Clinical trial NCT04825782: MiMBa Pregnancy Registry
Official title: A Pregnancy Registry to Assess the Safety of Antimalarial Use in Pregnancy
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Malaria in Pregnancy
Pregnancy Related
Congenital Anomaly
Keywords: Malaria
Pharmacovigilance
Pregnancy registry
Antimalarials
Lead sponsor: Liverpool School of Tropical Medicine
Sponsor class: OTHER
Collaborators: name: Medicines for Malaria Venture
name: Worldwide Antimalarial Resistance Network
name: Kenya Medical Research Institute
First posted: 2021-04-01
Enrollment: 15000
Sex: FEMALE
Minimum age (years): 15
Maximum age (years): 49
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Women of childbearing age (40,000 to 60,000) and Pregnant Women - approximately 3000 to 5500 per year

Brief summary: The MiMBa (Malaria in Mothers and Babies) Pregnancy Registry aims to generate robust evidence on the safety of a range of antimalarials when used in pregnancy, particularly in the first trimester. This will be a multi-country observational study and will be deployed in several field sites in Africa.

Detailed description: Background:There is often no, or limited, safety data on drug use in early pregnancy and particularly for drugs targeting tropical diseases because these are not widely used in resource-rich countries with robust pharmacovigilance systems. It is critical to develop surveillance systems to assess the safety of these drugs in pregnancy. Malaria in pregnancy requires prompt and effective treatment to prevent adverse health consequences for the mother and her unborn baby. Malaria infection in the first trimester has been associated with miscarriage, preterm birth and low birth weight. Pregnant women in the first trimester are often inadvertently treated with the same antimalarials as provided to the adult population which is a concern for drugs which are contraindicated in early pregnancy, such as artemisinin combination therapies (ACTs). This occurs either because they are not aware or do not report that they are pregnant, or because quinine, the standard of care for malaria treatment in the first trimester is not available. There is limited data available about the safety of ACTs in early pregnancy. Investigators will develop a pregnancy registry for monitoring the safety of antimalarial drugs during pregnancy with a focus on the first trimester.

Overall Aim: The aim of the pregnancy registry is to generate robust data on the safety of a range of antimalarials in pregnancy and particularly use in the first trimester to inform regulators and policymakers.

Methods in Brief: Investigators will set-up a pregnancy exposure registry for antimalarial drugs to capture safety data from women inadvertently exposed to (i.e. treated with) antimalarials used in the general population that are not currently recommended for use in the first trimester. To capture this safety data, several sentinel sites will be set-up in multiple malaria-endemic countries to follow women from the moment the pregnancy is identified and capture pregnancy outcomes (i.e. miscarriage, stillbirth, live birth). Some sites (including Kenya) will provide pregnancy tests to enable early pregnancy detection and referral to ANC to capture early miscarriages. Newborns will be assessed for congenital anomalies at birth and up to 2 years of age. Any suspected case of congenital anomalies will be referred for further assessment by a specialist (e.g. paediatrician) who will confirm the diagnosis and advise on how to further manage any problems or complications. The national referral system will be used in cases requiring further intervention. Exposure data will be collected on any acute illnesses occurring during pregnancy, such as malaria and COVID-19, and chronic conditions, such as HIV, TB, epilepsy or diabetes, and details of any treatment given (including antimalarials). Antimalarial and other drug exposure data in early pregnancy, i.e. before the pregnancy was known, will be captured through record linkage with treatment records from outpatient departments, community health workers, and any other treatment records. Women will provide informed consent for this data to be collected and to be followed up throughout pregnancy. The pregnancy outcomes and prevalence of congenital anomalies will then be compared between pregnancies exposed and those not exposed to specific antimalarials during the first trimester.

Expected Outcomes: The expected outcome of this study is information and reassurance about the safety profile of specific antimalarials, with a focus on the first trimester, to inform malaria treatment guidelines. The findings will be shared with the relevant local and national health and regulatory authorities and disseminated in scientific meetings and in peer-reviewed journals. Data generated will be pooled with data from similar pregnancy registries in other malaria-endemic countries and will be shared with the WHO/TDR Central registry for epidemiological surveillance of drug safety in pregnancy and other relevant pregnancy exposure registries.

Eligibility criteria: Inclusion Criteria:

* Pregnant or women of childbearing age (15-49 years)

  * Resident within the defined catchment area. Residency status will be defined as having resided in the area for at least four months.
  * Willingness to attend antenatal care and deliver in the study area.
  * Willingness to give informed consent (and assent for non-pregnant WOCBAs under 18 years of age).

Exclusion Criteria:

* Refusal to participate or be followed up to the end of pregnancy. • Any medical, psychiatric, or social condition that would interfere with the ability to provide an accurate medical or drug history or the volunteer's ability to give informed consent (e.g. mentally disabled patients).

Primary outcomes:
measure: Miscarriage
timeFrame: Between pregnancy identification and 28 weeks gestation
measure: Stillbirth
timeFrame: Between pregnancy identification and delivery
measure: Major congenital anomalies
timeFrame: Up to 12 months after birth
Secondary outcomes:
measure: Maternal Mortality
timeFrame: Up to 6 weeks post-delivery
measure: Neonatal mortality
timeFrame: By 28 days post-delivery
measure: Low birthweight
timeFrame: Within 48 hours of birth
measure: Prematurity
timeFrame: At delivery
Other outcomes:
Locations:
city: Kisumu
country: Kenya
facility: Kenya Medical Research Institute
Study officials:
affiliation: Liverpool School of Tropical Medicine
name: Feiko ter Kuile, MD, PhD
role: STUDY_DIRECTOR
References: