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

NCT ID: NCT04321174

Last Updated: 2021-12-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

123 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-04-17

Study Completion Date

2022-03-31

Brief Summary

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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.

Detailed Description

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Conditions

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Coronavirus Infections Post-exposure Prophylaxis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Lopinavir/ritonavir

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

Group Type EXPERIMENTAL

Lopinavir/ritonavir

Intervention Type DRUG

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.

Control

This arm will receive no intervention.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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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.

Intervention Type DRUG

Other Intervention Names

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Kaletra Aluvia

Eligibility Criteria

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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
Minimum Eligible Age

18 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Unity Health Toronto

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Darrell Tan, MD FRCPC PhD

Role: PRINCIPAL_INVESTIGATOR

Unity Health Toronto

Locations

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St. Paul's Hospital

Vancouver, British Columbia, Canada

Site Status

Sunnybrook Hospital

Toronto, Ontario, Canada

Site Status

St. Michael's Hospital

Toronto, Ontario, Canada

Site Status

Toronto General Hospital

Toronto, Ontario, Canada

Site Status

Countries

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Canada

References

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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.

Reference Type DERIVED
PMID: 33752741 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33570583 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33240091 (View on PubMed)

Other Identifiers

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CORIPREV-1

Identifier Type: -

Identifier Source: org_study_id