Post-marketing Surveillance Study of the Effectiveness and Safety of new Oral Antivirals for outpatients with mild-moderate COVID-19. (ESOA-19)

Study type

• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Drug utilisation

  Effectiveness study (incl. comparative)

Non-interventional study

• Non-interventional study design:
  Cohort

  Other
• Non-interventional study design, other:
  Prescription event monitoring

Study drug and medical condition

• Name of medicine:
  PAXLOVID

  LAGEVRIO
• Study drug International non-proprietary name (INN) or common name:
  NIRMATRELVIR

  RITONAVIR
• Anatomical Therapeutic Chemical (ATC) code:
  (J05AE30) nirmatrelvir and ritonavir

  nirmatrelvir and ritonavir
• Medical condition to be studied:
  COVID-19

Population studied

• Age groups:
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)
• Special population of interest:
  Hepatic impaired

  Immunocompromised

  Renal impaired
• Estimated number of subjects:
  107

Study design details

• Main study objective:
  To generate real-world evidence on the effectiveness and safety of COVID-19 oral antiviral medicines, therefore contributing to support informed political, regulatory and clinical decisions.
• Outcomes:
  Safety outcomes: the incidence of AE (with particular focus on AE of special interest) that emerge during or after the treatment period, serious AE, and AE leading to discontinuation of the treatment, as coded according to the MedDRA. ; Effectiveness outcomes: the incidence of hospitalisation for any cause (defined as ≥24 hours of acute care in a hospital or any similar facility) or death for any, Adherence to treatment: will be measured using the self-reported 7-item Measure Treatment Adherence (MTA) tool validated for the Portuguese Population9. ; The MTA is a psychometric tool derived from the Morisky et al. questionnaire and evaluates the individuals` behavior concerning the daily use of medication.
• Data analysis plan:
  A descriptive analysis will be conducted on all study variables. ; Categorical variables will be described through absolute and relative frequencies, and continuous variables will be described by descriptive statistics using mean and standard deviation, quartiles, median value, and minimum and maximum values. ; Demographic and screening data will be described using the descriptive measures defined above and according to each variable type. Clinical information recorded at baseline visit will also be described to all subjects Univariate and multivariate regression analyses will be performed to evaluate the relationship between the presence of risk factors and AE. ; Survival analysis will be conducted for time until hospitalization and until dead (total and medicines related) and until AE. A propensity score model will be applied to compare the safety and effectiveness of the different oral antivirals.
• Summary results:
  Molnupiravir cohort: By day 29 post-treatment initiation, no deaths were reported (n = 0; 0%; 95%CI = [0,26]), and all patients were either at home or institutionalised, with favourable outcomes. ; Out of the 12 patients enrolled, eight (67%; 95%CI = [35,90]) reported at least one AE, with the median time to the first AE being five days (range 5–7 days). ; Half of the patients (n = 6; 95%CI = [21,79]) reported AE deemed possibly or probably related to molnupiravir, involving nausea (25%), dizziness (17%), bitter taste (17%), and headache (17%). ; These AE were more commonly observed in older individuals and those overweight, indicating a potential influence of these factors on AE occurrence. Molnupiravir appears to show good safety and effectiveness, offering an alternative for high-risk COVID-19 outpatients ineligible for first-line therapy. ; Despite its market withdrawal, ongoing research into its long-term effects is crucial to potentially repurpose it for other viral infections.