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COVID-19 Ring-based Prevention Trial With Lopinavir/Ritonavir (CORIPREV-LR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04321174
Recruitment Status : Recruiting
First Posted : March 25, 2020
Last Update Posted : April 21, 2020
Sponsor:
Information provided by (Responsible Party):
Darrell Tan, St. Michael's Hospital, Toronto

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Coronavirus Infections Post-exposure Prophylaxis Drug: Lopinavir/ritonavir Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1220 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Prevention
Official Title: COVID-19 Ring-based Prevention Trial With Lopinavir/Ritonavir
Actual Study Start Date : April 17, 2020
Estimated Primary Completion Date : March 31, 2021
Estimated Study Completion Date : March 31, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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 Names:
  • Kaletra
  • Aluvia

No Intervention: Control
This arm will receive no intervention.



Primary Outcome Measures :
  1. Microbiologic evidence of infection [ Time Frame: 14 days ]
    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.


Secondary Outcome Measures :
  1. Adverse events [ Time Frame: 90 days ]
    a) Adverse events: as defined using the DAIDS Table for Grading the Severity of Adverse Events, at 7, 14, 28 & 90 days

  2. Symptomatic COVID-19 disease [ Time Frame: 14 days ]
    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.

  3. Seropositivity [ Time Frame: 28 days ]
    Reactive serology to SARS-CoV-2

  4. Days of hospitalization attributable to COVID-19 disease [ Time Frame: 90 days ]
    The number of days (or partial days) spent admitted to an acute care hospital will be tabulated both at day 28 and day 90

  5. Respiratory failure requiring ventilatory support attributable to COVID-19 disease [ Time Frame: 90 days ]
    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.

  6. Mortality [ Time Frame: 90 days ]
    Death attributable to COVID-19 disease and all-cause mortality

  7. Short-term psychological impact of exposure to COVID-19 disease [ Time Frame: 28 days ]
    Short-term psychological distress will be measured using the K10, with a standard cutoff score of ≥16.

  8. Long-term psychological impact of exposure to COVID-19 disease [ Time Frame: 90 days ]
    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

  9. Health-related quality of life [ Time Frame: 90 days ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Months and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04321174


Contacts
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Contact: Attia Qamar, BEng 416-864-6060 ext 77325 Attia.Qamar@unityhealth.to
Contact: Alex Schnubb 4168646060 ext 77105 Alexandre.Schnubb@unityhealth.to

Locations
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Canada, British Columbia
St. Paul's Hospital Not yet recruiting
Vancouver, British Columbia, Canada, V6Z 1Y6
Contact: Natasha Press, MD    604-806-8642    npress@cfenet.ubc.ca   
Canada, Ontario
Sunnybrook Hospital Not yet recruiting
Toronto, Ontario, Canada, M4N 3M5
Contact: Adrienne Chan, MD MPH FRCPC       adrienne.chan@sunnybrook.ca   
St. Michael's Hospital Recruiting
Toronto, Ontario, Canada, M5B 1W8
Contact: Darrell Tan, MD PhD FRCPC    416-864-5568      
Principal Investigator: Darrell Tan, MD PhD FRCPC         
Toronto General Hospital Not yet recruiting
Toronto, Ontario, Canada, M5G 2N2
Contact: Sharon Walmsley, MD    4163403871    sharon.walmsley@uhn.com   
Principal Investigator: Sharon Walmsley, MD         
Sponsors and Collaborators
Darrell Tan
Investigators
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Principal Investigator: Darrell Tan, MD FRCPC PhD St. Michael's Hospital, Toronto
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Responsible Party: Darrell Tan, Clinician-Scientist, St. Michael's Hospital, Toronto
ClinicalTrials.gov Identifier: NCT04321174    
Other Study ID Numbers: CORIPREV-1
First Posted: March 25, 2020    Key Record Dates
Last Update Posted: April 21, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: TBA

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Coronavirus Infections
Severe Acute Respiratory Syndrome
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Ritonavir
Lopinavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors