Progesterone Supplementation for HIV-positive Pregnant Women on Anti-Retrovirals

HIV-1 Infection Clinical Trial

— ProSPAR  

Official title:

Progesterone Supplementation for HIV-positive Pregnant Women on Anti-Retrovirals

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02400021
• Other study ID #: CTNPT025
• Status: Not yet recruiting
• Phase: Phase 2
• First received: March 23, 2015
• Last updated: July 28, 2015
• Start date: August 2015
• Est. completion date: December 2016

Study information

• Verified date: July 2015
• Source: Mount Sinai Hospital, Canada
• Contact: Lena Serghides, PhD
• Phone: 647-230-7450
• Email: lena.serghides[@]utoronto.ca
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

In pregnancy, cART is considered optimal for maternal health and for preventing the emergence of resistance that could compromise further care. In Canada, the majority of HIV-positive pregnant women receive a PI-based cART regimen. In the past, therapy was generally deferred until after the first trimester (if not required for maternal health) to minimize any unknown risk of teratogenicity. However, as treatment is now started earlier in HIV infection and as perinatal transmission rates are lowest in those with prolonged suppression of viral load during pregnancy, women are increasingly commencing cART either before conception or earlier in pregnancy.

Multiple reports and cohort studies provided data suggesting an association between PI-based cART use and preterm birth, low birth weight, and small for gestational age (SGA) babies, although conflicting data exist.

In the general population progesterone supplementation is widely used, is well tolerated, is considered safe, and is beneficial to prevent recurrent pre-term birth and increase birth weight. The investigators experimental findings suggest that PI use during pregnancy is associated with declines in progesterone levels that correlate with fetal growth, and that progesterone supplementation can improve PI-induced fetal growth restriction. The investigators preliminary findings in HIV+ pregnant women suggest that PI-use is associated with declines in progesterone levels, which correlate with birth weight percentile. Since HIV-positive women have higher rates of pre-term delivery and low birth weight that may be magnified by the use of PIs, then progesterone supplementation could be of benefit to neonatal health in the context of HIV-positive pregnancy.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Documented HIV-1 infection

• On (stable) or initiating a cART regimen containing either ritonavir-boosted lopinavir (LPV/r), atazanavir (ATZ/r) or darunavir (DRV/r)

• Pregnant up to 24 weeks gestational age

• Singleton pregnancy

• 18 years or older

• Ability to give informed consent

Exclusion Criteria:

• Hypersensitivity or allergy to soya or peanut (non-active ingredient supplement in Prometrium)

• Contraindications to intravaginal progesterone use including:

• documented hypersensitivity to Prometrium

• active or history of breast cancer,

• active or history of arterial thromboembolitic disease (e.g. stroke, myocardial infarction, coronary heart disease)

• active or history of venous thromboembolism (e.g. deep venous thrombosis or pulmonary embolism) or active thrombophlebitis

• any prior neoplasia, except for skin

• abnormal vaginal bleeding

• Known lethal fetal anomaly

• Any contraindication to continuation of pregnancy

• Inability to communicate in English

• Prior participation in this trial

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV-1 Infection

Intervention

Drug:
• Prometrium

Locations

Country	Name	City	State
Canada	St. Joseph's Hospital	London	Ontario
Canada	Maple Leaf Medical Clinic	Toronto	Ontario
Canada	Mount Sinai Hospital	Toronto	Ontario
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	Toronto General Hospital	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Mount Sinai Hospital, Canada	CIHR Canadian HIV Trials Network

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Serum progesterone levels at GW25-28 and GW33-36, described by treatment group.	SD and intra-patient correlation coefficient of trough serum progesterone levels will be calculated	28 weeks, 36 weeks	No
Other	Urine progesterone levels at GW25-28 and GW33-36, described by treatment group	SD and intra-patient correlation coefficient will be calculated.	28 weeks, 36 weeks	No
Other	Distribution of birth weight, birth weight percentile, and gestational age at birth, compared by treatment group.	ITT and on-treatment analysis	40 weeks	No
Other	Relationship between progesterone levels (serum or urine) at GW25-28 or GW33-36 and birth weight, birth weight percentile, and gestation age at birth.	assessed with spearman's rank correlation	28 weeks, 36 weeks	No
Other	Serum/urine progesterone levels compared between women with and without an AE/SAE.		40 weeks	Yes
Other	Biomarker analysis	levels of sex steroids, angiogenic, vasoactive, and inflammatory factors, factors associated with placentation, placenta dysfunction, pre-term delivery and fetal growth restriction between treatment groups	40 weeks	No
Other	Placenta morphology between treatment groups	Qualitative assessment performed blinded to the arm allocation and birth outcome	40 weeks	No
Other	Progesterone supplementation effect on PI drug levels	trough PI drug levels in plasma collected from women in both tx groups at baseline and each study visit. changes in drug levels over time will be evaluated.	40 weeks	No
Primary	Total enrollment / eligible population per year	Qualitative information on the reasons to decline participation will be collected and summarized. Reasons for non-enrolling questionnaire will be used.	12 months	No
Secondary	Safety of progesterone supplementation during pregnancy for HIV-positive women.	The number of Grade 3 or 4 AE in the ITT vs. comparator group. The number of Grade 1 or 2 AE in the ITT vs. comparator group. AE questionnaire.	40 weeks	Yes
Secondary	Acceptability of progesterone supplementation during pregnancy for HIV+ women.	Assessed in the ITT group. Acceptability based on experience with medication questionnaire. Screening questionnaire (acceptability of being recruited to no treatment arm)	40 weeks	No
Secondary	Compliance of progesterone supplementation. Assessed in the ITT group.	Number of missed doses / total prescribed doses per patient. Compliance questionnaire	40 weeks	No
Secondary	Barriers to adherence to progesterone supplementation. Assessed in the ITT group	Reasons for missed dose questionnaire. Reasons for missed appointment questionnaire	40 weeks	No