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TREATNOW: Trial of Early Therapies During Non-hospitalized Outpatient Window for COVID-19

Sponsor
Vanderbilt University Medical Center (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT04372628
Collaborator
AbbVie (Industry)
600
Enrollment
6
Locations
2
Arms
27
Anticipated Duration (Months)
100
Patients Per Site
3.7
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
  • 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 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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
600 participants
Allocation:
Randomized
Intervention Model:
Sequential Assignment
Intervention Model Description:
Blinded, multicenter, placebo-controlled randomized clinical trialBlinded, multicenter, placebo-controlled randomized clinical trial
Masking:
Triple (Participant, Care Provider, Investigator)
Masking Description:
Lopinavir/Ritonavir tablets or unmatched placebo tablets
Primary Purpose:
Treatment
Official Title:
Trial of Early Therapies During Non-hospitalized Outpatient Window (TREAT NOW) for COVID-19
Actual Study Start Date :
Jun 1, 2020
Actual Primary Completion Date :
Dec 16, 2021
Anticipated Study Completion Date :
Sep 1, 2022

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Group 1 - 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 Names:
  • Kaletra

    		•
    Placebo Comparator: Control Group

    Placebo unmatched orally twice daily for 14 days

    Other: Placebo
    Unmatched placebo

    Outcome Measures

    Primary Outcome Measures

    1. Modified COVID Ordinal Outcomes Scale: Study Day 15 [Day 15]

      Death Hospitalized on mechanical ventilation or extracorporeal membrane oxygenator (ECMO) Hospitalized on supplemental oxygen Hospitalized not on supplemental oxygen Not hospitalized with symptoms and limitation in activity Not hospitalized with symptoms but with no limitation in activity 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 [Day 8]

      Death Hospitalized on mechanical ventilation or ECMO Hospitalized on supplemental oxygen Hospitalized not on supplemental oxygen Not hospitalized with symptoms and limitation in activity Not hospitalized with symptoms but with no limitation in activity Not hospitalized without symptoms nor limitation in activity

    2. Modified COVID Ordinal Outcome Scale: Study Day 29 [Day 29]

      Death Hospitalized on mechanical ventilation or ECMO Hospitalized on supplemental oxygen Hospitalized not on supplemental oxygen Not hospitalized with symptoms and limitation in activity Not hospitalized with symptoms but with no limitation in activity Not hospitalized without symptoms nor limitation in activity Ordinal Scale

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

      Proportion hospitalized

    4. Time to hospitalization Day 1 to Day 29 [Day 1 to Day 29]

      Number of days from enrollment to hospitalization

    5. Time to symptom resolution: Day 1 to Day 29 [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 [Day 1 to Day 29]

      Survival status

    7. Oxygen-free days: Day 1 to Day 29 [Day 1 to Day 29]

      Number of Days without oxygen

    8. Fever-free days: Day 1 to Day 29 [Day 1 to Day 29]

      Number of days without fever

    9. Ventilator-free days: Day 1 to Day 29 [Day 1 to Day 29]

      Number of days without ventilator use

    10. ICU-free days: Day 1 to Day 29 [Day 1 to Day 29]

      Number of days outside the ICU

    11. Hospital-free days: Day 1 to Day 29 [Day 1 to Day 29]

      Number of days outside the hospital

    12. Vasopressor-free days through Study Day 29 [Day 1 to Day 29]

      Number of days without vasopressor

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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 collected 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.

    Exclusion Criteria:

    1. Prisoner

    2. Pregnancy

    3. Breast feeding

    4. Two individuals from the same household are not enrolled in the study

    5. Unable to randomize within 6 days after onset of acute respiratory infection symptoms

    6. Hospitalization within the 6 days prior to randomization

    7. Inability to swallow oral medications

    8. Refusal or inability to be contacted and participate in daily symptom/safety monitoring in English or Spanish during the two-week follow-up period

    9. Previous enrollment in this trial

    10. Known severe chronic kidney disease requiring dialysis

    11. Known severe liver disease [cirrhosis or >3 times upper limit of normal for aspartate aminotransferase (AST) or alanine aminotransferase (ALT) in medical record if available]

    12. Known hepatitis B or hepatitis C infection

    13. Known history of jaundice

    14. Current heavy alcohol use, defined as 8 drinks or more per week for women or 15 drinks or more per week for men

    15. Known seizure disorder

    16. Known human immunodeficiency virus (HIV) infection

    17. Known history of pancreatitis

    18. 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]

    19. Receipt of >1 dose of lopinavir/ritonavir in the 10 days prior to enrollment

    20. Known allergy to lopinavir/ritonavir

    21. 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, hydroxychloroquine Antipsychotics: haloperidol, chlorpromazine, droperidol, olanzapine, pimozide, quetiapine, thioridazine, risperidone, ziprasidone Others: cilostazol, cimetidine, cisapride, donepezil, methadone, ondansetron, sumatriptan

    1. 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. Patients who are on warfarin or fluticasone will be advised to contact their primary care provider to advise them that they are in the trial and possibly receiving lopinavir/ritonavir which can influence levels of either drug and may require more frequent monitoring.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Colorado School of Medicine Aurora Colorado United States 80045
    2 Beth Israel Deaconess Medical Center Boston Massachusetts United States 02215
    3 University of Mississippi Medical Center Jackson Mississippi United States 39216
    4 Vanderbilt University Medical Center Nashville Tennessee United States 37203
    5 Intermountain Murray Utah United States 84107
    6 University of Wisconsin Madison Wisconsin United States 53705

    Sponsors and Collaborators

    • Vanderbilt University Medical Center
    • AbbVie

    Investigators

    • Principal Investigator: Todd Rice, MD, Vanderbilt University Medical Center

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    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
    Last Update Posted:
    Aug 22, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    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, Associate Professor of Medicine, Vanderbilt University Medical Center
    Coronavirus
    Additional relevant MeSH terms:
    COVID-19
    Ritonavir
    Lopinavir

    Study Results

    No Results Posted as of Aug 22, 2022