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

NCT04332991 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: PETAL 05 Orchid
• Study Type: interventional
• Target: 479
• Locations: 1 country
• Sites: 40

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.

Conditions

Coronavirus; Acute Respiratory Infection; SARS-CoV Infection

Keywords

COVID-19

Outcome Measures

Primary Outcomes (1)

• 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: 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)

  Assessed on study day 15

Secondary Outcomes (11)

• COVID Ordinal Outcomes Scale on Study Day 3 (2 Days After Randomization)

  assessed on study day 3

• COVID Ordinal Outcomes Scale on Study Day 8 (7 Days After Randomization)

  assessed on study day 8

• COVID Ordinal Outcomes Scale on Study Day 29 (28 Days After Randomization)

  assessed on study day 29

• All-location, All-cause Mortality Assessed on Study Day 15 (14 Days After Randomization)

  assessed on study day 15

• All-location, All-cause Mortality Assessed on Study Day 29 (28 Days After Randomization)

  assessed on study day 29

Other Outcomes (15)

• Number of Patients With Seizures to Day 28

  28 days after randomization

• Number of Patients With Atrial Arrhythmia to Day 28

  28 days after randomization

• Number of Patients With Ventricular Arrhythmia to Day 28

  28 days after randomization

Study Arms (2)

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.

Drug: Hydroxychloroquine

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.

Drug: Placebo

Interventions

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.

Hydroxychlorquine

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.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• cough
• fever (\> 37.5° C / 99.5° F)
• 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).
• sore throat
• Laboratory-confirmed SARS-CoV-2 infection within the past 10 days prior to randomization.

You may not qualify if:

• Prisoner
• Pregnancy
• Breast feeding
• Symptoms of acute respiratory infection for \>10 days before 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (40)

University of Arizona

Tucson, Arizona, 85721, United States

Location

UCSF Fresno

Fresno, California, 93701, United States

Location

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

UCSF Medical Center

San Francisco, California, 94143, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Medical Center of Aurora

Aurora, Colorado, 80045, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Denver Health Medical Center

Denver, Colorado, 80204, United States

Location

St. Joseph Hospital

Denver, Colorado, 80218, United States

Location

University of Florida

Gainesville, Florida, 32608, United States

Location

University of Kentucky

Lexington, Kentucky, 40506, United States

Location

University Medical Center

New Orleans, Louisiana, 70112, United States

Location

Maine Medical Center

Portland, Maine, 04102, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02445, United States

Location

Baystate Medical Center

Springfield, Massachusetts, 01199, United States

Location

St. Vincent's Hospital

Worcester, Massachusetts, 01608, United States

Location

University of Michigan Medical Center

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Medical Center

Detroit, Michigan, 48025, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Montefiore Medical Center-Weiler

The Bronx, New York, 10461, United States

Location

Montefiore Medical Center-Moses

The Bronx, New York, 10467, United States

Location

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Penn State Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

UPMC Presbyterian/Mercy/Shadyside

Pittsburgh, Pennsylvania, 15261, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37221, United States

Location

University of Texas Health Science Center

Houston, Texas, 77030, United States

Location

Intermountain Medical Center

Murray, Utah, 84107, United States

Location

University of Utah Hospital

Salt Lake City, Utah, 84132, United States

Location

VCU Medical Center

Richmond, Virginia, 23298, United States

Location

Harborview Medical Center

Seattle, Washington, 98104, United States

Location

Swedish Hospital First Hill

Seattle, Washington, 98122, United States

Location

Related Publications (2)

• 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.

  PMID: 33165621 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.

  PMID: 32492354 DERIVED

Related Links

• Website for the PETAL Network

MeSH Terms

Conditions

Coronavirus Infections; Severe Acute Respiratory Syndrome; COVID-19

Interventions

Hydroxychloroquine

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: B.Taylor Thompson, MD
• Organization: Mass General Hopsital (PETAL Network Coordinating Center)

TTHOMPSON1@mgh.harvard.edu

617-726-8854

Study Officials

• Boyd Taylor Thompson, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Patients, treating clinicians, trial personnel, and outcome assessors will be blinded to group assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Co-Prinicipal Investigator PETAL CCC

Model Details: 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.

Study Record Dates

• First Submitted: March 31, 2020
• First Posted: April 3, 2020
• Study Start: April 2, 2020
• Primary Completion: June 19, 2020
• Study Completion: July 23, 2020
• Last Updated: March 17, 2021
• Results First Posted: March 17, 2021

Record last verified: 2021-03

Locations

US (40)