title: 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.
abstract: BACKGROUND
  In Canada, the majority of HIV-positive pregnant women receive combination antiretroviral therapy that includes a ritonavir-boosted protease inhibitor to prevent mother-to-child HIV transmission. However, protease inhibitor-based combination antiretroviral therapy has been associated with increased rates of preterm, low birth weight, and small for gestational age births. Our previous experimental findings demonstrate that protease inhibitor use during pregnancy is associated with decreased progesterone levels that correlate with fetal growth, and that progesterone supplementation can improve protease inhibitor-induced fetal growth restriction. We hypothesize that HIV-positive pregnant women who receive protease inhibitor-based combination therapy may also benefit from progesterone supplementation during pregnancy.
  
  
  METHODS
  In order to test this hypothesis, we have designed an open-label, multi-centre, randomized controlled (parallel group) pilot trial. The initial goal of this trial is to test feasibility and acceptability of our intervention. Forty HIV-positive pregnant women who are either on, or intending to start or switch to a boosted protease inhibitor-based combination antiretroviral regimen will be enrolled from six sites across Ontario, Canada. Twenty-five women will be randomized to self-administer natural progesterone (Prometrium, 200 mg) vaginally every night starting between gestational week 16 and 24 until week 36, and 15 women will be randomized to no intervention. While the participants and treating physicians will not be blinded, the laboratory personnel performing the biochemical and morphological evaluations will be blinded to ensure unbiased evaluation. The primary outcome of the pilot study is the feasibility of enrolment as measured by the recruitment rate and patient-reported reasons to decline participation. Secondary outcomes in participants include safety, acceptability, and adherence to progesterone supplementation.
  
  
  CONCLUSIONS
  Given the safety of intravaginal progesterone and its current use in the general obstetrical population to prevent recurrent preterm delivery, this pilot study will provide data to determine the feasibility of a larger randomized controlled trial to assess the impact of this intervention on improving neonatal health in the context of HIV-positive pregnancies.
  
  
  BACKGROUND
  ClinicalTrials.gov, NCT02400021.
authors.affiliation: Toronto General Research Institute, Toronto, Canada.
authors.forename: Kaitlin
authors.initials: K
authors.lastname: Siou
authors.affiliation: Toronto General Hospital, Toronto, Canada ; University of Toronto, Toronto, Canada.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Walmsley
authors.affiliation: Mount Sinai Hospital, Toronto, Canada ; University of Toronto, Toronto, Canada.
authors.forename: Kellie E
authors.initials: KE
authors.lastname: Murphy
authors.affiliation: Toronto General Research Institute, Toronto, Canada.
authors.forename: Janet
authors.initials: J
authors.lastname: Raboud
authors.affiliation: Maple Leaf Medical Clinic, Toronto, Canada ; Women's College Research Institute, Toronto, Canada ; University of Toronto, Toronto, Canada.
authors.forename: Mona
authors.initials: M
authors.lastname: Loutfy
authors.affiliation: St. Michael's Hospital, Toronto, Canada ; University of Toronto, Toronto, Canada.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Yudin
authors.affiliation: St. Joseph's Health Care London, London, Canada ; University of Western Ontario, London, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Silverman
authors.affiliation: Sunnybrook Health Sciences Centre, Toronto, Canada ; University of Toronto, Toronto, Canada.
authors.forename: Noor N
authors.initials: NN
authors.lastname: Ladhani
authors.affiliation: Toronto General Research Institute, Toronto, Canada ; University of Toronto, Toronto, Canada ; Women's College Research Institute, Toronto, Canada.
authors.forename: Lena
authors.identifier: 0000-0002-2817-6134
authors.initials: L
authors.lastname: Serghides
keywords: Feasibility; HIV; Low birth weight; Pilot study; Pregnancy; Preterm birth; Progesterone supplementation; Protease inhibitors; RCT