Premature Obstetric LaborPhase 1PROGRAMNCT03152942
Progesterone and Aminophylline for the Prevention of Preterm Labour
A Phase 1 study testing Progesterone and Aminophylline in people with Premature Obstetric Labor, run by St Stephens Aids Trust at 1 site in United Kingdom.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Premature Obstetric Labor
- What is being tested?
- Progesterone and Aminophylline
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 5 Oct 2017to Apr 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Chelsea and Westminster Hospital
London, SW10 9TH
Mark Johnson, +44 (0) 203 315 7892, mark.johnson@imperial.ac.uk
Natasha Singh
About this study
Official title: A Randomised Controlled Feasibility Study of the Tolerability of the Combination of Progesterone and Aminophylline for the Prevention of Preterm Labour
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.
Read the detailed description
Name of Investigational Product: Cyclogest® 400 mg, Phyllocontin® Continus®
Name of active ingredients:Progesterone PhEur 400 mg, Aminophylline hydrate 225 mg
Phase of study: Phase I
Primary Objectives:
- To assess how many 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.
Secondary Objectives:
- The effect on the maternal immune system.
- The impact on preterm delivery and episodes of threatened PTL.
- The number of women who deliver before 34 weeks.
Methodology:
This randomised controlled feasibility study will establish the viability of conducting a multicentre randomised controlled study to definitively test the effects of the combination of Progesterone (P4) and aminophylline against P4 alone.
Participants (n=70) will be randomised into one of two groups. One group will receive P4 alone while the second group will receive a combination of P4 and aminophylline. Following randomisation to P4 alone or in combination with aminophylline, participants will be given a prescription to be taken to the pharmacy.
All participants will be given a prescription for P4 400 mg to be inserted into the vagina at bedtime until 34 weeks.
Participants randomised to the combined arm will also be given a prescription for aminophylline 225 mg to be taken once at night for 1 week and then if tolerated increased to 225 mg twice daily.
Subjects will attend the unit for 34 weeks for clinical review and safety monitoring. Treatment will be continued until 34 weeks of gestation or until preterm delivery (whichever occurs first).
During the safety visits, flow cytometry will be used to determine inflammatory cell numbers and their activation status in cervical and blood samples.
Cervico-vaginal fluid and peripheral blood plasma will also be stored at - 80oC until multiplex analysis of cytokine and chemokine content.
Summary of eligibility criteria:
- Obstetric history: previous mid-trimester loss and preterm delivery
- 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
Primary Endpoint:
- The number of women maintained on the combination therapy P4 and aminophylline arm and the P4 alone alrm up to 34 weeks of treatment. A positive outcome would be seeing 80% or more women maintained on therapy.
Secondary Endpoint:
- The effects on the maternal immune system.
- The number of women who deliver before the end of the study (34 weeks).
- The impact on preterm delivery and episodes of threatened PTL.
- Conditions
- Premature Obstetric Labor
- Being tested
- Progesterone, Aminophylline
- Medical subject headings
- Obstetric Labor, Premature
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ProgesteroneDrug
Also called Cyclogest
Progesterone 400mg to be administered once daily for 34 weeks in the patients randomised to receive progesterone alone
AminophyllineDrug
Also called Phyllocontin® Continus®
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.
| Study group | Role | What they receive |
|---|---|---|
| Progesterone alone | Experimental | Progesterone 400 mg once daily until 34 weeks. Receives: Drug: Progesterone |
| Progesterone and aminophylline. | Active comparator | Progesterone 400 mg and aminophylline 225 mg once daily until 34 weeks. Receives: Drug: Progesterone; Drug: Aminophylline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 34 weeks
Secondary outcomes (3)
To assess the effect on the maternal immune system.
By studying cervicovaginal swabs taken every 4 weeks, blood tests, and measuring levels of cytokine and chemokine inflammatory profile.
Measured: 34 weeks
The impact on preterm delivery and episodes of threatened Preterm Labour
This will be measured by number of preterm deliveries and reported side effects between the two groups on combination and mono therapy.
Measured: 34 weeks
The number of women who deliver before 34 weeks.
Measuring the number of patients who deliver before 34 weeks.
Measured: 34 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2017
- Study start5 Oct 2017
- Primary completionOct 2018 (estimated)
- Study completionApr 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Premature Obstetric LaborStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- St Stephens Aids Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Action Medical Research
- Responsible party
- Sponsor
- Investigators
- Mark Johnson, Professor, Principal investigator, Chelsea and Westminster Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03152942
- Sponsor's protocol ID
- SSAT068
- Acronym
- PROGRAM
- Status last verified
- Oct 2017
- First submitted
- 3 Jul 2016
- Last updated
- 28 Feb 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 40148792
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Controlled Feasibility Study of the Tolerability of the Combination of Progesterone and Aminophylline for the Prevention of Preterm Labour
- ClinicalTrials.gov ID
- NCT03152942
- Acronym / sponsor ID
- PROGRAM / SSAT068
- Conditions
- Premature Obstetric Labor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- St Stephens Aids TrustUniversity, hospital or other
- Collaborators
- Action Medical Research
- Study start
- 5 Oct 2017 (actual)
- Primary completion
- Oct 2018 (estimated)
- Study completion
- Apr 2019 (estimated)
- First posted
- 15 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Name of Investigational Product: Cyclogest® 400 mg, Phyllocontin® Continus®
Name of active ingredients:Progesterone PhEur 400 mg, Aminophylline hydrate 225 mg
Phase of study: Phase I
Primary Objectives:
- To assess how many 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.
Secondary Objectives:
- The effect on the maternal immune system.
- The impact on preterm delivery and episodes of threatened PTL.
- The number of women who deliver before 34 weeks.
Methodology:
This randomised controlled feasibility study will establish the viability of conducting a multicentre randomised controlled study to definitively test the effects of the combination of Progesterone (P4) and aminophylline against P4 alone.
Participants (n=70) will be randomised into one of two groups. One group will receive P4 alone while the second group will receive a combination of P4 and aminophylline. Following randomisation to P4 alone or in combination with aminophylline, participants will be given a prescription to be taken to the pharmacy.
All participants will be given a prescription for P4 400 mg to be inserted into the vagina at bedtime until 34 weeks.
Participants randomised to the combined arm will also be given a prescription for aminophylline 225 mg to be taken once at night for 1 week and then if tolerated increased to 225 mg twice daily.
Subjects will attend the unit for 34 weeks for clinical review and safety monitoring. Treatment will be continued until 34 weeks of gestation or until preterm delivery (whichever occurs first).
During the safety visits, flow cytometry will be used to determine inflammatory cell numbers and their activation status in cervical and blood samples.
Cervico-vaginal fluid and peripheral blood plasma will also be stored at - 80oC until multiplex analysis of cytokine and chemokine content.
Summary of eligibility criteria:
- Obstetric history: previous mid-trimester loss and preterm delivery
- 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
Primary Endpoint:
- The number of women maintained on the combination therapy P4 and aminophylline arm and the P4 alone alrm up to 34 weeks of treatment. A positive outcome would be seeing 80% or more women maintained on therapy.
Secondary Endpoint:
- The effects on the maternal immune system.
- The number of women who deliver before the end of the study (34 weeks).
- The impact on preterm delivery and episodes of threatened PTL.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Progesterone alone | Experimental | Drug: ProgesteroneProgesterone 400 mg once daily until 34 weeks. |
| Progesterone and aminophylline. | Active comparator | Drug: Progesterone, Drug: AminophyllineProgesterone 400 mg and aminophylline 225 mg once daily until 34 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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).
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ProgesteroneAlso: CyclogestProgesterone 400mg to be administered once daily for 34 weeks in the patients randomised to receive progesterone alone | Drug | Progesterone alone, Progesterone and aminophylline. |
| AminophyllineAlso: Phyllocontin® Continus®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. | Drug | Progesterone and aminophylline. |
Primary outcome
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.
Time frame: 34 weeks
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).
3 secondary outcomes
To assess the effect on the maternal immune system.
Time frame: 34 weeks
The impact on preterm delivery and episodes of threatened Preterm Labour
Time frame: 34 weeks
The number of women who deliver before 34 weeks.
Time frame: 34 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2018.
- Derived from this study: PubMed 40148792Singh 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Johnson, Professor principal investigator
Chelsea and Westminster Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Progesterone and Aminophylline in people with Premature Obstetric Labor, run by St Stephens Aids Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Project Manager Mailbox (+44 (0) 203 828 0569, SSAT068@ststcr.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: 34 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03152942, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2018.