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

February 23, 2024 updated by: Todd Rice, Vanderbilt University Medical Center

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

452

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado School of Medicine
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • University of Mississippi Medical Center
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Vanderbilt University Medical Center
    • Utah
      • Murray, Utah, United States, 84107
        • Intermountain
    • Wisconsin
      • Madison, Wisconsin, United States, 53705
        • University of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

  22. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Modified COVID Ordinal Outcomes Scale: Study Day 15 (Group 2 and Placebo Control Group)
Time Frame: Day 1 to Day 15
Improvement of clinical condition of the participant defined by the Modified COVID Ordinal Outcomes Scale (Modified from the COVID-19 WHO ordinal Outcomes score to fit the outpatient setting). This scale reflects a range of participants from dead to not hospitalized and with no limitations to activities of daily living. A score of 1 is "death", 2 is "Hospitalized on mechanical ventilation or extracorporeal membrane oxygenator (ECMO)", 3 is "Hospitalized on supplemental oxygen", 4 is "Hospitalized not on supplemental oxygen", 5 is "Not hospitalized with symptoms and limitation in activity", 6 is "Not hospitalized with symptoms but with no limitation in activity", 7 is "Not hospitalized without symptoms nor limitation in activity". COVID outcomes are more severe at the lower end of the scale and milder at the higher end of the scale for this outpatient trial.
Day 1 to Day 15

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Modified COVID Ordinal Outcome Scale: Study Day 8 (Group 2 and Placebo Control Group)
Time Frame: on or at Day 8
Improvement of clinical condition of the participant defined by the Modified COVID Ordinal Outcomes Scale (Modified from the COVID-19 WHO ordinal Outcomes score to fit the outpatient setting). This scale reflects a range of participants from dead to not hospitalized and with no limitations to activities of daily living. A score of 1 is "death", 2 is "Hospitalized on mechanical ventilation or extracorporeal membrane oxygenator (ECMO)", 3 is "Hospitalized on supplemental oxygen", 4 is "Hospitalized not on supplemental oxygen", 5 is "Not hospitalized with symptoms and limitation in activity", 6 is "Not hospitalized with symptoms but with no limitation in activity", 7 is "Not hospitalized without symptoms nor limitation in activity". COVID outcomes are more severe at the lower end of the scale and milder at the higher end of the scale for this outpatient trial.
on or at Day 8
Modified COVID Ordinal Outcome Scale: Study Day 29 (Group 2 and Placebo Control Group)
Time Frame: on or at Day 29
Improvement of clinical condition of the participant defined by the Modified COVID Ordinal Outcomes Scale (Modified from the COVID-19 WHO ordinal Outcomes score to fit the outpatient setting). This scale reflects a range of participants from dead to not hospitalized and with no limitations to activities of daily living. A score of 1 is "death", 2 is "Hospitalized on mechanical ventilation or extracorporeal membrane oxygenator (ECMO)", 3 is "Hospitalized on supplemental oxygen", 4 is "Hospitalized not on supplemental oxygen", 5 is "Not hospitalized with symptoms and limitation in activity", 6 is "Not hospitalized with symptoms but with no limitation in activity", 7 is "Not hospitalized without symptoms nor limitation in activity". COVID outcomes are more severe at the lower end of the scale and milder at the higher end of the scale for this outpatient trial.
on or at Day 29
Number of Patients Hospitalized: Day 1 to 29 (Group 2 and Placebo Control Group)
Time Frame: Day 1 to Day 29
Number of patients hospitalized from Day 1 to 29 (Group 2 and Placebo Control Group)
Day 1 to Day 29
Time to Hospitalization Day 1 to Day 29 (Group 2 and Placebo Control Group)
Time Frame: Day 1 to Day 29
Number of days from enrollment to hospitalization (Group 2 and Placebo Control Group)
Day 1 to Day 29
Time to Symptom Resolution: Day 1 to Day 29 (Group 2 and Placebo Control Group)
Time Frame: Day 1 to Day 29
Number of days from enrollment to resolution of COVID-19 symptoms (Group 2 and Placebo Control Group)
Day 1 to Day 29
All-cause, All-location Mortality: Day 1 to Day 29 (Group 2 and Placebo Control Group)
Time Frame: Day 1 to Day 29
Survival status (All-cause, all-location mortality) from Day 1 to Day 29 (Group 2 and Placebo Control Group)
Day 1 to Day 29
Oxygen-free Days: Day 1 to Day 29 (Group 2 and Placebo Control Group)
Time Frame: Day 1 to Day 29
Number of Days without oxygen Day 1 to Day 29 (Group 2 and Placebo Control Group)
Day 1 to Day 29
Fever-free Days: Day 1 to Day 29 (Group 2 and Placebo Control Group)
Time Frame: Day 1 to Day 29
Number of days without fever from Day 1 to Day 29 (Group 2 and Placebo Control Group)
Day 1 to Day 29
Ventilator-free Days: Day 1 to Day 29 (Group 2 and Placebo Control Group)
Time Frame: Day 1 to Day 29
Number of days without ventilator use from Day 1 to Day 29 (Group 2 and Placebo Control Group)
Day 1 to Day 29
ICU-free Days: Day 1 to Day 29 (Group 2 and Placebo Control Group)
Time Frame: Day 1 to Day 29
Number of days outside the ICU from Day 1 to Day 29 (Group 2 and Placebo Control Group)
Day 1 to Day 29
Hospital-free Days: Day 1 to Day 29 (Group 2 and Placebo Control Group)
Time Frame: Day 1 to Day 29
Number of days outside the hospital from Day 1 to Day 29 (Group 2 and Placebo Control Group)
Day 1 to Day 29
Vasopressor-free Days Through Study Day 29 (Group 2 and Placebo Control Group)
Time Frame: Day 1 to Day 29
Number of vasopressor-free days through Study Day 29 (Group 2 and Placebo Control Group)
Day 1 to Day 29

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vanderbilt University Medical Center

Collaborators

AbbVie

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2020

Primary Completion (Actual)

December 16, 2021

Study Completion (Actual)

January 18, 2022

Study Registration Dates

First Submitted

April 30, 2020

First Submitted That Met QC Criteria

April 30, 2020

First Posted (Actual)

May 4, 2020

Study Record Updates

Last Update Posted (Actual)

February 28, 2024

Last Update Submitted That Met QC Criteria

February 23, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 200827

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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