Overview
Blinded, multicenter, placebo-controlled, randomized clinical trial evaluating lopinavir/ritonavir vs placebo in early outpatient treatment of adults with COVID-19
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.
Eligibility
Inclusion Criteria:
- Age 18 years
- 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
- 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, chills/sweating, headache, confusion, sore throat, runny nose/congestion, loss of taste or smell
Exclusion Criteria:
- Prisoner
- Pregnancy
- Breast feeding
- Two individuals from the same household are not enrolled in the study
- Unable to randomize within 6 days after onset of acute respiratory infection symptoms
- Hospitalization within the 6 days prior to randomization
- Inability to swallow oral medications
- Refusal or inability to be contacted and participate in daily symptom/safety monitoring in English or Spanish during the two-week follow-up period
- Previous enrollment in this trial
- Known severe chronic kidney disease requiring dialysis
- Known severe liver disease [cirrhosis or >5 times upper limit of normal for aspartate aminotransferase (AST) or alanine aminotransferase (ALT)]
- Known hepatitis B or hepatitis C infection
- Known history of jaundice
- Current heavy alcohol use, defined as 8 drinks or more per week for women or 15 drinks or more per week for men
- Known seizure disorder
- Known HIV infection
- Known history of pancreatitis
- 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]
- Receipt of >1 dose of hydroxychloroquine, chloroquine, or lopinavir/ritonavir in the 10 days prior to enrollment
- Known allergy to lopinavir/ritonavir
- 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