Clinical trial NCT06975943: Comparison in Cervical Length and Prolongation of Gestation Age on Vaginal Progesterone Administration to Pregnant Women After the Acute Phase of Threatened Preterm Birth
Official title: Comparison in Cervical Length and Prolongation of Gestation Age on Vaginal Progesterone Administration to Pregnant Women After the Acute Phase of Threatened Preterm Birth : A Randomised Clinical Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Pregnant Women
Pregnancies at Increased Risk of Preterm Birth
Keywords: Interventional
Pregnant Women
Preterm Birth
Vaginal Progesterone
Indonesia
Lead sponsor: Dr. Soetomo General Hospital
Sponsor class: OTHER_GOV
First posted: 2025-05-16
Enrollment: 48
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This randomised clinical trial aims to investigate the effect of daily vaginal progesterone supplementation on pregnancy prolongation and cervical length changes following arrested preterm labor in singleton pregnancies. The study will recruit pregnant women between 28 and 33 weeks of gestational age who had experienced threatened preterm labor at Dr. Soetomo Hospital in Indonesia. Participants will be randomly divided into two groups: a Treatment Group receiving vaginal progesterone therapy and a Control Group receiving standard care without progesterone intervention. The primary outcomes are the prolongation of gestational age until delivery and the changes in cervical length over time. The secondary outcomes are recurrence of threatened preterm labor, mode of delivery, neonatal outcomes, and survival analysis. This study will provide valuable evidence supporting the use of vaginal progesterone as an effective intervention for women at risk of preterm labor and potentially improving maternal and neonatal outcomes in Indonesia and globally. All participants will be provided with detailed information about the study, and their participation will be voluntary. Ethical considerations, including informed consent and data confidentiality, will be strictly adhered to throughout the study.

Detailed description: This prospective, open-label, randomised clinical trial aims to investigate the effect of daily vaginal progesterone supplementation on pregnancy prolongation and cervical length changes following arrested preterm labor in singleton pregnancies. Threatened preterm labor is characterised by rhythmic uterine contractions occurring without substantial cervical changes, as assessed through digital pelvic examination. The gestational age will be verified via ultrasound metrics and review of antenatal care documentation. All subjects will receive standard tocolytic treatment, oral nifedipine for 48 hours in conjunction with dexamethasone injections to promote fetal lung development. The arrest of preterm labor is characterised by a stable condition that does not advance to active labor, specifically defined as two or fewer contractions per ten minutes, intact membranes, and cervical dilatation of three centimetres or less, following a minimum of 48 hours after the first dose of tocolytics. Women will be enrolled 48 hours after tocolytic initiation. Upon obtaining written informed consent from the participants, baseline data will be collected for each individual. The baseline data comprise demographic and clinical information, including risk factors, digital pelvic examinations, and ultrasound findings. All participants will receive a digital pelvic examination to assess cervical dilation and effacement, as well as a transvaginal ultrasound to measure cervical length. Cervical length will be assessed by Ernawati at Dr. Soetomo Hospital utilising a standard procedure with a probe encased in a disposable cover, which is then inserted vaginally with an empty bladder. The cervical length will be reassessed at outpatient clinic visits at 7 days and 14 days post-enrollment. Subsequent to the acquisition of baseline data, all participants will be randomly allocated into two groups: the Control Group, which does not receive therapy, and the Therapy Group, which will receive vaginal progesterone. Ethical considerations are of utmost importance in this study. The study protocol will undergo evaluation and approval by an Institutional Review Board (IRB) or equivalent ethical committee. Confidentiality of participants will be preserved during the study, and data will be anonymised throughout analysis and reporting. All potential hazards related to the examination or drug administration will be comprehensively communicated to participants, and suitable safety protocols will be established. Participants will be notified of their right to withdraw from the study at any period without penalty.

Eligibility criteria: Inclusion Criteria:

1. Singleton pregnant women who have passed the acute phase of Threatened Preterm Labor that meets the following criteria:

   1. Persistent contractions (2-3 contractions in 10 minutes) accompanied by cervical dilation assessed based on pelvic examination (Vaginal Touche)
   2. Intact amniotic membrane
   3. Cervical dilation ≤ 2 cm
   4. No birth occurs within 2x24 hours since persistent contractions appear.
2. Age 18-40 years
3. The gestational age must be between 28 weeks and 33 weeks plus 6 days.
4. Able to participate, communicate well with researchers, and willing to provide written consent to participate in the study.

Exclusion Criteria:

1. Patients with cervical cerclage in this pregnancy
2. Cervical length is less than 10 mm
3. Congenital abnormalities in the fetus
4. Anatomical abnormalities in the uterus
5. History of antepartum hemorrhage in this pregnancy
6. Known hypersensitivity to progesterone or contraindications to its use.
7. Suspected or proven premature rupture of membranes at enrollment
8. Subjects on drug therapy known to interact with progesterone (eg Bromocriptine, Rifampin, Ketoconazole, and Cyclosporine)
9. Subjects with comorbidities: cardiovascular disease, renal function, liver function, hematological disorders, and other uncontrolled comorbidities.
10. Subjects with stress conditions based on the DASS-42 questionnaire.

Primary outcomes:
measure: Prolongation of Gestation Age
timeFrame: Enrollment and Delivery
measure: Changes of Cervical Length
timeFrame: Enrollment, 7th and 14th day after enrollment
Secondary outcomes:
measure: Recurrence of Threatening Preterm Labor
timeFrame: 7th, 14th day after enrollment, and Delivery
measure: Delivery Method
timeFrame: Delivery
measure: APGAR Score
timeFrame: Delivery
measure: Baby Birth Weight
timeFrame: Delivery
measure: NICU Admission
timeFrame: Delivery
measure: Neonatal Mortality
timeFrame: Delivery and 28 days post partum
Other outcomes:
Locations:
city: Surabaya
country: Indonesia
facility: Dr. Soetomo General Hospital Surabaya
state: East Java
Study officials:
affiliation: Dr. Soetomo General Hospital Surabaya
name: Ernawati Ernawati, Dr.
role: PRINCIPAL_INVESTIGATOR
References: