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

Study Overview
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Brief Summary
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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.

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

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

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Lopinavir/ritonavir
* Drug: Hydroxychloroquine sulfate


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multicenter, open labelled, randomized clinical trial
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 |