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COVID-19 Ring-based Prevention Trial With Lopinavir/Ritonavir

Trial Profile

COVID-19 Ring-based Prevention Trial With Lopinavir/Ritonavir

Status: Recruiting
Phase of Trial: Phase III

Latest Information Update: 22 Apr 2020

At a glance

  • Drugs Lopinavir/ritonavir (Primary)
  • Indications COVID 2019 infections
  • Focus Therapeutic Use
  • Acronyms CORIPREV-LR
  • Most Recent Events

    • 17 Apr 2020 Status changed from not yet recruiting to recruiting.
    • 27 Mar 2020 New trial record

Trial Overview

Purpose

COVID-19 has rapidly evolved into a generalized global pandemic. Post-exposure prophylaxis (PEP) against on COVID-19 was identified as an urgent research priority by the WHO, and lopinavir/ritonavir (LPV/r) is a promising candidate for both COVID-19 treatment and PEP, with a good safety profile and global availability. This is a cluster randomized controlled trial (RCT) of oral LPV/r as PEP against COVID-19, that will address the immediate need for preventive interventions, generate key data on COVID-19 transmission, and serve as a research platform for future vaccines and preventive agents.

Primary Endpoints

Microbiologic evidence of infection

description: The primary outcome is microbiologically confirmed COVID-19 infection, ie. detection of viral RNA in a respiratory specimen (mid-turbinate swab, nasopharyngeal swab, sputum specimen, saliva specimen, oral swab, endotracheal aspirate, bronchoalveolar lavage specimen) by day 14 of the study.
time_frame: 14 days

Other Endpoints

Adverse events

description: a) Adverse events: as defined using the DAIDS Table for Grading the Severity of Adverse Events, at 7, 14, 28 & 90 days
time_frame: 90 days

Symptomatic COVID-19 disease

description: fever, cough or other respiratory/ systemic symptoms (including but not limited to fatigue, myalgias, arthralgias, shortness of breath, sore throat, headache, chills, coryza, nausea, vomiting, diarrhea) by day 14 in a patient with laboratory confirmed infection, combined with microbiologic confirmation of COVID-19 infection in the participant.
time_frame: 14 days

Seropositivity

description: Reactive serology to SARS-CoV-2
time_frame: 28 days

Days of hospitalization attributable to COVID-19 disease

description: The number of days (or partial days) spent admitted to an acute care hospital will be tabulated both at day 28 and day 90
time_frame: 90 days

Respiratory failure requiring ventilatory support attributable to COVID-19 disease

description: The number of days (or partial days) requiring i) non-invasive and ii) endotracheal intubation with ventilation will be tabulated both at day 28 and day 90.
time_frame: 90 days

Mortality

description: Death attributable to COVID-19 disease and all-cause mortality
time_frame: 90 days

Short-term psychological impact of exposure to COVID-19 disease

description: Short-term psychological distress will be measured using the K10, with a standard cutoff score of ≥16.
time_frame: 28 days

Long-term psychological impact of exposure to COVID-19 disease

description: Long-term impact will be measured at day 90 using the Impact of Event Scale, a validated measure of traumatic stress response, using a standard cutoff score of ≥26
time_frame: 90 days

Health-related quality of life

description: Health-related quality of life will be measured using the EQ-5D-5L (EuroQol-5D). The EQ-5D consists of two pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The tool will be administered to participants at 1, 14, 28 and 90 days.
time_frame: 90 days [1]

Diseases Treated

Indication Qualifiers Patient Segments
COVID 2019 infections prevention -

Subjects

  • Subject Type patients
  • Number

    Planned: 1220

  • Sex male & female
  • Age Group ≥ 18 months; adolescent; adult; child; infant

Patient Inclusion Criteria

1. High risk close contact with a confirmed COVID-19 case during their symptomatic period, including one day before symptom onset, within the past 1-7 days. High risk close contact is defined as any of the following exposures without the consistent appropriate use of recommended personal protective equipment: 1. Provided direct care for the index case 2. Had close physical contact with the index case 3. Lived with the index case 4. Had close contact (within 2 metres), without direct physical contact, for a prolonged period of time 5. Had direct contact with infectious body fluids, including oral secretions, respiratory secretions, or stool. 2. Successfully contacted by the study team within 24 hours of study team notification of the relevant index COVID-19 case. This time window is necessary because the efficacy of PEP may be dependent on the timing of its initiation, and because randomization of a ring cannot be delayed while awaiting response from contacts that cannot be rapidly reached. 3. Age ≥6 months, since the safety and pharmacokinetic profiles of LPV/r in pediatric patients below the age of 6 months have not been established. 4. Ability to communicate with study staff in English

Patient Exclusion Criteria

1. Known hypersensitivity/allergy to lopinavir or ritonavir. 2. Current use of LPV/r for the treatment or prevention of HIV infection. 3. Receipt of LPV/r in the context of this trial or any other trial of COVID-19 PEP within 2 days or less prior to the last known contact with the index COVID-19 case. The two day time window is intended to ensure that exposure would not have occurred in the presence of clinically relevant drug levels (five times the elimination half-life of LPV/r, which is estimated at 4-6 hours with prolonged use). 4. Baseline respiratory tract specimen positive for COVID-19. Randomized participants whose baseline samples subsequently show COVID-19 will have study drug discontinued but still remain under observation. 5. Current breastfeeding, due to potential for serious adverse reactions in nursing infants exposed to LPV/r 6. Concomitant medications with prohibited drug interactions with LPV/r that cannot be temporarily suspended/replaced, including but not restricted to: 37 - alfuzosin (e.g. Xatral®) - amiodarone (e.g. Cordarone™) - apalutamide (e.g. Erleada™) - astemizole*, terfenadine* - cisapride* - colchicine, when used in patients with renal and/or hepatic impairment - dronedarone (e.g., Multaq®) - elbasvir/grazoprevir (e.g., ZepatierTM) - ergotamine* (e.g. Cafergot®*), dihydroergotamine (e.g. Migranal®), ergonovine, methylergonovine* - fusidic acid (e.g., Fucidin®), systemic* - lurasidone (e.g., Latuda®), pimozide (e.g., Orap®*) - neratinib (e.g., Nerlynx®) - sildenafil (e.g., Revatio®) - triazolam (e.g. Halcion®), midazolam oral* - rifampin (e.g. Rimactane®*, Rifadin®, Rifater®*, Rifamate®*) - St. John's Wort - Tadalafil (e.g. Adcirca®) - venetoclax (e.g. Venclexta®) - lovastatin (e.g., Mevacor®*), lomitapide (e.g., JuxtapidTM) or simvastatin (e.g., Zocor®) - vardenafil (e.g., Levitra® or Staxyn®) - salmeterol (e.g., Advair® or Serevent®) - denotes products not marketed in Canada

Trial Details

Identifiers

Identifier Owner
NCT04321174 ClinicalTrials.gov: US National Institutes of Health
CORIPREV1 -

Trial Dates

  • Initiation Dates

    Planned : 30 Mar 2020

    Actual : 17 Apr 2020

  • Primary Completion Dates

    Planned : 31 Mar 2021

  • End Dates

    Planned : 31 Mar 2022

Other Details

  • Design multicentre; open; parallel; prospective; randomised
  • Phase of Trial Phase III
  • Location Canada
  • Focus Therapeutic Use

Interventions

Drugs Route Formulation
Lopinavir/ritonavirPrimary Drug Oral Tablet

Lopinavir/ritonavir

This arm will receive oral lopinavir/ritonavir 400/100 mg (or equivalent weight-based dosing) twice daily for 14 days.
Drug: Lopinavir/ritonavir (The intervention is a 14-day course of LPV/r 400/100 mg orally twice daily, or equivalent weight-based dosing, to be initiated as soon as possible (within 1-7 days) after the last exposure.) Other Name: Kaletra, Aluvia

Control

This arm will receive no intervention.

Trial Centres

Investigators

Investigator Centre Name Trial Centre Country
Adrienne Chan, MD MPH FRCPC
adrienne.chan@sunnybrook.ca
show details
Sunnybrook Hospital Canada
Alex Schnubb
4168646060 Ext: 77105 Alexandre.Schnubb@unityhealth.to
show details
-
Attia Qamar, BEng
416-864-6060 Ext: 77325 Attia.Qamar@unityhealth.to
show details
-
Darrell Tan, MD FRCPC PhD St. Michael's Hospital, Toronto
-
Darrell Tan, MD PhD FRCPC
416-864-5568
show details
St. Michael's Hospital Canada
Natasha Press, MD
604-806-8642 npress@cfenet.ubc.ca
show details
St. Paul's Hospital Canada
Sharon Walmsley, MD
4163403871 sharon.walmsley@uhn.com
show details
Toronto General Hospital Canada

Centres

Centre Name Location Trial Centre Country
-
-
-
Darrell Tan
-
-
St. Michael's Hospital Toronto, Ontario Canada
St. Michael's Hospital, Toronto
-
-
St. Paul's Hospital Vancouver, British Columbia Canada
Sunnybrook Hospital Toronto, Ontario Canada
Toronto General Hospital Toronto, Ontario Canada

Trial History

Event Date Event Type Comment
22 Apr 2020 Other trial event Last checked against ClinicalTrials.gov record. Updated 22 Apr 2020
17 Apr 2020 Status change - recruiting Status changed from not yet recruiting to recruiting. Updated 22 Apr 2020
27 Mar 2020 New trial record New trial record Updated 27 Mar 2020

References

  1. ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2016;.

    Available from: URL: http://clinicaltrials.gov
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