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

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

Status
UNKNOWN
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02400021
Acronym
ProSPAR
Enrollment
40
Registered
2015-03-26
Start date
2015-08-31
Completion date
2016-12-31
Last updated
2015-07-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

HIV-1 Infection

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.

Interventions

Sponsors

CIHR Canadian HIV Trials Network
CollaboratorNETWORK
Mount Sinai Hospital, Canada
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)

Eligibility

Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
Total enrollment / eligible population per year12 monthsQualitative information on the reasons to decline participation will be collected and summarized. Reasons for non-enrolling questionnaire will be used.

Secondary

MeasureTime frameDescription
Safety of progesterone supplementation during pregnancy for HIV-positive women.40 weeksThe 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.
Acceptability of progesterone supplementation during pregnancy for HIV+ women.40 weeksAssessed in the ITT group. Acceptability based on experience with medication questionnaire. Screening questionnaire (acceptability of being recruited to no treatment arm)
Compliance of progesterone supplementation. Assessed in the ITT group.40 weeksNumber of missed doses / total prescribed doses per patient. Compliance questionnaire
Barriers to adherence to progesterone supplementation. Assessed in the ITT group40 weeksReasons for missed dose questionnaire. Reasons for missed appointment questionnaire

Other

MeasureTime frameDescription
Biomarker analysis40 weekslevels of sex steroids, angiogenic, vasoactive, and inflammatory factors, factors associated with placentation, placenta dysfunction, pre-term delivery and fetal growth restriction between treatment groups
Serum progesterone levels at GW25-28 and GW33-36, described by treatment group.28 weeks, 36 weeksSD and intra-patient correlation coefficient of trough serum progesterone levels will be calculated
Progesterone supplementation effect on PI drug levels40 weekstrough 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.
Placenta morphology between treatment groups40 weeksQualitative assessment performed blinded to the arm allocation and birth outcome
Urine progesterone levels at GW25-28 and GW33-36, described by treatment group28 weeks, 36 weeksSD and intra-patient correlation coefficient will be calculated.
Distribution of birth weight, birth weight percentile, and gestational age at birth, compared by treatment group.40 weeksITT and on-treatment analysis
Relationship between progesterone levels (serum or urine) at GW25-28 or GW33-36 and birth weight, birth weight percentile, and gestation age at birth.28 weeks, 36 weeksassessed with spearman's rank correlation
Serum/urine progesterone levels compared between women with and without an AE/SAE.40 weeks

Countries

Canada

Contacts

Primary ContactLena Serghides, PhD
lena.serghides@utoronto.ca647-230-7450

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Mar 12, 2026