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

NCT04372628 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 200827
• Study Type: interventional
• Target: 452
• Locations: 1 country
• Sites: 6

Brief Summary

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

Conditions

COVID-19

Keywords

Coronavirus

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (12)

• Modified COVID Ordinal Outcome Scale: Study Day 8 (Group 2 and Placebo Control Group)

  on or at Day 8

• Modified COVID Ordinal Outcome Scale: Study Day 29 (Group 2 and Placebo Control Group)

  on or at Day 29

• Number of Patients Hospitalized: Day 1 to 29 (Group 2 and Placebo Control Group)

  Day 1 to Day 29

• Time to Hospitalization Day 1 to Day 29 (Group 2 and Placebo Control Group)

  Day 1 to Day 29

• Time to Symptom Resolution: Day 1 to Day 29 (Group 2 and Placebo Control Group)

  Day 1 to Day 29

Study Arms (2)

Group 1 - Lopinavir/Ritonavir

ACTIVE COMPARATOR

Lopinavir/Ritonavir 400 mg/100 mg orally twice daily for twenty-eight doses (Days 1-14)

Drug: Lopinavir/Ritonavir 400 mg/100 mg

Control Group

PLACEBO COMPARATOR

Placebo unmatched orally twice daily for 14 days

Other: Placebo

Interventions

Lopinavir/Ritonavir 400 mg/100 mg DRUG

Lopinavir/Ritonavir tablets

Also known as: Kaletra

Group 1 - Lopinavir/Ritonavir

Placebo OTHER

Unmatched placebo

Control Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 \[cirrhosis or \>3 times upper limit of normal for aspartate aminotransferase (AST) or alanine aminotransferase (ALT) in medical record if available\]
• 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

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• AbbVie: collaborator

Study Sites (6)

University of Colorado School of Medicine

Aurora, Colorado, 80045, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37203, United States

Location

Intermountain

Murray, Utah, 84107, United States

Location

University of Wisconsin

Madison, Wisconsin, 53705, United States

Location

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Related Links

• 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. \[Internet\]. \[cited 2020 Mar 19\]
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• WHO \| Coronavirus disease (COVID-2019) R\&D \[Internet\]. WHO. \[cited 2020 Mar 18\];
• 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 \[cited 2020 Mar 21\].

MeSH Terms

Conditions

COVID-19; Coronavirus Infections

Interventions

Lopinavir; Ritonavir; lopinavir-ritonavir drug combination

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles

Results Point of Contact

• Title: Clinical Trials Operations Manager
• Organization: Vanderbilt University Medical Center

kelly.walsh@vumc.org

(615) 875-3080

Study Officials

• Todd Rice, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Lopinavir/Ritonavir tablets or unmatched placebo tablets
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Model Details: Blinded, multicenter, placebo-controlled randomized clinical trial

Study Record Dates

• First Submitted: April 30, 2020
• First Posted: May 4, 2020
• Study Start: June 1, 2020
• Primary Completion: December 16, 2021
• Study Completion: January 18, 2022
• Last Updated: February 28, 2024
• Results First Posted: January 26, 2023

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)