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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Drug: 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.
Drug: 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.
Inclusion Criteria:
1. Age ≥18 years
2. Currently hospitalized or in an emergency department with anticipated hospitalization.
3. 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
4. Laboratory-confirmed SARS-CoV-2 infection within the past 10 days prior to
randomization.
Exclusion Criteria:
1. Prisoner
2. Pregnancy
3. Breast feeding
4. Symptoms of acute respiratory infection for >10 days before randomization
5. >48 hours between meeting inclusion criteria and randomization
6. Seizure disorder
7. Porphyria cutanea tarda
8. Diagnosis of Long QT syndrome
9. QTc >500 ms on electrocardiogram within 72 hours prior to enrollment
10. Known allergy to hydroxychloroquine, chloroquine, or amodiaquine
11. 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
12. Receipt of >1 dose of hydroxychloroquine or chloroquine in the 10 days prior to
enrollment
13. Inability to receive enteral medications
14. Refusal or inability to be contacted on Day 15 for clinical outcome assessment if
discharged prior to day 15
15. Previous enrollment in this trial
16. The treating clinical team does not believe equipoise exists regarding the use of
hydroxychloroquine for the treatment of this patient
University of Arizona
Tucson, Arizona, United States
UCSF Fresno
Fresno, California, United States
Ronald Reagan UCLA Medical Center
Los Angeles, California, United States
UC Davis Medical Center
Sacramento, California, United States
UCSF Medical Center
San Francisco, California, United States
Stanford University
Stanford, California, United States
Medical Center of Aurora
Aurora, Colorado, United States
University of Colorado Hospital
Aurora, Colorado, United States
Denver Health Medical Center
Denver, Colorado, United States
St. Joseph Hospital
Denver, Colorado, United States
University of Florida
Gainesville, Florida, United States
University of Kentucky
Lexington, Kentucky, United States
University Medical Center
New Orleans, Louisiana, United States
Maine Medical Center
Portland, Maine, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Brigham and Women's Hospital
Boston, Massachusetts, United States
Baystate Medical Center
Springfield, Massachusetts, United States
St. Vincent's Hospital
Worcester, Massachusetts, United States
University of Michigan Medical Center
Ann Arbor, Michigan, United States
Henry Ford Medical Center
Detroit, Michigan, United States
University of Mississippi Medical Center
Jackson, Mississippi, United States
Montefiore Medical Center-Weiler
Bronx, New York, United States
Montefiore Medical Center-Moses
Bronx, New York, United States
Wake Forest Baptist Medical Center
Winston-Salem, North Carolina, United States
University of Cincinnati Medical Center
Cincinnati, Ohio, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States
Ohio State University Wexner Medical Center
Columbus, Ohio, United States
Oregon Health and Science University
Portland, Oregon, United States
Penn State Hershey Medical Center
Hershey, Pennsylvania, United States
Temple University Hospital
Philadelphia, Pennsylvania, United States
UPMC Presbyterian/Mercy/Shadyside
Pittsburgh, Pennsylvania, United States
Medical University of South Carolina
Charleston, South Carolina, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
University of Texas Health Science Center
Houston, Texas, United States
Intermountain Medical Center
Murray, Utah, United States
University of Utah Hospital
Salt Lake City, Utah, United States
VCU Medical Center
Richmond, Virginia, United States
Harborview Medical Center
Seattle, Washington, United States
Swedish Hospital First Hill
Seattle, Washington, United States
Boyd Taylor Thompson, MD, Principal Investigator
Massachusetts General Hospital