Trial of Early Therapies During Non-hospitalized Outpatient Window for COVID-19
Condition: COVID-19
MeSH terms: COVID-19
Intervention: Lopinavir/Ritonavir 400 mg/100 mg; Placebo
Intervention description: Lopinavir/Ritonavir tablets; Unmatched placebo
Intervention MeSH terms: Ritonavir; Lopinavir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: Blinded, multicenter, placebo-controlled randomized clinical trial
Masking: Triple (Participant, Care Provider, Investigator)
Masking description: Lopinavir/Ritonavir tablets or unmatched placebo tablets
Enrollment: 452.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Coronavirus

Summary:

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

Eligibility 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 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.