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

COVID-19 Clinical Trial

— TREATNOW  

Official title:

Trial of Early Therapies During Non-hospitalized Outpatient Window (TREAT NOW) for COVID-19

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04372628
• Other study ID #: 200827
• Status: Completed
• Phase: Phase 2
• Start date: June 1, 2020
• Est. completion date: January 18, 2022

Study information

• Verified date: February 2024
• Source: Vanderbilt University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 452
• Est. completion date: January 18, 2022
• Est. primary completion date: December 16, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• Lopinavir/Ritonavir 400 mg/100 mg
Lopinavir/Ritonavir tablets

Other:
• Placebo
Unmatched placebo

Locations

Country	Name	City	State
United States	University of Colorado School of Medicine	Aurora	Colorado
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	University of Wisconsin	Madison	Wisconsin
United States	Intermountain	Murray	Utah
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center	AbbVie

Country where clinical trial is conducted

United States, 

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* Note: There are 34 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Modified COVID Ordinal Outcomes Scale: Study Day 15 (Group 2 and Placebo Control Group)	Improvement of clinical condition of the participant defined by the Modified COVID Ordinal Outcomes Scale (Modified from the COVID-19 WHO ordinal Outcomes score to fit the outpatient setting). This scale reflects a range of participants from dead to not hospitalized and with no limitations to activities of daily living. A score of 1 is "death", 2 is "Hospitalized on mechanical ventilation or extracorporeal membrane oxygenator (ECMO)", 3 is "Hospitalized on supplemental oxygen", 4 is "Hospitalized not on supplemental oxygen", 5 is "Not hospitalized with symptoms and limitation in activity", 6 is "Not hospitalized with symptoms but with no limitation in activity", 7 is "Not hospitalized without symptoms nor limitation in activity". COVID outcomes are more severe at the lower end of the scale and milder at the higher end of the scale for this outpatient trial.	Day 1 to Day 15
Secondary	Modified COVID Ordinal Outcome Scale: Study Day 8 (Group 2 and Placebo Control Group)	Improvement of clinical condition of the participant defined by the Modified COVID Ordinal Outcomes Scale (Modified from the COVID-19 WHO ordinal Outcomes score to fit the outpatient setting). This scale reflects a range of participants from dead to not hospitalized and with no limitations to activities of daily living. A score of 1 is "death", 2 is "Hospitalized on mechanical ventilation or extracorporeal membrane oxygenator (ECMO)", 3 is "Hospitalized on supplemental oxygen", 4 is "Hospitalized not on supplemental oxygen", 5 is "Not hospitalized with symptoms and limitation in activity", 6 is "Not hospitalized with symptoms but with no limitation in activity", 7 is "Not hospitalized without symptoms nor limitation in activity". COVID outcomes are more severe at the lower end of the scale and milder at the higher end of the scale for this outpatient trial.	on or at Day 8
Secondary	Modified COVID Ordinal Outcome Scale: Study Day 29 (Group 2 and Placebo Control Group)	Improvement of clinical condition of the participant defined by the Modified COVID Ordinal Outcomes Scale (Modified from the COVID-19 WHO ordinal Outcomes score to fit the outpatient setting). This scale reflects a range of participants from dead to not hospitalized and with no limitations to activities of daily living. A score of 1 is "death", 2 is "Hospitalized on mechanical ventilation or extracorporeal membrane oxygenator (ECMO)", 3 is "Hospitalized on supplemental oxygen", 4 is "Hospitalized not on supplemental oxygen", 5 is "Not hospitalized with symptoms and limitation in activity", 6 is "Not hospitalized with symptoms but with no limitation in activity", 7 is "Not hospitalized without symptoms nor limitation in activity". COVID outcomes are more severe at the lower end of the scale and milder at the higher end of the scale for this outpatient trial.	on or at Day 29
Secondary	Number of Patients Hospitalized: Day 1 to 29 (Group 2 and Placebo Control Group)	Number of patients hospitalized from Day 1 to 29 (Group 2 and Placebo Control Group)	Day 1 to Day 29
Secondary	Time to Hospitalization Day 1 to Day 29 (Group 2 and Placebo Control Group)	Number of days from enrollment to hospitalization (Group 2 and Placebo Control Group)	Day 1 to Day 29
Secondary	Time to Symptom Resolution: Day 1 to Day 29 (Group 2 and Placebo Control Group)	Number of days from enrollment to resolution of COVID-19 symptoms (Group 2 and Placebo Control Group)	Day 1 to Day 29
Secondary	All-cause, All-location Mortality: Day 1 to Day 29 (Group 2 and Placebo Control Group)	Survival status (All-cause, all-location mortality) from Day 1 to Day 29 (Group 2 and Placebo Control Group)	Day 1 to Day 29
Secondary	Oxygen-free Days: Day 1 to Day 29 (Group 2 and Placebo Control Group)	Number of Days without oxygen Day 1 to Day 29 (Group 2 and Placebo Control Group)	Day 1 to Day 29
Secondary	Fever-free Days: Day 1 to Day 29 (Group 2 and Placebo Control Group)	Number of days without fever from Day 1 to Day 29 (Group 2 and Placebo Control Group)	Day 1 to Day 29
Secondary	Ventilator-free Days: Day 1 to Day 29 (Group 2 and Placebo Control Group)	Number of days without ventilator use from Day 1 to Day 29 (Group 2 and Placebo Control Group)	Day 1 to Day 29
Secondary	ICU-free Days: Day 1 to Day 29 (Group 2 and Placebo Control Group)	Number of days outside the ICU from Day 1 to Day 29 (Group 2 and Placebo Control Group)	Day 1 to Day 29
Secondary	Hospital-free Days: Day 1 to Day 29 (Group 2 and Placebo Control Group)	Number of days outside the hospital from Day 1 to Day 29 (Group 2 and Placebo Control Group)	Day 1 to Day 29
Secondary	Vasopressor-free Days Through Study Day 29 (Group 2 and Placebo Control Group)	Number of vasopressor-free days through Study Day 29 (Group 2 and Placebo Control Group)	Day 1 to Day 29

External Links

•   Hydroxychloroquine [Internet]. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012 [cited 2020 Mar 21].
•   WHO | Coronavirus disease (COVID-2019) R&D [Internet]. WHO. [cited 2020 Mar 18];
•   Woosley R, Heise C, Gallo T, Tate J, Woosley D, Romero K. www.CredibleMeds.org, QTdrugs ListCredibleMeds [Internet]. [cited 2020 Apr 24]
•   World Health Organization (WHO). WHO R&D Blueprint: informal consultation on prioritization of candidate therapeutic agents for use in novel coronavirus 2019 infection, Geneva, Switzerland, 24 January 2020. [Internet]. [cited 2020 Mar 19]