Progesterone and Aminophylline for the Prevention of Preterm Labour

NCT03152942 | Unknown Phase 1

• 1 other identifier: SSAT068
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to investigate whether the combination of aminophylline and Progesterone (P4) is acceptable to women at high-risk of Pre-term labour (PTL). If this proves to be the case, a larger double blind, randomised controlled trial will be conducted to test the hypothesis that the combination of P4 and aminophylline reduces the risk of PTL more effectively than P4 alone. The study is a randomised study where participants will be either administered a combination of aminophylline and Progesterone (P4) or Progesterone (P4) alone.As the study is open label, the participants and the study doctor will know which study medications the participant is taking at all times during the study.

Conditions

Premature Obstetric Labor

Outcome Measures

Primary Outcomes (1)

• To assess number of women at high risk of Preterm Labour (PTL) withdraw from the combination therapy of Progesterone (P4) and aminophylline due to side effects, in comparison to P4 alone.

  Tolerability will be assessed by the number of participants who withdraw from the study due to severe adverse side effects at each safety visit (14, 16, 18, 22, 26, 30 and 34 weeks of pregnancy).

  34 weeks

Secondary Outcomes (3)

• To assess the effect on the maternal immune system.

  34 weeks

• The impact on preterm delivery and episodes of threatened Preterm Labour

  34 weeks

• The number of women who deliver before 34 weeks.

  34 weeks

Study Arms (2)

Progesterone alone

EXPERIMENTAL

Progesterone 400 mg once daily until 34 weeks.

Drug: Progesterone

Progesterone and aminophylline.

ACTIVE COMPARATOR

Progesterone 400 mg and aminophylline 225 mg once daily until 34 weeks.

Drug: Progesterone; Drug: Aminophylline

Interventions

Progesterone DRUG

Progesterone 400mg to be administered once daily for 34 weeks in the patients randomised to receive progesterone alone

Also known as: Cyclogest

Progesterone alone; Progesterone and aminophylline.

Aminophylline DRUG

Patients randomised to the combination arm to be administered aminophylline 225 mg to be taken once at night for 1 week and then if tolerated increased to 225 mg twice daily Progesterone 400mg to be administered once daily for 34 weeks.

Also known as: Phyllocontin® Continus®

Progesterone and aminophylline.

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pregnant women between 13 and 20 weeks of gestation.
• Singleton pregnancy.
• Intact fetal membranes at the time of recruitment.
• The ability to understand and sign a written informed consent form, prior to participation in any screening procedures and must be willing to comply with all study requirements.
• Obstetric history: previous mid-trimester loss (14 - 26 weeks) and preterm delivery (\< 37 weeks).
• Women with a history of indicated cervical suture.
• Short cervical length (≤ 25 mm) on ultrasound at 13-20+0 weeks gestation, with or without a cervical suture and with or without a positive fetal fibronectin.
• Women must be aged 18 years or older.

You may not qualify if:

• Known sensitivity, contraindication or intolerance to P4 (History of liver tumours, severe liver impairment, genital or breast cancer, severe arterial disease, undiagnosed vaginal bleeding, acute porphyria, history during pregnancy of idiopathic jaundice, severe pruritus or pemphigoid gestations)
• Known sensitivity, contraindication or intolerance to aminophylline (hypokalaemia, pre-existing cardiac arrhythmias, epilepsy, hyperparathyroidism, peptic ulcer disease)
• Suspected or proven rupture of the fetal membranes at the time of recruitment.
• Prescription or ingestion of medications known to interact with P4 (e.g Bromocriptine, carbamazepine, diazepam, lorazepam and temazepam, insulin).
• Aminophylline plasma concentrations can be increased in the presence of: acyclovir, calcium channel blockers, cimetidine, erythromycin, clarithromycin, corticosteroids and benzodiazepine, carbamazepine, beta-sympathomimetics.
• Evidence of maternal infection or sepsis (maternal temperature ≥37.5C, increased inflammatory markers - WBC, CRP).
• Multiple pregnancy.
• Known significant congenital structural or chromosomal fetal anomaly.
• Maternal pathologies in which preterm termination of pregnancy is required.
• Pre-eclampsia or severe hypertension.

Sponsors & Collaborators

• St Stephens Aids Trust: lead
• Action Medical Research: collaborator

Study Sites (1)

Chelsea and Westminster Hospital

London, SW10 9TH, United Kingdom

RECRUITING

Related Publications (1)

• Singh N, Shah NM, Sooranna G, Bourke M, Yulia A, Battersby C, Tribe RM, Johnson MR. A randomised feasibility tolerability study of aminophylline for the prevention of preterm labour. BMC Pregnancy Childbirth. 2025 Mar 27;25(1):357. doi: 10.1186/s12884-025-07488-1.

  PMID: 40148792 DERIVED

MeSH Terms

Conditions

Obstetric Labor, Premature

Interventions

Progesterone; Aminophylline

Condition Hierarchy (Ancestors)

Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

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; Ethylenediamines; Diamines; Polyamines; Amines; Organic Chemicals; Theophylline; Xanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Mark Johnson, Professor

  Chelsea and Westminster Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Project Manager Mailbox

CONTACT

+44 (0) 203 828 0569; SSAT068@ststcr.com

Marita Marshall

CONTACT

+44 (0) 7825 429 337; marita.marshall@ststcr.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2016
• First Posted: May 15, 2017
• Study Start: October 5, 2017
• Primary Completion: October 1, 2018
• Study Completion: April 1, 2019
• Last Updated: February 28, 2018

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)