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Trial of Early Therapies During Non-hospitalized Outpatient Window for COVID-19 (TREAT NOW)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04372628
Recruitment Status : Not yet recruiting
First Posted : May 4, 2020
Last Update Posted : May 19, 2020
Sponsor:
Collaborator:
AbbVie
Information provided by (Responsible Party):
Todd Rice, Vanderbilt University Medical Center

Brief Summary:
Blinded, multicenter, placebo-controlled, randomized clinical trial evaluating hydroxychloroquine vs lopinavir/ritonavir vs placebo in early outpatient treatment of adults with COVID-19

Condition or disease Intervention/treatment Phase
COVID-19 Drug: Hydroxychloroquine Drug: Lopinavir/ritonavir 400 mg/100 mg Other: Placebo Phase 2

Detailed Description:
We will conduct an investigator-initiated, multicenter, blinded, placebo-controlled, randomized clinical trial evaluating hydroxychloroquine vs. lopinavir/ritonavir vs placebo for early treatment of adults with COVID-19 in the outpatient setting prior to hospitalization. Patients, treating clinicians, and study personnel will all be blinded to study group assignment.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 900 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Blinded, multicenter, placebo-controlled randomized clinical trial
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Hydroxychloroquine tablets, matching placebo, tablets, or lopinavir/ritonavir tablets
Primary Purpose: Treatment
Official Title: Trial of Early Therapies During Non-hospitalized Outpatient Window (TREAT NOW) for COVID-18
Estimated Study Start Date : May 31, 2020
Estimated Primary Completion Date : December 1, 2020
Estimated Study Completion Date : May 1, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Group 1 - Hydroxychloroquine then Placebo
Hydroxychloroquine 400 mg orally twice daily for two doses (Day 1), then 200 mg twice daily for subsequent eight doses (Day 2-5), then placebo twice daily for subsequent eighteen doses (Days 6-14)
Drug: Hydroxychloroquine
Hydroxychloroquine 200 mg tablets
Other Name: Plaquenil

Other: Placebo
matched placebo

Active Comparator: Group 2 - Lopinavir/ritonavir
Lopinavir/ritonavir 400 mg/100 mg orally twice daily for twenty-eight doses (Days 1-14)
Drug: Lopinavir/ritonavir 400 mg/100 mg
lopinavir/ritonavir tablets
Other Name: Kaletra

Placebo Comparator: Control Group
Placebo matched to hydroxychloroquine orally twice daily for 14 days
Other: Placebo
matched placebo




Primary Outcome Measures :
  1. Modified COVID Ordinal Outcomes Scale: Study Day 15 [ Time Frame: Day 15 ]
    1. Death
    2. Hospitalized on mechanical ventilation or extracorporeal membrane oxygenator (ECMO)
    3. Hospitalized on supplemental oxygen
    4. Hospitalized not on supplemental oxygen
    5. Not hospitalized with symptoms and limitation in activity
    6. Not hospitalized with symptoms but with no limitation in activity
    7. Not hospitalized without symptoms nor limitation in activity symptoms at the milder end of the scale for this outpatient trial


Secondary Outcome Measures :
  1. Modified COVID Ordinal Outcome Scale: Study Day 8 [ Time Frame: Day 8 ]
    1. Death
    2. Hospitalized on mechanical ventilation or ECMO
    3. Hospitalized on supplemental oxygen
    4. Hospitalized not on supplemental oxygen
    5. Not hospitalized with symptoms and limitation in activity
    6. Not hospitalized with symptoms but with no limitation in activity
    7. Not hospitalized without symptoms nor limitation in activity

  2. Modified COVID Ordinal Outcome Scale: Study Day 29 [ Time Frame: Day 29 ]
    1. Death
    2. Hospitalized on mechanical ventilation or ECMO
    3. Hospitalized on supplemental oxygen
    4. Hospitalized not on supplemental oxygen
    5. Not hospitalized with symptoms and limitation in activity
    6. Not hospitalized with symptoms but with no limitation in activity
    7. Not hospitalized without symptoms nor limitation in activity Ordinal Scale

  3. Proportion of patients hospitalized: Day 1 to 29 [ Time Frame: Day 1 to Day 29 ]
    Proportion hospitalized

  4. Time to hospitalization Day 1 to Day 29 [ Time Frame: Day 1 to Day 29 ]
    Number of days from enrollment to hospitalization

  5. Time to symptom resolution: Day 1 to Day 29 [ Time Frame: Day 1 to Day 29 ]
    Number of days from enrollment to resolution of COVID-19 symptoms

  6. All-cause, all-location mortality: Day 1 to Day 29 [ Time Frame: Day 1 to Day 29 ]
    Survival status

  7. Oxygen-free days: Day 1 to Day 29 [ Time Frame: Day 1 to Day 29 ]
    Number of Days without oxygen

  8. Fever-free days: Day 1 to Day 29 [ Time Frame: Day 1 to Day 29 ]
    Number of days without fever

  9. Ventilator-free days: Day 1 to Day 29 [ Time Frame: Day 1 to Day 29 ]
    Number of days without ventilator use

  10. ICU-free days: Day 1 to Day 29 [ Time Frame: Day 1 to Day 29 ]
    Number of days outside the ICU

  11. Hospital-free days: Day 1 to Day 29 [ Time Frame: Day 1 to Day 29 ]
    Number of days outside the hospital



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥18 years
  2. Laboratory-confirmed severe acute respiratory syndrome- coronavirus-2 (SARS-CoV-2) infection by Reverse transcription polymerase chain reaction (RT-PCR) or other molecular test within the past 6 days
  3. Current symptoms of acute respiratory infection for ≤6 days, defined as one or more of the following: cough, fever, shortness of breath, chest pain, abdominal pain, nausea/vomiting, diarrhea, body aches, weakness/fatigue, chills/sweating, headache, confusion, sore throat, runny nose/congestion, loss of taste or smell

Exclusion Criteria:

  1. Prisoner
  2. Pregnancy
  3. Breast feeding
  4. Unable to randomize within 6 days after onset of acute respiratory infection symptoms
  5. Hospitalization within the 6 days prior to randomization
  6. Inability to receive enteral medications
  7. Refusal or inability to be contacted and participate in daily symptom/safety monitoring in English or Spanish during the two-week follow-up period
  8. Previous enrollment in this trial
  9. Known severe chronic kidney disease requiring dialysis
  10. Known severe liver disease [cirrhosis or >5 times upper limit of normal for aspartate aminotransferase (AST) or alanine aminotransferease (ALT)]
  11. Known seizure disorder
  12. Known HIV infection
  13. Known history of pancreatitis
  14. Known porphyria cutanea tarda
  15. Known history of prolonged QT interval [Long QT Syndrome, patient report, or (corrected QT interval) QTc >500 milliseconds on most recently available electrocardiogram within the past 2 years]
  16. Known history of ventricular arrhythmia
  17. Known history of unexplained syncope or family history of premature sudden cardiac death
  18. Receipt of >1 dose of hydroxychloroquine, chloroquine, or lopinavir/ritonavir in the 10 days prior to enrollment
  19. Known allergy to hydroxychloroquine, chloroquine, amodiaquine, or lopinavir/ritonavir
  20. Currently prescribed (with planned continuation) or planned administration during 14-day study period of medication at high risk for QT prolongation as follows:

    Antiarrhythmics: Amiodarone, disopyramide, dofetilide, dronedarone, flecainide, ibutilide, procainamide, propafenone, quinidine, sotalol Anti-cancer: Arsenic trioxide, oxaliplatin, vandetanib Antidepressants: Amitriptyline, citalopram, escitalopram, imipramine Antimicrobials: azithromycin, ciprofloxacin, clarithromycin, erythromycin, fluconazole, levofloxacin, moxifloxacin, pentamidine Antipsychotics: aloperidol, chlorpromazine, droperidol, olanzapine, pimozide, quetiapine, thioridazine, risperidone, ziprasidone Others: cilostazol, cimetidine, cisapride, donepezil, methadone, ondansetron, sumatriptan

  21. Currently prescribed (with planned continuation) or planned administration during 14-day study period of any of the following medications: alfuzosin, apalutamide, astemizole, ergot-containing medicines (including dihydroergotamine mesylate, ergotamine tartrate, methylergonovine), lomitapide, lovastatin, lurasidone, midazolam, phenobarbital, phenytoin, ranolazine, rifampin, sildenafil, simvastatin, St. John's Wort, terfenadine, triazolam

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04372628


Contacts
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Contact: Margaret Hays 615-322-3412 margaret.hays@vumc.org

Locations
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United States, Colorado
University of Colorado School of Medicine
Aurora, Colorado, United States, 80045
Contact: Lani L. Finck    303-724-4655    lani.finck@cuanschutz.edu   
Principal Investigator: Adit A Ginde, MD         
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Contact: Nathan I. Shapiro, M.D.    617-754-2343    nshapiro@bidmc.harvard.edu   
Contact: Sharon Hayes, RN    617-754-2334    srhayes@bidmc.harvard.edu   
Principal Investigator: Nathan L Shapiro, MD         
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37203
Contact: Todd W. Rice, M.D.    615-322-3412    todd.rice@vumc.org   
Contact: Margaret A. Hays    (615) 322-3412    margaret.hays@vumc.org   
Principal Investigator: Todd W. Rice, MD         
Sponsors and Collaborators
Vanderbilt University Medical Center
AbbVie
Investigators
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Principal Investigator: Todd Rice, MD Vanderbilt University Medical Center
Additional Information:
Publications:

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Responsible Party: Todd Rice, Associate Professor of Medicine, Vanderbilt University Medical Center
ClinicalTrials.gov Identifier: NCT04372628    
Other Study ID Numbers: 200827
First Posted: May 4, 2020    Key Record Dates
Last Update Posted: May 19, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Todd Rice, Vanderbilt University Medical Center:
Coronavirus
Additional relevant MeSH terms:
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Ritonavir
Lopinavir
Hydroxychloroquine
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Antirheumatic Agents