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

Vanderbilt University Medical Center

Status and phase: Completed; Phase 2

Conditions: COVID-19

Treatments: Other: Placebo; Drug: Lopinavir/Ritonavir 400 mg/100 mg

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04372628

200827

Details and patient eligibility

About

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

Full 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.

Enrollment: 452 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Triple Blind

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452 participants in 2 patient groups, including a placebo group

Group 1 - Lopinavir/Ritonavir

Active Comparator group

Description:

Lopinavir/Ritonavir 400 mg/100 mg orally twice daily for twenty-eight doses (Days 1-14)

Treatment:

Drug: Lopinavir/Ritonavir 400 mg/100 mg

Control Group

Placebo Comparator group

Description:

Placebo unmatched orally twice daily for 14 days

Treatment:

Other: Placebo