Clinical trial NCT04332991: Outcomes Related to COVID-19 Treated With Hydroxychloroquine Among In-patients With Symptomatic Disease
Official title: Outcomes Related to COVID-19 Treated With Hydroxychloroquine Among In-patients With Symptomatic Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Coronavirus
Acute Respiratory Infection
SARS-CoV Infection
Keywords: COVID-19
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2020-04-03
Enrollment: 479
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.

.

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.

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

Primary outcomes:
measure: COVID Outcomes Scale Score on Study Day 15 (14 Days After Randomization)
timeFrame: Assessed on study day 15
Secondary outcomes:
measure: COVID Ordinal Outcomes Scale on Study Day 3 (2 Days After Randomization)
timeFrame: assessed on study day 3
measure: COVID Ordinal Outcomes Scale on Study Day 8 (7 Days After Randomization)
timeFrame: assessed on study day 8
measure: COVID Ordinal Outcomes Scale on Study Day 29 (28 Days After Randomization)
timeFrame: assessed on study day 29
measure: All-location, All-cause Mortality Assessed on Study Day 15 (14 Days After Randomization)
timeFrame: assessed on study day 15
measure: All-location, All-cause Mortality Assessed on Study Day 29 (28 Days After Randomization)
timeFrame: assessed on study day 29
measure: Number of Patients Dead or With Receipt of ECMO Between Enrollment and Day 28
timeFrame: Enrollment to Day 28
measure: Oxygen-free Days Through Day 28
timeFrame: 28 days after randomization
measure: Ventilator-free Days Through Day 28
timeFrame: 28 days after randomization
measure: Vasopressor-free Days Through Day 28
timeFrame: 28 days after randomization
measure: ICU-free Days to Day 28
timeFrame: 28 days after randomization
measure: Hospital-free Days to Day 28
timeFrame: 28 days after randomization
Other outcomes:
measure: Number of Patients With Seizures to Day 28
timeFrame: 28 days after randomization
measure: Number of Patients With Atrial Arrhythmia to Day 28
timeFrame: 28 days after randomization
measure: Number of Patients With Ventricular Arrhythmia to Day 28
timeFrame: 28 days after randomization
measure: Number of Patients With Cardiac Arrest to Day 28
timeFrame: 28 days after randomization
measure: Number of Patients With Elevation in Aspartate Aminotransferase or Alanine Aminotransferase to Twice the Local Upper Limit of Normal to Day 28
timeFrame: 28 days after randomization
measure: Number of Patients With Acute Pancreatitis Arrest to Day 28
timeFrame: 28 days after randomization
measure: Number of Patients With Acute Kidney Injury to day28
timeFrame: 28 days after randomization
measure: Number of Patients With Receipt of Renal Replacement Therapy to Day 28
timeFrame: 28 days after randomization
measure: Number of Patients With Symptomatic Hypoglycemia to Day 28
timeFrame: 28 days after randomization
measure: Number of Patients With Neutropenia to Day 28
timeFrame: 28 days after randomization
measure: Number of Patients With Lymphopenia to Day 28
timeFrame: 28 days after randomization
measure: Number of Patients With Anemia to Day 28
timeFrame: 28 days after randomization
measure: Number of Patients With Thrombocytopenia to Day 28
timeFrame: 28 days after randomization
measure: Number of Patients With Severe Dermatologic Reaction to Day 28
timeFrame: 28 days after randomization
measure: 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
timeFrame: 28 days after randomization
Locations:
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Fresno
country: United States
facility: UCSF Fresno
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: Medical Center of Aurora
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Denver
country: United States
facility: Denver Health Medical Center
state: Colorado
city: Denver
country: United States
facility: St. Joseph Hospital
state: Colorado
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: New Orleans
country: United States
facility: University Medical Center
state: Louisiana
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: Worcester
country: United States
facility: St. Vincent's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Medical Center
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Bronx
country: United States
facility: Montefiore Medical Center-Weiler
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center-Moses
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Wexner Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Presbyterian/Mercy/Shadyside
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: University of Texas Health Science Center
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Hospital
state: Utah
city: Richmond
country: United States
facility: VCU Medical Center
state: Virginia
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Seattle
country: United States
facility: Swedish Hospital First Hill
state: Washington
Study officials:
affiliation: Massachusetts General Hospital
name: Boyd Taylor Thompson, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.