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

NCT02400021 | Unknown Phase 2 DMC

• 1 other identifier: CTNPT025
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 5

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.

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (4)

• Safety of progesterone supplementation during pregnancy for HIV-positive women.

  40 weeks

• Acceptability of progesterone supplementation during pregnancy for HIV+ women.

  40 weeks

• Compliance of progesterone supplementation. Assessed in the ITT group.

  40 weeks

• Barriers to adherence to progesterone supplementation. Assessed in the ITT group

  40 weeks

Other Outcomes (8)

• Serum progesterone levels at GW25-28 and GW33-36, described by treatment group.

  28 weeks, 36 weeks

• Urine progesterone levels at GW25-28 and GW33-36, described by treatment group

  28 weeks, 36 weeks

• Distribution of birth weight, birth weight percentile, and gestational age at birth, compared by treatment group.

  40 weeks

Study Arms (2)

Prometrium

EXPERIMENTAL

Prometrium (progesterone capsules) intervention

Drug: Prometrium

No treatment

NO INTERVENTION

no treatment arm

Interventions

Prometrium DRUG

Also known as: progesterone capsules

Prometrium

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• years or older
• Ability to give informed consent

You may not qualify if:

• 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

Sponsors & Collaborators

• Mount Sinai Hospital, Canada: lead
• CIHR Canadian HIV Trials Network: collaborator

Study Sites (5)

St. Joseph's Hospital

London, Ontario, N6A 4V2, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5C 2T2, Canada

Location

Maple Leaf Medical Clinic

Toronto, Ontario, M5G 1K2, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, M5G 1Z5, Canada

Location

Toronto General Hospital

Toronto, Ontario, M5G 2N2, Canada

Location

Related Publications (1)

• 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.

  PMID: 27965866 DERIVED

MeSH Terms

Interventions

Progesterone

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Corpus Luteum Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones

Study Officials

• Sharon Walmsley, MD

  Toronto General Research Institute, UHN

  PRINCIPAL INVESTIGATOR

• Kellie Murphy, MD

  Mount Sinai Hospital, Canada

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lena Serghides, PhD

CONTACT

647-230-7450; lena.serghides@utoronto.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2015
• First Posted: March 26, 2015
• Study Start: August 1, 2015
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: July 30, 2015

Record last verified: 2015-07

Locations

CA (5)