Comparison of Lopinavir/Ritonavir or Hydroxychloroquine in Patients With Mild Coronavirus Disease (COVID-19)

Randomized Controlled Clinical Trials of Lopinavir/Ritonavir or Hydroxychloroquine in Patients With Mild Coronavirus Disease (COVID-19)

In vitro studies revealed that lopinavir/ritonavir and hydroxychloroquine have antiviral activity against Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there is no clinical studies on the reduction of viral load in patients with COVID-19. This study investigate whether lopinavir/ritonavir or hydroxychloroquine reduces viral load from respiratory specimen in patients with mild COVID-19.

Study Overview

• Status: Terminated
• Conditions: COVID-19
• Intervention / Treatment: Drug: Lopinavir/ritonavir; Drug: Hydroxychloroquine sulfate

Detailed Description

This multicenter study is an open-labelled, randomized clinical trial for 1:1:1 ratio of lopinavir/ritonavir, hydroxychloroquine, or control arm.

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center, University of Ulsan College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 99 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• confirmed mild COVID-19 (NEWS scoring system 0-4)

Exclusion Criteria:

• unable to take oral medication
• pregnancy or breast feeding
• immunocompromised patients
• creatinine clearance (CCL) < 30 mL/min
• aspartate transaminase (AST) or alanine transaminase (ALT) > 5 times Upper limit of normal (ULN)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lopinavir/ritonavir; Lopinavir/ritonavir 200mg/100mg 2 tablets by mouth, every 12 hours for 7-10 days	Drug: Lopinavir/ritonavir; Lopinavir / Ritonavir tablet; Other Names: Kaletra
Active Comparator: Hydroxychloroquine; Hydroxychloroquine 400mg by mouth, every 24 hours for 7-10 days	Drug: Hydroxychloroquine sulfate; Hydroxychloroquine sulfate tablet; Other Names: Oxiklorin
No Intervention: Control; No lopinavir/ritonavir and hydroxychloroquine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Viral load	Area under the curve (AUC) of Ct value or viral copies number per mL	hospital day 3, 5, 7, 10, 14, 18

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Viral load change	Viral load change (log10 viral load assessed by reverse transcription-PCR) during hospital day 3, 5, 7, 10, 14, 18)	hospital day 3, 5, 7, 10, 14, 18
Time to clinical improvement (TTCI)	Time to clinical improvement (TTCI) is defined as the time to normalization of fever, respiratory rate, and oxygen saturation, and alleviation of cough within at least 72 hours	up to 28 days
Percentage of progression to supplemental oxygen requirement by day 7	Percentage of progression to supplemental oxygen requirement by day 7	hospital day 7
Time to NEWS2 (National Early Warning Score 2) of 3 or more maintained for 24 hours by day 7	Time to NEWS2 (National Early Warning Score 2) of 3 or more maintained for 24 hours by day 7	hospital day 7
Time to clinical failure, defined as the time to death, mechanical ventilation, or ICU admission	Time to clinical failure, defined as the time to death, mechanical ventilation, or ICU admission	up to 28 days
Rate of switch to Lopinavir/ritonavir or hydroxychloroquine by day 7	Rate of switch to Lopinavir/ritonavir or hydroxychloroquine by day 7	hospital day 7
adverse effects	Safety and tolerability, as assessed by adverse effects	up to 28 days
Concentration of Lopinavir/ritonavir and hydroxychloroquine	Concentration of Lopinavir/ritonavir and hydroxychloroquine	1, 2, 4, 5, 12 hours after taking intervention medicine

Collaborators and Investigators

• Sponsor: Asan Medical Center

Publications and helpful links

General Publications

• Lipsitch M, Perlman S, Waldor MK. Testing COVID-19 therapies to prevent progression of mild disease. Lancet Infect Dis. 2020 Dec;20(12):1367. doi: 10.1016/S1473-3099(20)30372-8. Epub 2020 May 6. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2020
• Primary Completion (Actual): April 30, 2020
• Study Completion (Actual): April 30, 2020

Study Registration Dates

• First Submitted: March 10, 2020
• First Submitted That Met QC Criteria: March 12, 2020
• First Posted (Actual): March 13, 2020

Study Record Updates

• Last Update Posted (Actual): May 27, 2020
• Last Update Submitted That Met QC Criteria: May 25, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antirheumatic Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; HIV Protease Inhibitors; Viral Protease Inhibitors; Antimalarials; Ritonavir; Lopinavir; Hydroxychloroquine
• Other Study ID Numbers: S2020-0472-0001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No