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

Coronavirus Infections Clinical Trial

— CORIPREV-LR  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04321174
• Other study ID #: CORIPREV-1
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: April 17, 2020
• Est. completion date: March 31, 2022

Study information

• Verified date: November 2021
• Source: Unity Health Toronto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 123
• Est. completion date: March 31, 2022
• Est. primary completion date: August 27, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Months and older

Eligibility

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

Related Conditions & MeSH terms

• Coronavirus Infections
• Post-exposure Prophylaxis

Intervention

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.

Locations

Country	Name	City	State
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	Sunnybrook Hospital	Toronto	Ontario
Canada	Toronto General Hospital	Toronto	Ontario
Canada	St. Paul's Hospital	Vancouver	British Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Unity Health Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Adverse events	a) Adverse events: as defined using the DAIDS Table for Grading the Severity of Adverse Events, at 7, 14, 28 & 90 days	90 days
Secondary	Symptomatic COVID-19 disease	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.	14 days
Secondary	Seropositivity	Reactive serology to SARS-CoV-2	28 days
Secondary	Days of hospitalization attributable to COVID-19 disease	The number of days (or partial days) spent admitted to an acute care hospital will be tabulated both at day 28 and day 90	90 days
Secondary	Respiratory failure requiring ventilatory support attributable to COVID-19 disease	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.	90 days
Secondary	Mortality	Death attributable to COVID-19 disease and all-cause mortality	90 days
Secondary	Short-term psychological impact of exposure to COVID-19 disease	Short-term psychological distress will be measured using the K10, with a standard cutoff score of =16.	28 days
Secondary	Long-term psychological impact of exposure to COVID-19 disease	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	90 days
Secondary	Health-related quality of life	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.	90 days