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

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.