Efficacy of Pragmatic Same-day COVID-19 Ring Prophylaxis for Adult Individuals Exposed to SARS-CoV-2 in Switzerland (COPEP)

Efficacy of Pragmatic Same-day Ring COVID-19 Prophylaxis for Adult Individuals Exposed to SARS-CoV-2 in Switzerland: an Open-label Cluster Randomized Trial

A study to assess, in a two-arm open-label cluster randomized clinical trial, the efficacy of a 5-day course of LPV/r treatment in preventing COVID-19 in asymptomatic individuals exposed to a SARS-CoV-2 documented index patient, compared to surveillance alone.

Study Overview

• Status: Completed
• Conditions: Prevention of COVID-19
• Intervention / Treatment: Drug: Lopinavir/ritonavir

• Study Type: Interventional
• Enrollment (Actual): 326
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Rio De Janeiro, Brazil
    • Instituto Nacional de Infectiologia Evandro Chagas, Fiocruz
• Switzerland
  • Basel, Switzerland
    • Universitätsspital Basel and SwissTPH
  • Geneva, Switzerland
    • Hopitaux Universitaires de Geneve
  • Lugano, Switzerland
    • Ospedale Regionale di Lugano

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Documented close contact with a person with either a PCR-confirmed SARS-CoV-2 or a positive rapid SARS-CoV-2 antigen test (as per standard of care).
2. Enrolment of the participant no more than 7 days since last contact with index case;
3. ≥ 16 years of age;
4. Informed consent as documented by signature (including parent's or legal guardian's signature if the participant is between 16 and 18 y.o.).

Exclusion criteria*:

1. Fever (temperature >38.0°C) and/or respiratory symptoms (cough, dyspnea) and/or new anosmia/ageusia;
2. Individuals with previous confirmed SARS-CoV-2 infection, dating within the last six months ;
3. Known impairment of liver function;
4. Known hypersensitivity to the study medications;
5. Use of any medications that are contraindicated with lopinavir/ritonavir using the website www.hiv-druginteractions.org/checker
6. Individuals on boosted protease inhibitor (other than LPV) or boosted elvitegravir as part of an antiretroviral therapy
7. Inability to be followed-up for the trial period

8. Documented vaccination against SARS-CoV-2

   • Where necessary, additional biological and clinical assessment will be performed, based on clinical judgement.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Lopinavir/Ritonavir	Drug: Lopinavir/ritonavir; 2x 200mg/50mg, twice daily for 5 days (bid, PO)
No Intervention: Active surveillance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
21-day incidence of COVID-19 in individuals exposed to SARS-CoV- 2 who are asymptomatic at baseline (intent-to-treat (ITT) analysis).	21-day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
21-day incidence of COVID-19 in individuals exposed to SARS-CoV- 2 who are asymptomatic, PCR-confirmed SARS-CoV-2 negative and have negative SARS-CoV-2 serology at baseline (modified ITT)		21-day
21-day incidence of SARS-CoV-2 infection in individuals exposed to SARS-CoV-2 who are asymptomatic, PCR-confirmed SARS-CoV-2 negative and have negative SARS-CoV-2 serology at baseline (modified ITT)		21-day
Severity of clinical COVID-19 on a 7-point ordinal scale	(1: not hospitalized, no limitations on activities, 2: not hospitalized, limitation on activities, 3: hospitalized, not requiring supplemental oxygen, 4: hospitalized, requiring supplemental oxygen, 5: hospitalized, on non- invasive mechanical ventilation 6: hospitalized, on invasive mechanical ventilation or ECMO and 7: death)	21-day

Collaborators and Investigators

• Sponsor: Calmy Alexandra
• Investigators: Principal Investigator: Alexandra Calmy, Prof, Hopitaux Universitaires de Geneve; Principal Investigator: Niklaus Labhardt, Prof, Universitatsspital Basel

Publications and helpful links

General Publications

• Labhardt ND, Smit M, Petignat I, Perneger T, Marinosci A, Ustero P, Diniz Ribeiro MP, Ragozzino S, Nicoletti GJ, Fare PB, Andrey DO, Jacquerioz F, Lebowitz D, Agoritsas T, Meyer B, Spechbach H, Salamun J, Guessous I, Chappuis F, Kaiser L, Decosterd LA, Grinsztejn B, Bernasconi E, Cardoso SW, Calmy A, Team FTCS. Post-exposure Lopinavir-Ritonavir Prophylaxis versus Surveillance for Individuals Exposed to SARS-CoV-2: The COPEP Pragmatic Open-Label, Cluster Randomized Trial. EClinicalMedicine. 2021 Dec;42:101188. doi: 10.1016/j.eclinm.2021.101188. Epub 2021 Nov 6.
• Smit M, Marinosci A, Nicoletti GJ, Perneger T, Ragozzino S, Andrey DO, Stoeckle M, Jacquerioz F, Lebowitz D, Agoritsas T, Meyer B, Spechbach H, Salamun J, Back M, Schaubhut C, Fuchs S, Decosterd L, Battegay M, Guessous I, Chappuis F, Kaiser L, Labhardt ND, Calmy A. Efficacy of pragmatic same-day ring prophylaxis for adult individuals exposed to SARS-CoV-2 in Switzerland (COPEP): protocol of an open-label cluster randomised trial. BMJ Open. 2020 Nov 12;10(11):e040110. doi: 10.1136/bmjopen-2020-040110.

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2020
• Primary Completion (Actual): March 24, 2021
• Study Completion (Actual): March 24, 2021

Study Registration Dates

• First Submitted: April 23, 2020
• First Submitted That Met QC Criteria: April 24, 2020
• First Posted (Actual): April 27, 2020

Study Record Updates

• Last Update Posted (Actual): April 12, 2021
• Last Update Submitted That Met QC Criteria: April 9, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: COVID-19
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir; Lopinavir
• Other Study ID Numbers: CCER 2020-00864

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No