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

Coronavirus Clinical Trial

— ORCHID  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04332991
• Other study ID #: PETAL 05 Orchid
• Status: Completed
• Phase: Phase 3
• Start date: April 2, 2020
• Est. completion date: July 23, 2020

Study information

• Verified date: March 2021
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 479
• Est. completion date: July 23, 2020
• Est. primary completion date: June 19, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Respiratory Infection
• Communicable Diseases
• Coronavirus
• Coronavirus Infections
• Infection
• Respiratory Tract Infections
• SARS-CoV Infection
• Severe Acute Respiratory Syndrome

Intervention

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.
• 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.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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	28 days after randomization
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
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: Death; Hospitalized on invasive mechanical ventilation or ECMO ( extracorporeal membrane oxygenation); Hospitalized on non-invasive ventilation or high flow nasal cannula; Hospitalized on supplemental oxygen; Hospitalized not on supplemental oxygen; Not hospitalized with limitation in activity (continued symptoms); Not hospitalized without limitation in activity (no symptoms)	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: Death; Hospitalized on invasive mechanical ventilation or ECMO ( extracorporeal membrane oxygenation); Hospitalized on non-invasive ventilation or high flow nasal cannula; Hospitalized on supplemental oxygen; Hospitalized not on supplemental oxygen; Not hospitalized with limitation in activity (continued symptoms); Not hospitalized without limitation in activity (no symptoms)	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: Death; Hospitalized on invasive mechanical ventilation or ECMO ( extracorporeal membrane oxygenation); Hospitalized on non-invasive ventilation or high flow nasal cannula; Hospitalized on supplemental oxygen; Hospitalized not on supplemental oxygen; Not hospitalized with limitation in activity (continued symptoms); Not hospitalized without limitation in activity (no symptoms)	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: Death; Hospitalized on invasive mechanical ventilation or ECMO ( extracorporeal membrane oxygenation); Hospitalized on non-invasive ventilation or high flow nasal cannula; Hospitalized on supplemental oxygen; Hospitalized not on supplemental oxygen; Not hospitalized with limitation in activity (continued symptoms); Not hospitalized without limitation in activity (no symptoms)	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.	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.	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	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.	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.	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.	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.	28 days after randomization
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.	28 days after randomization

External Links

•   Website for the PETAL Network