | Michigan | 48109 | United States |
| Henry Ford Medical Center | Detroit | Michigan | 48025 | United States |
| University of Mississippi Medical Center | Jackson | Mississippi | 39216 | United States |
| Montefiore Medical Center-Weiler | The Bronx | New York | 10461 | United States |
| Montefiore Medical Center-Moses | The Bronx | New York | 10467 | United States |
| Wake Forest Baptist Medical Center | Winston-Salem | North Carolina | 27157 | United States |
| University of Cincinnati Medical Center | Cincinnati | Ohio | 45219 | United States |
| Cleveland Clinic Foundation | Cleveland | Ohio | 44195 | United States |
| Ohio State University Wexner Medical Center | Columbus | Ohio | 43210 | United States |
| Oregon Health and Science University | Portland | Oregon | 97239 | United States |
| Penn State Hershey Medical Center | Hershey | Pennsylvania | 17033 | United States |
| Temple University Hospital | Philadelphia | Pennsylvania | 19140 | United States |
| UPMC Presbyterian/Mercy/Shadyside | Pittsburgh | Pennsylvania | 15261 | United States |
| Medical University of South Carolina | Charleston | South Carolina | 29425 | United States |
| Vanderbilt University Medical Center | Nashville | Tennessee | 37221 | United States |
| University of Texas Health Science Center | Houston | Texas | 77030 | United States |
| Intermountain Medical Center | Murray | Utah | 84107 | United States |
| University of Utah Hospital | Salt Lake City | Utah | 84132 | United States |
| VCU Medical Center | Richmond | Virginia | 23298 | United States |
| Harborview Medical Center | Seattle | Washington | 98104 | United States |
| Swedish Hospital First Hill | Seattle | Washington | 98122 | United States |
| 32492354 | Derived | Casey JD, Johnson NJ, Semler MW, Collins SP, Aggarwal NR, Brower RG, Chang SY, Eppensteiner J, Filbin M, Gibbs KW, Ginde AA, Gong MN, Harrell F, Hayden DL, Hough CL, Khan A, Leither LM, Moss M, Oldmixon CF, Park PK, Reineck LA, Ringwood NJ, Robinson BRH, Schoenfeld DA, Shapiro NI, Steingrub JS, Torr DK, Weissman A, Lindsell CJ, Rice TW, Thompson BT, Brown SM, Self WH. Rationale and Design of ORCHID: A Randomized Placebo-controlled Clinical Trial of Hydroxychloroquine for Adults Hospitalized with COVID-19. Ann Am Thorac Soc. 2020 Sep;17(9):1144-1153. doi: 10.1513/AnnalsATS.202005-478SD. |
| FG001 | Placebo | Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. Placebo: Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. |
| COMPLETED |
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| NOT COMPLETED |
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Hydroxychloroquine | Participants assigned to the hydroxychloroquine arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. Hydroxychloroquine: Hydroxychloroquine is available in 200 mg oral tablets of hydroxychloroquine sulfate. For this COVID-19 trial, we will use an oral or enteral dose of hydroxychloroquine 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. |
| BG001 | Placebo | Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. Placebo: Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. |
| BG002 | 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, Continuous | Median | Inter-Quartile Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | This measure was analyzed in participants with available data on race and ethnicity. | Count of Participants | Participants |
| |||||||||||||||
| Living at home in the community prior to hospitalization | Count of Participants | Participants |
| ||||||||||||||||
| Body mass index | This measure was analyzed in participants with available data on body mass index | Median | Inter-Quartile Range | kg/m^2 |
| ||||||||||||||
| Chronic Conditions | Count of Participants | Participants |
| ||||||||||||||||
| Location at time of randomization | Measure was analyzed in participants with available data on location at time of randomization. | Count of Participants | Participants |
| |||||||||||||||
| Symptoms of acute respiratory infection | Count of Participants | Participants |
| ||||||||||||||||
| Duration of symptoms prior to randomization | Median | Inter-Quartile Range | days |
| |||||||||||||||
| Time between hospital presentation and randomization | Defined as the time of the first contact with an acute care hospital during the health care episode that resulted in the hospitalization during which the patient was enrolled. For patients who initially presented to the emergency department, time of hospital presentation was the time of emergency department arrival. For patients directly hospitalized without presenting to the emergency department, time of hospital presentation was the time of arrival at the admission unit. | Measure was analyzed in participants who had available data for date of hospital presentation. | Median | Inter-Quartile Range | hours |
| |||||||||||||
| COVID outcomes scale category at randomization | The COVID Outcomes Scale is a 7-category ordinal scale that classifies a patient's clinical status. Lower scores indicate more severely ill clinical status. Patients in the following categories at baseline were not eligible for enrollment: category 1 (death); category 6 (not hospitalized and unable to perform normal activities); and category 7 (not hospitalized and able to perform normal activities). | Count of Participants | Participants |
| |||||||||||||||
| Vasopressor use at enrollment | Count of Participants | Participants |
| ||||||||||||||||
| Total SOFA score at enrollment | The SOFA score categorizes illness severity based on organ dysfunction across 6 organ systems: respiratory, coagulation, liver, cardiovascular, central nervous system, and kidney. SOFA scores range from 0 to 24, with higher scores indicating greater illness severity. A SOFA score of 2 indicates moderate dysfunction in 1 organ system or mild dysfunction in 2 organ systems. | Median | Inter-Quartile Range | score |
| ||||||||||||||
| White blood cell count | Normal range for WBC: 3.9-10.7 | Measure is analyzed in participants with available data on white blood cell count. | Median | Inter-Quartile Range | cells ×10^3/μL |
| |||||||||||||
| Platelet count | Normal range for platelet: 135-371 Laboratory normal ranges were reported base on the clinical laboratory normal ranges from Vanderbilt University Medical Center. Normal ranges may vary across laboratories. | Measure is analyzed in participants with available data on platelet count. | Median | Inter-Quartile Range | cells ×10^3/μL |
| |||||||||||||
| Creatinine | Normal range for creatinine: 0.57-1.11 Laboratory normal ranges were reported base on the clinical laboratory normal ranges from Vanderbilt University Medical Center. Normal ranges may vary across laboratories. | Measure was analyzed in participants with available data on creatinine. | Median | Inter-Quartile Range | mg/dL |
| |||||||||||||
| Aspartate aminotransferase | Normal range for aspartate aminotransferase: 5-40 Laboratory normal ranges were reported base on the clinical laboratory normal ranges from Vanderbilt University Medical Center. Normal ranges may vary across laboratories. | Measure is analyzed in participants with available data on aspartate aminotransferase. | Median | Inter-Quartile Range | U/L |
| |||||||||||||
| Alanine aminotransferase | Normal range for alanine aminotransferase: 0-55 Laboratory normal ranges were reported base on the clinical laboratory normal ranges from Vanderbilt University Medical Center. Normal ranges may vary across laboratories. | Measure was analyzed in participants with available data on alanine aminotransferase. | Median | Inter-Quartile Range | U/L |
| |||||||||||||
| Bilateral infiltrates on chest imaging | Reported chest imaging interpretations were based on final interpretation from radiologists. | This measure was analyzed in participants with available data on bilateral infiltrates on chest imaging. | Count of Participants | Participants |
| ||||||||||||||
| QTc interval | Reported QTc was based on automated readings. | This measure was analyzed in participants with available data on QTc interval. | Median | Inter-Quartile Range | milliseconds |
|
| 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 | COVID Outcomes Scale Score on Study Day 15 (14 Days After Randomization) | We will determine the COVID Ordinal Scale for all patients on study day 15 COVID Ordinal Scale defined as:
| Posted | Median | Inter-Quartile Range | score on a scale | Assessed on study day 15 |
|
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | COVID Ordinal Outcomes Scale on Study Day 3 (2 Days After Randomization) | We will determine the COVID Ordinal Scale for all patients on study day 3 COVID Ordinal Scale defined as:
| Posted | Median | Inter-Quartile Range | score on a scale | assessed on study day 3 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | COVID Ordinal Outcomes Scale on Study Day 8 (7 Days After Randomization) | We will determine the COVID Ordinal Scale on study day 8 COVID Ordinal Scale defined as:
| Posted | Median | Inter-Quartile Range | score on a scale | assessed on study day 8 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | COVID Ordinal Outcomes Scale on Study Day 29 (28 Days After Randomization) | We will determine the COVID Ordinal Scale on study day 29 COVID Ordinal Scale defined as:
| Posted | Median | Inter-Quartile Range | score on a scale | assessed on study day 29 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | All-location, All-cause Mortality Assessed on Study Day 15 (14 Days After Randomization) | Vital status of the patient on day 15 will be determined using any of the following methods: medical record review, phone calls to patient or proxy. There were two patients for whom we were unable to collect their vital status. | Outcome was measured in participants with available data on vital status. One patient in the hydroxychloroquine group and one patient in the placebo group were lost to follow-up for vital status. | Posted | Count of Participants | Participants | assessed on study day 15 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | All-location, All-cause Mortality Assessed on Study Day 29 (28 Days After Randomization) | Vital status of the patient at day 28 will be determined using any of the following methods: medical record review, phone calls to patient or proxy. There were two patients for whom we were unable to collect their vital status. | Outcome was measured in participants with available data on vital status. One patient in the hydroxychloroquine group and one patient in the placebo group were lost to follow-up for vital status. | Posted | Count of Participants | Participants | assessed on study day 29 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Patients Dead or With Receipt of ECMO Between Enrollment and Day 28 | We will determine the number of patients who are either dead or on ECMO ( extracorporeal membrane oxygenation) between enrollment and day 28 | Outcome was measured in participants with available data on vital status or ECMO. One patient in the hydroxychloroquine group and one patient in the placebo group were lost to follow-up for vital status. | Posted | Count of Participants | Participants | Enrollment to Day 28 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Oxygen-free Days Through Day 28 | The number of calendar days between randomization and 28 days later that the patient is alive and without the use of oxygen therapy. Patients who die prior to day 28 are assigned zero oxygen free days. | Posted | Median | Inter-Quartile Range | days | 28 days after randomization |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Ventilator-free Days Through Day 28 | Ventilator-free days is defined to be 28 days minus the duration of mechanical ventilation through day 28. Participants who do not survive to day 28 are assigned zero ventilator-free days. | Posted | Median | Inter-Quartile Range | days | 28 days after randomization |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Vasopressor-free Days Through Day 28 | The number of calendar days between randomization and 28 days later that the patient is alive and without the use of vasopressor therapy. Patients who die prior to day 28 are assigned zero vasopressor free days. | Posted | Median | Inter-Quartile Range | days | 28 days after randomization |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | ICU-free Days to Day 28 | The number of days spent out of the ICU to day 28. Patients who die prior to day 28 are assigned zero ICU free days. | Posted | Median | Inter-Quartile Range | days | 28 days after randomization |
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| Secondary | Hospital-free Days to Day 28 | Defined as 28 days minus the number of days from randomization to discharge home.If a patient has not been discharged home prior to day 28 or dies prior to day 28, hospital free days will be zero. | Posted | Median | Inter-Quartile Range | days | 28 days after randomization |
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| Other Pre-specified | Number of Patients With Seizures to Day 28 | We will determine the number of patients that experience seizure between randomization and day 28 | Posted | Count of Participants | Participants | 28 days after randomization |
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| Other Pre-specified | Number of Patients With Atrial Arrhythmia to Day 28 | We will determine the number of patients that experience atrial arrhythmia between randomization and day 28 | Posted | Count of Participants | Participants | 28 days after randomization |
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| Other Pre-specified | Number of Patients With Ventricular Arrhythmia to Day 28 | We will determine the number of patients that experience ventricular arrhythmia between randomization and day 28 | Posted | Count of Participants | Participants | 28 days after randomization |
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| Other Pre-specified | Number of Patients With Cardiac Arrest to Day 28 | We will determine the number of patients that experience cardiac arrest between randomization and day 28 | Posted | Count of Participants | Participants | 28 days after randomization |
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| Other Pre-specified | Number of Patients With Elevation in Aspartate Aminotransferase or Alanine Aminotransferase to Twice the Local Upper Limit of Normal to Day 28 | We will determine the number of patients that experience elevation in aspartate aminotransferase or alanine aminotransferase to twice the local upper limit of normal between randomization and day 28 | Posted | Count of Participants | Participants | 28 days after randomization |
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| Other Pre-specified | Number of Patients With Acute Pancreatitis Arrest to Day 28 | We will determine the number of patients that experience acute pancreatitis between randomization and day 28 | Posted | Count of Participants | Participants | 28 days after randomization |
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| Other Pre-specified | Number of Patients With Acute Kidney Injury to day28 | We will determine the number of patients that experience acute kidney injury between randomization and day 28 | Posted | Count of Participants | Participants | 28 days after randomization |
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| Other Pre-specified | Number of Patients With Receipt of Renal Replacement Therapy to Day 28 | We will determine the number of patients that experience renal replacement therapy between randomization and day 28 | Posted | Count of Participants | Participants | 28 days after randomization |
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| Other Pre-specified | Number of Patients With Symptomatic Hypoglycemia to Day 28 | We will determine the number of patients that experience symptomatic hypoglycemia between randomization and day 28 | Posted | Count of Participants | Participants | 28 days after randomization |
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| Other Pre-specified | Number of Patients With Neutropenia to Day 28 | We will determine the number of patients that experience neutropenia between randomization and day 28 | Posted | Count of Participants | Participants | 28 days after randomization |
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| Other Pre-specified | Number of Patients With Lymphopenia to Day 28 | We will determine the number of patients that experience lymphopenia between randomization and day 28 | Posted | Count of Participants | Participants | 28 days after randomization |
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| Other Pre-specified | Number of Patients With Anemia to Day 28 | We will determine the number of patients that experience anemia between randomization and day 28 | Posted | Count of Participants | Participants | 28 days after randomization |
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| Other Pre-specified | Number of Patients With Thrombocytopenia to Day 28 | We will determine the number of patients that experience thrombocytopenia between randomization and day 28 | Posted | Count of Participants | Participants | 28 days after randomization |
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| Other Pre-specified | Number of Patients With Severe Dermatologic Reaction to Day 28 | We will determine the number of patients that experience severe dermatologic reaction between randomization and day 28 | Posted | Count of Participants | Participants | 28 days after randomization |
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| Other Pre-specified | Time to Recovery, Defined as Time to Reaching Level 5, 6, or 7 on the COVID Outcomes Scale, Which is the Time to the Earlier of Final Liberation From Supplemental Oxygen or Hospital Discharge | Time to recovery, defined as time to reaching level 5, 6, or 7 on the COVID Outcomes Scale, which is the time to the earlier of final liberation from supplemental oxygen or hospital discharge. Patients who die prior to day 28 are assigned 28 days for time to recovery. | Posted | Median | Inter-Quartile Range | days | 28 days after randomization |
|
Subjects were assessed for adverse events from enrollment through study day 29 or discharge, whichever occurs first. Investigators will determine if the event is serious or related to study drug.
Not provided
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 | Hydroxychlorquine | Participants assigned to the hydroxychloroquine arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. Hydroxychloroquine: Hydroxychloroquine is available in 200 mg oral tablets of hydroxychloroquine sulfate. For this COVID-19 trial, we will use an oral or enteral dose of hydroxychloroquine 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. | 25 | 242 | 14 | 242 | 30 | 242 |
| EG001 | Placebo | Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. Placebo: Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. | 25 | 237 | 11 | 237 | 21 | 237 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiac Arrest | Cardiac disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Myocardial Infarction | Cardiac disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Ventricular Tachycardia | Cardiac disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Abdominal Distension | Gastrointestinal disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Bleeding Gastrointestinal | Gastrointestinal disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Gall stones | Gastrointestinal disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Nausea, Vomiting, Hematemesis | Gastrointestinal disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Obstruction Bowel | Gastrointestinal disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Death | General disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Hypokalemia | Investigations | MedDRA (10.0) | Non-systematic Assessment |
| |
| Reaction Nonspecific | Investigations | MedDRA (10.0) | Non-systematic Assessment |
| |
| Hematoma Muscle | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Joint Pain | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Edema Cerebral | Nervous system disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Encephalopathy | Nervous system disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Intracranial hemorrhage | Nervous system disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Stroke | Nervous system disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Respiratory Distress | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Shortness of Breath | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Hemorrhage Retroperitoneal | Vascular disorders | MedDRA (10.0) | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leukocytosis | Blood and lymphatic system disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Atrial Arrythmia | Cardiac disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Bradycardia | Cardiac disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Cardiac Arrhythmia | Cardiac disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Cardiomyopathy | Cardiac disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Chest Pain | Cardiac disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Conduction Disorder | Cardiac disorders | MedDRA (10.0) | Non-systematic Assessment |
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| EKG Abnormality: Non-Specific | Cardiac disorders | MedDRA (10.0) | Non-systematic Assessment |
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| Premature Ventricular Contractions | Cardiac disorders | MedDRA (10.0) | Non-systematic Assessment |
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| Prolonged QTc | Cardiac disorders | MedDRA (10.0) | Non-systematic Assessment |
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| Sinus Bradycardia | Cardiac disorders | MedDRA (10.0) | Non-systematic Assessment |
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| Hypoglycemia | Endocrine disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Nausea, Vomiting | Gastrointestinal disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Nausea, Diarrhea | Gastrointestinal disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Contrast Extravasation | General disorders | MedDRA (10.0) | Non-systematic Assessment |
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| Allergic Reaction | Immune system disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| ALT Increased | Investigations | MedDRA (10.0) | Non-systematic Assessment |
| |
| AST Increased | Investigations | MedDRA (10.0) | Non-systematic Assessment |
| |
| Multiple Liver Function Tests Abnormal | Investigations | MedDRA (10.0) | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Neuropathy Peripheral | Nervous system disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Kidney Function Abnormal | Renal and urinary disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Itching | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Flushing | Vascular disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Vagal Reaction | Vascular disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Nosebleed | Vascular disorders | MedDRA (10.0) | Non-systematic Assessment |
|
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| B.Taylor Thompson, MD | Mass General Hopsital (PETAL Network Coordinating Center) | 617-726-8854 | TTHOMPSON1@mgh.harvard.edu |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 17, 2020 | Dec 1, 2020 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D018352 | Coronavirus Infections |
| D045169 | Severe Acute Respiratory Syndrome |
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
| D012141 | Respiratory Tract Infections |
| D012140 | Respiratory Tract Diseases |
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D008171 | Lung Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D006886 | Hydroxychloroquine |
| ID | Term |
|---|---|
| D002738 | Chloroquine |
| D000634 | Aminoquinolines |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
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