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

Purpose

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

Condition

  • COVID-19

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
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 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 Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Sequential Assignment
Intervention Model Description
Blinded, multicenter, placebo-controlled randomized clinical trial
Primary Purpose
Treatment
Masking
Triple (Participant, Care Provider, Investigator)
Masking Description
Lopinavir/Ritonavir tablets or unmatched placebo tablets

Arm Groups

ArmDescriptionAssigned Intervention
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

Recruiting Locations

Vanderbilt University Medical Center
Nashville, Tennessee 37203
Contact:
Todd W. Rice, M.D.
615-322-3412
todd.rice@vumc.org

More Details

Status
Recruiting
Sponsor
Vanderbilt University Medical Center

Study Contact

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

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.