Clinical trial NCT01209754: EMBRACE (Evaluation of Maternal and Baby Outcome Registry After Chemoprophylactic Exposure)
Official title: HIV Prevention Agent Pregnancy Exposure Registry: EMBRACE Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pregnancy Related
Keywords: Pregnancy
Chemoprophylactic Exposure
Mother
Infant
malformations
HIV
Lead sponsor: Microbicide Trials Network
Sponsor class: NETWORK
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2010-09-27
Enrollment: 873
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population will consist of female participants who become or became pregnant during HIV prevention agent trials, or who have or had planned exposures in pregnancy safety studies, and the infants resulting from those pregnancies. Mother participants must still be pregnant, or have had a pregnancy outcome diagnosis less than one year before screening/enrollment, and infant participants must be less than one year old. The study may include HIV-uninfected and -infected participants. Mothers may participate in EMBRACE without participation of their infants; however, infants whose mothers have not enrolled in EMBRACE will not participate.

Brief summary: The Prevention Agent Pregnancy Exposure Registry, also known as EMBRACE (Evaluation of Maternal and Baby Outcome Registry After Chemoprophylactic Exposure) is a prospective observational cohort investigation of exposures to study agents under investigation for HIV prevention. The study population will consist of female participants who are identified as becoming pregnant during their participation in a microbicide or PrEP trial, or who have had planned exposures in pregnancy safety studies as well as their babies resulting from these pregnancies. This study will only enroll babies who have not yet reached their 1 year birth date.

Detailed description: The Prevention Agent Pregnancy Exposure Registry, also known as EMBRACE (Evaluation of Maternal and Baby Outcome Registry After Chemoprophylactic Exposure) is a prospective observational cohort study of maternal exposures to investigational HIV prevention agents. Approximately 550 pregnant participants and 400 live infants will be offered enrollment. The study population will consist of current or recent female participants identified as becoming pregnant during microbicide or PrEP trials, or who have had planned exposures in pregnancy safety studies. This study will also include infants resulting from those pregnancies. This protocol will monitor for adverse pregnancy and delivery outcomes, monitor the prevalence of major malformations, evaluate growth parameters of infants during the first year of life, and evaluate the prevalence and persistence of HIV drug resistance mutations in a cohort of infants who were either exposed to active study agents or not exposed to active study agents while in utero.

Eligibility criteria: Inclusion Criteria: Mother cohort

1. Able and willing to provide written informed consent to take part in the study
2. During participation in a parent protocol, has/had a known confirmed pregnancy, meeting at least one of the following sets of criteria in A or B:

   A. Two consecutive monthly study visits, at least 14 days apart, with positive pregnancy tests, in the absence of signs/symptoms of miscarriage or participant report of pregnancy termination.

   B. One or more of the following assessments:
   * Auscultation of fetal heart tones
   * Positive pregnancy test confirmed by clinic staff in the presence of clinically confirmed enlarged uterus
   * Positive pregnancy test confirmed by clinic staff in the presence of missed menses (no menses occurring at least 60 days from the first day of the last menses) by participant report (For amenorrheic or irregularly cycling women, two consecutive positive hCG tests (criterion A) or any of the other clinical signs of pregnancy included under the criteria B listing will be used to confirm MTN-016 eligibility).
   * Clinical assessment of fetal movement
   * Demonstration of pregnancy by ultrasound
3. Able and willing to provide adequate locator information, as defined in site SOPs

Note: Participants do not have to be currently enrolled or engaged in follow-up in a parent protocol to participate in EMBRACE.

Inclusion Criteria: Infant cohort

1. Has written informed consent provided by parent(s)/guardian to take part in the study in a manner consistent with local standards, site Institutional Review Board (IRB) guidance and the US Code of Federal Regulations (CFR)
2. Born to EMBRACE participant mother from pregnancy concurrent with participation in parent study

Exclusion Criteria: Mother cohort

1. Has any condition that in the opinion of the investigator or designee, would complicate interpretation of study outcome data, make participation in the study unsafe, or otherwise interfere with achieving the study objectives
2. Pregnancy outcome occurred greater than one year ago

Exclusion Criteria: Infant cohort

1. Has any condition that, in the opinion of the investigator or designee, would complicate interpretation of study outcome data, make participation in the study unsafe, or otherwise interfere with achieving the study objectives
2. Has reached 1 year birth date

Primary outcomes:
measure: Pregnancy and delivery outcomes comparison
timeFrame: Duration of Study
measure: Major malformations comparison
timeFrame: Duration of Study
Secondary outcomes:
measure: Infant growth parameters comparison
timeFrame: Duration of Study
measure: HIV drug resistance mutations comparison
timeFrame: Duration of Study
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Johannesburg
country: South Africa
facility: Wits Reproductive Health Institute (WRHI)
state: Gauteng
city: Johannesburg
country: South Africa
facility: CAPRISA-The Aurum Institute
state: Guateng
city: Durban
country: South Africa
facility: CAPRISA eThekwini
state: KwaZulu Natal
city: Johannesburg
country: South Africa
facility: Perinatal HIV Research Unit (PHRU)
state: Soweto
city: Durban
country: South Africa
facility: South African MRC HIV CTU Med Research Council; Botha's Hill Clinical Research Site
city: Durban
country: South Africa
facility: South African MRC HIV CTU Med Research Council; Isipingo
city: Durban
country: South Africa
facility: South African MRC HIV CTU Med Research Council; Overport
city: Durban
country: South Africa
facility: South African MRC HIV CTU Med Research Council; R.K. Khan Hospital
city: Durban
country: South Africa
facility: South African MRC HIV CTU Med Research Council; Tongaat
city: Durban
country: South Africa
facility: South African MRC HIV CTU Med Research Council; Umkomaas
city: Durban
country: South Africa
facility: South African MRC HIV CTU Med Research Council; Verulam
city: Kampala
country: Uganda
facility: Makerere University-Johns Hopkins University Collaboration
city: Chitungwiza
country: Zimbabwe
facility: UZ-UCSF HIV Prevention Trials Unit
state: Seke South
city: Harare
country: Zimbabwe
facility: UZ-UCSF HIV Prevention Trials Unit
state: Spilhaus
city: Chitungwiza
country: Zimbabwe
facility: UZ-UCSF HIV Prevention Trials Unit
state: Zengeza
Study officials:
affiliation: Microbicide Trials Network
name: Richard Beigi, MD
role: STUDY_CHAIR
References:
citation: Makanani B, Balkus JE, Jiao Y, Noguchi LM, Palanee-Phillips T, Mbilizi Y, Moodley J, Kintu K, Reddy K, Kabwigu S, Jeenariain N, Harkoo I, Mgodi N, Piper J, Rees H, Scheckter R, Beigi R, Baeten JM. Pregnancy and Infant Outcomes Among Women Using the Dapivirine Vaginal Ring in Early Pregnancy. J Acquir Immune Defic Syndr. 2018 Dec 15;79(5):566-572. doi: 10.1097/QAI.0000000000001861.
citation: Mhlanga FG, Noguchi L, Balkus JE, Kabwigu S, Scheckter R, Piper J, Watts H, O'Rourke C, Torjesen K, Brown ER, Hillier SL, Beigi R. Implementation of a prospective pregnancy registry for antiretroviral based HIV prevention trials. HIV Clin Trials. 2018 Feb;19(1):8-14. doi: 10.1080/15284336.2017.1411419. Epub 2017 Dec 21.