Clinical trial NCT05894603: Effectiveness and Safety of New Oral Antivirals for COVID-19
Official title: Post-marketing Surveillance Study of the Effectiveness and Safety of New Oral Antivirals for Outpatients With Mild-moderate COVID-19
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: COVID-19
Keywords: Post-marketing surveillance
COVID-19
Antivirals
Effectiveness
Safety
Lead sponsor: Universidade do Porto
Sponsor class: OTHER
Collaborators: name: Centro de Investigação em Tecnologias e Serviços de Saúde
name: Rede de Investigação em Saúde
First posted: 2023-06-08
Enrollment: 211
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients receiving the oral antivirals against COVID-19 - Paxlovid® or Lagevrio®.

Brief summary: There is an increased lack of short- and long-term real-life effectiveness and safety data on new oral antivirals authorised and commercialised to treat COVID-19. To date, only two clinical trials have been published with data on the efficacy and safety of the use of the Paxlovid® and Lagevrio®. Since there is a public health, political, social and economic pressure to prevent severity, hospitalisation and death from COVID-19, monitoring the effectiveness and safety of commercialised oral antiviral therapies against COVID-19 has become emergent pharmacovigilance and public health task. The objective of the study is to monitor the post-marketing safety and effectiveness of the new oral antivirals indicated for the treatment of COVID-19, namely Nirmatrelvir/Ritonavir (Paxlovid®) and Molnupiravir (Lagevrio®), having as holders of the Authorization of Market introduction to Pfizer Europe MA EEIG and Merck Sharp \& Dohme B.V., respectively.

Detailed description: There is an increased lack of short- and long-term real-life effectiveness and safety data on new oral antivirals authorised and commercialised to treat COVID-19. To date, only two clinical trials have been published with data on the efficacy and safety of the use of the Paxlovid® and Lagevrio®. Since there is a public health, political, social and economic pressure to prevent severity, hospitalisation and death from COVID-19, monitoring the effectiveness and safety of commercialised oral antiviral therapies against COVID-19 has become emergent pharmacovigilance and public health task6.

A real-life cohort event monitoring system allows for the monitoring of newly introduced oral antivirals, in addition to existing spontaneous reporting systems and healthcare database studies (i.e., secondary data), as it is complementary to these systems in several ways. First, it is better suited to capture the more frequent AE, including those that are not medically attended. It generates more comprehensive safety data, e.g. on disease course and the impact of the AE. Moreover, there is insufficient data on these new medicines in real clinical practice, particularly from large-scale studies on the long-term efficacy or safety.

This work, with scientific and academic interest but, essentially, clinical and regulatory importance, constitutes a duty of the regional pharmacovigilance units. As such, it is also an obligation of the Pharmacy and Therapeutics Commissions, based on the legislation in force, to "collaborate in studies to monitor the safety and effectiveness of medicines promoted in the context of the National Pharmacovigilance System".

Eligibility criteria: Inclusion Criteria:

Participants eligible to be included in the study are identified by medical prescribing of one of the drugs under study, and either the medicine recipient or their proxy should:

1. Comply with the eligibility criteria for prescribing these drugs (including patients ≥ 18 years old), according to Norm nr 005/2022 of the General Directorate of Health of Portugal\*;
2. Enrol in the study within the first 72 hours after dispensing treatment;
3. Be able to understand the Portuguese language;
4. Available for follow-up during study time;
5. Provide informed consent.

   * Compliance with the eligibility criteria for prescribing these drugs is the sole responsibility of the prescriber who assesses the patient, so the study centres only include patients referred by the prescriber.

Exclusion Criteria:

Will be considered ineligible participants those who:

1. Are not available for follow-up and monitoring;
2. Participate in phase I, II, III or IV clinical trials;
3. Life expectancy is less than one month.

Primary outcomes:
measure: Safety outcome
timeFrame: 6 days after onset treatment for both drugs.
measure: Safety outcome
timeFrame: 39 days after treatment onset for nirmatrelvir/ritonavir cohort.
measure: Safety outcome
timeFrame: 19 days after treatment onset for molnupiravir cohort.
measure: Effectiveness outcome
timeFrame: 29 days after treatment onset for both drugs.
Secondary outcomes:
measure: Adherence to treatment
timeFrame: 6 days after onset treatment for both drugs.
Other outcomes:
Locations:
city: Açores
country: Portugal
facility: Hospital do Divino Espírito Santo de Ponta Delgada, EPE
city: Lisboa
country: Portugal
facility: Centro Hospitalar de Lisboa Ocidental, EPE
city: Porto
country: Portugal
facility: Centro Hospitalar de Vila Nova de Gaia/Espinho, EPE
city: Porto
country: Portugal
facility: Centro Hospitalar e Universitário de São João, EPE
city: Porto
country: Portugal
facility: Centro Hospitalar Universitário de Santo António, EPE
city: Porto
country: Portugal
facility: Unidade de Saúde Familiar - Homem do Leme (ACES Porto Ocidental)
Study officials:
affiliation: Universidade do Porto
name: Jorge Junqueira Polónia, MD, PhD
role: STUDY_DIRECTOR
References: