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

NCT ID: NCT04332991

Last Updated: 2021-03-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 479 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-04-02
• Study Completion Date: 2020-07-23

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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Conditions

Coronavirus; Acute Respiratory Infection; SARS-CoV Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Hydroxychloroquine

Intervention Type: 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.

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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.

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

Exclusion Criteria

1. Prisoner

2. Pregnancy

3. Breast feeding

4. Symptoms of acute respiratory infection for >10 days before randomization

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Boyd Taylor Thompson

Co-Prinicipal Investigator PETAL CCC

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Boyd Taylor Thompson, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

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

The Bronx, New York, United States

Montefiore Medical Center-Moses

The 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

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 33165621 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32492354 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://petalnet.org

Website for the PETAL Network

Other Identifiers

PETAL 05 Orchid

Identifier Type: -

Identifier Source: org_study_id