A non-interventional post-authorization safety study (NI-PASS) of outcomes associated with the use of tacrolimus around conception, or during pregnancy or lactation using data from Transplant Pregnancy Registry International (TPRI)

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Name of medicine, other:
  Tacrolimus
• Study drug International non-proprietary name (INN) or common name:
  TACROLIMUS
• Anatomical Therapeutic Chemical (ATC) code:
  (L04AD02) tacrolimus

  tacrolimus

Population studied

• Short description of the study population:
  The study population consisted of transplant recipients in a defined tacrolimus-exposed group, as well as a defined alternative immunosuppressant group identified from the transplant pregnancy registry international (TPRI), from initial marketing of tacrolimus in the United States (1994) until 31 December 2020.
• Age groups:
  • Paediatric Population (< 18 years)

    • Neonate

      • Preterm newborn infants (0 – 27 days)
      • Term newborn infants (0 – 27 days)
    • Infants and toddlers (28 days – 23 months)
    • Children (2 to < 12 years)
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
• Special population of interest:
  Pregnant women
• Estimated number of subjects:
  3515

Study design details

• Main study objective:
  To estimate prevalence of major malformations (as a combined group), among livebirth children born to female transplant recipients using tacrolimus-containing-regimens (or alternative immunosuppressants, as a combined group) during the period from 6 weeks prior to conception to the end of the first trimester without use of mycophenolic acid (MPA). Similarly, for minor malformations (as a combined group).
• Outcomes:
  Newborn outcomes: major and minor malformations, small for gestational age/intrauterine growth retardation (SGA/IUGR). Pregnancy outcomes: live births, spontaneous abortions, still births. Maternal outcomes: gestational diabetes mellitus (GDM), gestational hypertension (GH), pre-eclampsia.
• Data analysis plan:
  This is a descriptive study and provides estimates together with confidence intervals for the defined outcomes in the different groups.