NCT04321174

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
123

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Apr 2020

Geographic Reach
1 country

4 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 18, 2020

Completed
7 days until next milestone

First Posted

Study publicly available on registry

March 25, 2020

Completed
23 days until next milestone

Study Start

First participant enrolled

April 17, 2020

Completed
1.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 27, 2021

Completed
7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 31, 2022

Completed
Last Updated

December 14, 2021

Status Verified

November 1, 2021

Enrollment Period

1.4 years

First QC Date

March 18, 2020

Last Update Submit

November 29, 2021

Conditions

Coronavirus InfectionsPost-exposure Prophylaxis

Outcome Measures

Primary Outcomes (1)

  • Microbiologic evidence of infection

    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.

    14 days

Secondary Outcomes (9)

  • Adverse events

    90 days

  • Symptomatic COVID-19 disease

    14 days

  • Seropositivity

    28 days

  • Days of hospitalization attributable to COVID-19 disease

    90 days

  • Respiratory failure requiring ventilatory support attributable to COVID-19 disease

    90 days

  • +4 more secondary outcomes

Study Arms (2)

Lopinavir/ritonavir

EXPERIMENTAL

This arm will receive oral lopinavir/ritonavir 400/100 mg (or equivalent weight-based dosing) twice daily for 14 days.

Drug: Lopinavir/ritonavir

Control

NO INTERVENTION

This arm will receive no intervention.

Interventions

Lopinavir/ritonavirDRUG

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.

Also known as: Kaletra, Aluvia
Lopinavir/ritonavir

Eligibility Criteria

Age18 Months+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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:
  • Provided direct care for the index case
  • Had close physical contact with the index case
  • Lived with the index case
  • Had close contact (within 2 metres), without direct physical contact, for a prolonged period of time
  • Had direct contact with infectious body fluids, including oral secretions, respiratory secretions, or stool.
  • 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.
  • 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.
  • Ability to communicate with study staff in English

You may not qualify if:

  • Known hypersensitivity/allergy to lopinavir or ritonavir.
  • Current use of LPV/r for the treatment or prevention of HIV infection.
  • 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).
  • 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.
  • Current breastfeeding, due to potential for serious adverse reactions in nursing infants exposed to LPV/r
  • 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\*
  • +13 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

St. Paul's Hospital

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

Sunnybrook Hospital

Toronto, Ontario, M4N 3M5, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Toronto General Hospital

Toronto, Ontario, M5G 2N2, Canada

Location

Related Publications (3)

  • Tan DHS, Chan AK, Juni P, Tomlinson G, Daneman N, Walmsley S, Muller M, Fowler R, Murthy S, Press N, Cooper C, Lee T, Mazzulli T, McGeer A. Post-exposure prophylaxis against SARS-CoV-2 in close contacts of confirmed COVID-19 cases (CORIPREV): study protocol for a cluster-randomized trial. Trials. 2021 Mar 22;22(1):224. doi: 10.1186/s13063-021-05134-7.

    PMID: 33752741DERIVED

  • Akhtar S, Das JK, Ismail T, Wahid M, Saeed W, Bhutta ZA. Nutritional perspectives for the prevention and mitigation of COVID-19. Nutr Rev. 2021 Feb 11;79(3):289-300. doi: 10.1093/nutrit/nuaa063.

    PMID: 33570583DERIVED

  • Sultana J, Crisafulli S, Gabbay F, Lynn E, Shakir S, Trifiro G. Challenges for Drug Repurposing in the COVID-19 Pandemic Era. Front Pharmacol. 2020 Nov 6;11:588654. doi: 10.3389/fphar.2020.588654. eCollection 2020.

    PMID: 33240091DERIVED

MeSH Terms

Conditions

Coronavirus Infections

Interventions

Lopinavirlopinavir-ritonavir drug combination

Condition Hierarchy (Ancestors)

Coronaviridae InfectionsNidovirales InfectionsRNA Virus InfectionsVirus DiseasesInfections

Intervention Hierarchy (Ancestors)

PyrimidinonesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Officials

  • Darrell Tan, MD FRCPC PhD

    Unity Health Toronto

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 18, 2020

First Posted

March 25, 2020

Study Start

April 17, 2020

Primary Completion

August 27, 2021

Study Completion

March 31, 2022

Last Updated

December 14, 2021

Record last verified: 2021-11

Locations

CA(4)