Clinical trial NCT02400021: Progesterone Supplementation for HIV-positive Pregnant Women on Anti-Retrovirals
Official title: Progesterone Supplementation for HIV-positive Pregnant Women on Anti-Retrovirals
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: HIV-1 Infection
Lead sponsor: Mount Sinai Hospital, Canada
Sponsor class: OTHER
Collaborators: name: CIHR Canadian HIV Trials Network
First posted: 2015-03-26
Enrollment: 40
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Total enrollment / eligible population per year
timeFrame: 12 months
Secondary outcomes:
measure: Safety of progesterone supplementation during pregnancy for HIV-positive women.
timeFrame: 40 weeks
measure: Acceptability of progesterone supplementation during pregnancy for HIV+ women.
timeFrame: 40 weeks
measure: Compliance of progesterone supplementation. Assessed in the ITT group.
timeFrame: 40 weeks
measure: Barriers to adherence to progesterone supplementation. Assessed in the ITT group
timeFrame: 40 weeks
Other outcomes:
measure: Serum progesterone levels at GW25-28 and GW33-36, described by treatment group.
timeFrame: 28 weeks, 36 weeks
measure: Urine progesterone levels at GW25-28 and GW33-36, described by treatment group
timeFrame: 28 weeks, 36 weeks
measure: Distribution of birth weight, birth weight percentile, and gestational age at birth, compared by treatment group.
timeFrame: 40 weeks
measure: Relationship between progesterone levels (serum or urine) at GW25-28 or GW33-36 and birth weight, birth weight percentile, and gestation age at birth.
timeFrame: 28 weeks, 36 weeks
measure: Serum/urine progesterone levels compared between women with and without an AE/SAE.
timeFrame: 40 weeks
measure: Biomarker analysis
timeFrame: 40 weeks
measure: Placenta morphology between treatment groups
timeFrame: 40 weeks
measure: Progesterone supplementation effect on PI drug levels
timeFrame: 40 weeks
Locations:
city: London
country: Canada
facility: St. Joseph's Hospital
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Maple Leaf Medical Clinic
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
Study officials:
affiliation: Toronto General Research Institute, UHN
name: Sharon Walmsley, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mount Sinai Hospital, Canada
name: Kellie Murphy, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Siou K, Walmsley SL, Murphy KE, Raboud J, Loutfy M, Yudin MH, Silverman M, Ladhani NN, Serghides L. Progesterone supplementation for HIV-positive pregnant women on protease inhibitor-based antiretroviral regimens (the ProSPAR study): a study protocol for a pilot randomized controlled trial. Pilot Feasibility Stud. 2016 Aug 12;2:49. doi: 10.1186/s40814-016-0087-6. eCollection 2016.