Outcomes Related to COVID-19 Treated With Hydroxychloroquine Among In-patients With Symptomatic Disease

Phase 3

Completed

Conditions: SARS-CoV Infection
Coronavirus
Acute Respiratory Infection

Interventions: Drug: Placebo
Drug: Hydroxychloroquine

Registration Number: NCT04332991

Lead Sponsor: Massachusetts General Hospital

Brief Summary: 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.

Detailed Description: 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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Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 479

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:
1. cough
2. fever (> 37.5° C / 99.5° F)
3. shortness of breath (operationalized as any of the following: subjective shortness of breath reported by patient or surrogate; tachypnea with respiratory rate ≥22 /minute; hypoxemia, defined as SpO2 <92% on room air, new receipt of supplemental oxygen to maintain SpO2 ≥92%, or increased supplemental oxygen to maintain SpO2 ≥92% for a patient on chronic oxygen therapy).
4. sore throat
Laboratory-confirmed SARS-CoV-2 infection within the past 10 days prior to randomization.

Exclusion Criteria

Prisoner
Pregnancy
Breast feeding
Symptoms of acute respiratory infection for >10 days before randomization
>48 hours between meeting inclusion criteria and randomization
Seizure disorder
Porphyria cutanea tarda
Diagnosis of Long QT syndrome
QTc >500 ms on electrocardiogram within 72 hours prior to enrollment
Known allergy to hydroxychloroquine, chloroquine, or amodiaquine
Receipt in the 12 hours prior to enrollment, or planned administration during the 5-day study period that treating clinicians feel cannot be substituted for another medication, of any of the following: amiodarone; cimetidine; dofetilide; phenobarbital; phenytoin; sotalol
Receipt of >1 dose of hydroxychloroquine or chloroquine in the 10 days prior to enrollment
Inability to receive enteral medications
Refusal or inability to be contacted on Day 15 for clinical outcome assessment if discharged prior to day 15
Previous enrollment in this trial
The treating clinical team does not believe equipoise exists regarding the use of hydroxychloroquine for the treatment of this patient

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	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.
Hydroxychlorquine	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.

Primary Outcome Measures

Name	Time	Method
COVID Outcomes Scale Score on Study Day 15 (14 Days After Randomization)	Assessed on study day 15	We will determine the COVID Ordinal Scale for all patients on study day 15 COVID Ordinal Scale defined as: 1. Death 2. Hospitalized on invasive mechanical ventilation or ECMO ( extracorporeal membrane oxygenation) 3. Hospitalized on non-invasive ventilation or high flow nasal cannula 4. Hospitalized on supplemental oxygen 5. Hospitalized not on supplemental oxygen 6. Not hospitalized with limitation in activity (continued symptoms) 7. Not hospitalized without limitation in activity (no symptoms)

Secondary Outcome Measures

Name	Time	Method
COVID Ordinal Outcomes Scale on Study Day 29 (28 Days After Randomization)	assessed on study day 29	We will determine the COVID Ordinal Scale on study day 29 COVID Ordinal Scale defined as: 1. Death 2. Hospitalized on invasive mechanical ventilation or ECMO ( extracorporeal membrane oxygenation) 3. Hospitalized on non-invasive ventilation or high flow nasal cannula 4. Hospitalized on supplemental oxygen 5. Hospitalized not on supplemental oxygen 6. Not hospitalized with limitation in activity (continued symptoms) 7. Not hospitalized without limitation in activity (no symptoms)
All-location, All-cause Mortality Assessed on Study Day 15 (14 Days After Randomization)	assessed on study day 15	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.
Oxygen-free Days Through Day 28	28 days after randomization	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.
COVID Ordinal Outcomes Scale on Study Day 3 (2 Days After Randomization)	assessed on study day 3	We will determine the COVID Ordinal Scale for all patients on study day 3 COVID Ordinal Scale defined as: 1. Death 2. Hospitalized on invasive mechanical ventilation or ECMO ( extracorporeal membrane oxygenation) 3. Hospitalized on non-invasive ventilation or high flow nasal cannula 4. Hospitalized on supplemental oxygen 5. Hospitalized not on supplemental oxygen 6. Not hospitalized with limitation in activity (continued symptoms) 7. Not hospitalized without limitation in activity (no symptoms)
COVID Ordinal Outcomes Scale on Study Day 8 (7 Days After Randomization)	assessed on study day 8	We will determine the COVID Ordinal Scale on study day 8 COVID Ordinal Scale defined as: 1. Death 2. Hospitalized on invasive mechanical ventilation or ECMO ( extracorporeal membrane oxygenation) 3. Hospitalized on non-invasive ventilation or high flow nasal cannula 4. Hospitalized on supplemental oxygen 5. Hospitalized not on supplemental oxygen 6. Not hospitalized with limitation in activity (continued symptoms) 7. Not hospitalized without limitation in activity (no symptoms)
All-location, All-cause Mortality Assessed on Study Day 29 (28 Days After Randomization)	assessed on study day 29	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.
Number of Patients Dead or With Receipt of ECMO Between Enrollment and Day 28	Enrollment to Day 28	We will determine the number of patients who are either dead or on ECMO ( extracorporeal membrane oxygenation) between enrollment and day 28
Ventilator-free Days Through Day 28	28 days after randomization	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.
Vasopressor-free Days Through Day 28	28 days after randomization	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.
ICU-free Days to Day 28	28 days after randomization	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.
Hospital-free Days to Day 28	28 days after randomization	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.

Trial Locations

Locations (40): Harborview Medical Center
🇺🇸
Seattle, Washington, United States
University of Cincinnati Medical Center
🇺🇸
Cincinnati, Ohio, United States
Maine Medical Center
🇺🇸
Portland, Maine, United States
Medical University of South Carolina
🇺🇸
Charleston, South Carolina, United States
University of Colorado Hospital
🇺🇸
Aurora, Colorado, United States
Denver Health Medical Center
🇺🇸
Denver, Colorado, United States
University of Utah Hospital
🇺🇸
Salt Lake City, Utah, United States
University of Arizona
🇺🇸
Tucson, Arizona, United States
Wake Forest Baptist Medical Center
🇺🇸
Winston-Salem, North Carolina, United States
University Medical Center
🇺🇸
New Orleans, Louisiana, United States
UCSF Medical Center
🇺🇸
San Francisco, California, United States
St. Joseph Hospital
🇺🇸
Denver, Colorado, United States
Temple University Hospital
🇺🇸
Philadelphia, Pennsylvania, United States
University of Florida
🇺🇸
Gainesville, Florida, United States
UC Davis Medical Center
🇺🇸
Sacramento, California, United States
Henry Ford Medical Center
🇺🇸
Detroit, Michigan, United States
Medical Center of Aurora
🇺🇸
Aurora, Colorado, United States
Stanford University
🇺🇸
Stanford, California, United States
Montefiore Medical Center-Moses
🇺🇸
Bronx, New York, United States
Cleveland Clinic Foundation
🇺🇸
Cleveland, Ohio, United States
University of Texas Health Science Center
🇺🇸
Houston, Texas, United States
Ohio State University Wexner Medical Center
🇺🇸
Columbus, Ohio, United States
Baystate Medical Center
🇺🇸
Springfield, Massachusetts, United States
UPMC Presbyterian/Mercy/Shadyside
🇺🇸
Pittsburgh, Pennsylvania, United States
Swedish Hospital First Hill
🇺🇸
Seattle, Washington, United States
UCSF Fresno
🇺🇸
Fresno, California, United States
Ronald Reagan UCLA Medical Center
🇺🇸
Los Angeles, California, United States
Montefiore Medical Center-Weiler
🇺🇸
Bronx, New York, United States
Intermountain Medical Center
🇺🇸
Murray, Utah, United States
VCU Medical Center
🇺🇸
Richmond, Virginia, United States
Beth Israel Deaconess Medical Center
🇺🇸
Boston, Massachusetts, United States
University of Kentucky
🇺🇸
Lexington, Kentucky, United States
St. Vincent's Hospital
🇺🇸
Worcester, Massachusetts, United States
University of Mississippi Medical Center
🇺🇸
Jackson, Mississippi, United States
University of Michigan Medical Center
🇺🇸
Ann Arbor, Michigan, United States
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Vanderbilt University Medical Center
🇺🇸
Nashville, Tennessee, United States
Brigham and Women's Hospital
🇺🇸
Boston, Massachusetts, United States
Oregon Health and Science University
🇺🇸
Portland, Oregon, United States
Penn State Hershey Medical Center
🇺🇸
Hershey, Pennsylvania, United States