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CoronavirusPhase 3ORCHIDNCT04332991

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

A Phase 3 study testing Hydroxychloroquine in people with Coronavirus and Acute Respiratory Infection, run by Massachusetts General Hospital at 40 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Hydroxychloroquine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
479 participants
Where
40 sitesUnited States
Study dates
2 Apr 2020to 23 Jul 2020
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • Prisoner
  • Pregnancy
  • Breast feeding
  • Symptoms of acute respiratory infection for >10 days before randomization
  • >48 hours between meeting inclusion criteria and randomization
  • Seizure disorder
Show all 16Show fewer
  • 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

Trial locations and contacts

40 sites in 1 country.

40 sites in 1 country

United States40 sites

  • University of Michigan Medical Center

    Ann Arbor, Michigan, 48109

  • Medical Center of Aurora

    Aurora, Colorado, 80045

  • University of Colorado Hospital

    Aurora, Colorado, 80045

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02115

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02445

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • University of Cincinnati Medical Center

    Cincinnati, Ohio, 45219

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Ohio State University Wexner Medical Center

    Columbus, Ohio, 43210

  • Denver Health Medical Center

    Denver, Colorado, 80204

  • St. Joseph Hospital

    Denver, Colorado, 80218

  • Henry Ford Medical Center

    Detroit, Michigan, 48025

  • UCSF Fresno

    Fresno, California, 93701

  • University of Florida

    Gainesville, Florida, 32608

  • Penn State Hershey Medical Center

    Hershey, Pennsylvania, 17033

  • University of Texas Health Science Center

    Houston, Texas, 77030

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • University of Kentucky

    Lexington, Kentucky, 40506

  • Ronald Reagan UCLA Medical Center

    Los Angeles, California, 90095

  • Intermountain Medical Center

    Murray, Utah, 84107

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37221

  • University Medical Center

    New Orleans, Louisiana, 70112

  • Temple University Hospital

    Philadelphia, Pennsylvania, 19140

  • UPMC Presbyterian/Mercy/Shadyside

    Pittsburgh, Pennsylvania, 15261

  • Maine Medical Center

    Portland, Maine, 04102

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • VCU Medical Center

    Richmond, Virginia, 23298

  • UC Davis Medical Center

    Sacramento, California, 95817

  • University of Utah Hospital

    Salt Lake City, Utah, 84132

  • UCSF Medical Center

    San Francisco, California, 94143

  • Harborview Medical Center

    Seattle, Washington, 98104

  • Swedish Hospital First Hill

    Seattle, Washington, 98122

  • Baystate Medical Center

    Springfield, Massachusetts, 01199

  • Stanford University

    Stanford, California, 94305

  • Montefiore Medical Center-Weiler

    The Bronx, New York, 10461

  • Montefiore Medical Center-Moses

    The Bronx, New York, 10467

  • University of Arizona

    Tucson, Arizona, 85721

  • Wake Forest Baptist Medical Center

    Winston-Salem, North Carolina, 27157

  • St. Vincent's Hospital

    Worcester, Massachusetts, 01608

Other trials in United States

About this study

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.

Read the 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.

.

Being tested
Hydroxychloroquine, Placebo
Keywords
COVID-19
Medical subject headings
Coronavirus Infections, Severe Acute Respiratory Syndrome, COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HydroxychloroquineDrug

    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.

  • PlaceboDrug

    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.

Study groups in NCT04332991
Study groupRoleWhat they receive
HydroxychlorquineActive comparatorParticipants 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.
Receives: Drug: Hydroxychloroquine
PlaceboPlacebo comparatorParticipants 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.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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)

    Measured: Assessed on study day 15

Secondary outcomes (11)

  1. 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:

    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)

    Measured: assessed on study day 3

  2. 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:

    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)

    Measured: assessed on study day 8

  3. 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:

    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)

    Measured: assessed on study day 29

  4. 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.

    Measured: assessed on study day 15

  5. 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.

    Measured: assessed on study day 29

  6. 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

    Measured: Enrollment to Day 28

  7. 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.

    Measured: 28 days after randomization

  8. 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.

    Measured: 28 days after randomization

  9. 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.

    Measured: 28 days after randomization

  10. 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.

    Measured: 28 days after randomization

  11. 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.

    Measured: 28 days after randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Apr 2020
  2. Study start2 Apr 2020
  3. Primary completion19 Jun 2020
  4. Study completion23 Jul 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
479 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04332991
Sponsor's protocol ID
PETAL 05 Orchid
Acronym
ORCHID
Status last verified
Mar 2021
First submitted
31 Mar 2020
Last updated
17 Mar 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 33165621

  • 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.

    PubMed 32492354

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Hydroxychloroquine in people with Coronavirus and Acute Respiratory Infection, run by Massachusetts General Hospital at 40 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 40 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

COVID Outcomes Scale Score on Study Day 15 (14 Days After Randomization) (time frame: Assessed on study day 15). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04332991, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2021.

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