Trial of Early Therapies During Non-hospitalized Outpatient Window for COVID-19
Trial of Early Therapies During Non-hospitalized Outpatient Window for COVID-19
Blinded, multicenter, placebo-controlled, randomized clinical trial evaluating
 lopinavir/ritonavir vs placebo in early outpatient treatment of adults with COVID-19
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.
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.