Treatment of Classic Mid-trimester Preterm Premature Rupture of Membranes (PPROM) With Oligo/Anhydramnion Between 22/0-26/0 Week of Gestation by Means of Continuous Amnioinfusion: a Multicenter Prospectiv Randomized Trial
Trial Snapshot
- Phase
- Phase 3
- Status
- Not yet recruiting
- Enrollment
- 68
- Locations
- 1
- Primary Endpoint
- Number of Participants with bronchopulmonary dysplasia
Study Overview
Brief Summary
Objective: Mid-trimester preterm premature rupture of membranes (PPROM), defined as rupture of fetal mem-branes prior to 28 weeks' gestation (WG), complicates approximately 0.4-0.7% of all pregnancies and associated with very high neonatal mortality and morbidity. Antibiotics have limited success to prevent bacteremia, chorioamnionitis and fetal inflammation because of reduced placental transport. The repetitive amnioinfusion doesn't work because of immediately fluid lost after the intervention). The continuous amnioinfusion with Amnion Flush Solution through the perinatal port system in patients with classic PPROM prolonged the PPROM-to-delivery interval to 49 days in average by flush out of bacteria and inflammatory components from the amniotic cavity.
Aim: This multicenter trial tests the effect of continuous amnioinfusion on the neonatal survival without major morbidities, like severe bronchopulmonary dysplasia, intraventricular hemorrhage, cystic periventricular leukomalacia and necrotizing enterocolitis.
Design: randomized multicenter controlled trial; two-arm parallel design. Control group: 34 PPROM patients between 22/0 (20/0) -26/0 WG treating with antibiotics and corticosteroids in according to DGGG guide-lines. In interventional group (n=34) the standard PPROM therapy will be complemented by "Amnion -Flush" method with the amnioinfusion of artificial amniotic fluid (Amnion Flush Solution, Serumwerk AG, Germany, 2400 ml/d).
Subjects: Patients with classic PPROM between 22/0-26/0 WG. Expected outcome:The investigators expect significant reduction of neonatal mortality and morbidity in the "Amnion-Flush" group.
Detailed Description
Objective:
Mid-trimester preterm premature rupture of membranes (PPROM), defined as rupture of fetal mem-branes prior to 28 weeks' gestation (WG), complicates approximately 0.4-0.7% of all pregnancies and associated with very high neonatal mortality and morbidity. Antibiotics have limited success to prevent bacteremia, chorioamnionitis and fetal inflammation because of reduced placental transport. The repetitive amnioinfusion doesn't work because of immediately fluid lost after the intervention). The continuous amnioinfusion with Amnion Flush Solution through the perinatal port system in patients with classic PPROM prolonged the PPROM-to-delivery interval to 49 days in average by flush out of bacteria and inflammatory components from the amniotic cavity.
Aim: This multicenter trial tests the effect of continuous amnioinfusion on the neonatal survival without major morbidities, like severe bronchopulmonary dysplasia, intraventricular hemorrhage, cystic periventricular leukomalacia and necrotizing enterocolitis.
Design: randomized multicenter controlled trial; two-arm parallel design.
Control group:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Outcomes Assessor)
Masking Description
The neonatal outcome will be evaluated one year after the delivery by the stuff of the University Center of the Clinical Studies.
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Singleton pregnancy (from 22/0 to 26/0 weeks of gestation)
- •Evidence of PPROM from clinical and instrumental investigations
- •Oligo/anhydramnion (< 2 cm deepest amniotic fluid pocket)
Exclusion Criteria
- •fetal death
- •placental abnormalities
- •evidence of major structural or chromosomal abnormalities
- •signs of chorioamnionitis (maternal fever > 38° C and one or more of the following criteria: uterine tenderness, malodorous vag-inal discharge, maternal leukocytosis > 15000 cells/mm3, maternal tachycardia > 100 beats/min, and fetal heart rate > 160 bpm).
Arms & Interventions
control
The patients with classic PPROM between 22/0-26/0 weeks' gestation with oligo/anhydramnion with standard conservative treatment (7 days Amoxicillin/Clarithromycin therapy or 7 days Amoxicillin and once Azithromycin 1 g per os, and corticosteroids like Celestan®, Essex Pharma, Munich, Germany) as RDS prophylaxis will represent the control group (DGGG Guideline AWMF 015-025, February 2019, Version 1.0). The diagnosis of the PPROM must be not early than 20/0 weeks' gestation.
Amnion Flush group (continuous amnioinfusion)
In the "Amnion Flush" group additionally to the standard treatment the amniotic cavity will be punctured with a 18 gauge needle under ultrasound control. The intra-amniotic catheter (0.65 mm Diameter, CE 0481, PakuMed GmbH, Essen, Germany) will be placed under local anesthesia with Xylocaine 1% 10 ml. Amnion Flush Solution (CE 0483, Serumwerk AG Bernburg, Germany) will be carried out with an infusion rate of 100 ml/h (2400 ml/d) under periodic ultrasound using the standard i.v. pump. The deepest pool of amniotic fluid should be stabilized by about 4 cm. The ultrasound control will be performed daily. Induction of the labour or c-section at 34/0 week of gestation or earlier if indicated.
Intervention: Continuous amnioinfusion with Amnion Flush Solution through the intraamniotic catheter (Combination Product)
Outcomes
Primary Outcomes
Number of Participants with bronchopulmonary dysplasia
Time Frame: through study completion, an average of 1 year
Number of Participants with severe bronchopulmonary dysplasia (BPD)
Number of Participants with intraventricular hemorrhage
Time Frame: through study completion, an average of 1 year
Number of Participants with intraventricular hemorrhage (IVH 3-4)
Number of Participants with necrotizing enterocolitis
Time Frame: through study completion, an average of 1 year
Number of Participants with necrotizing enterocolitis (NEC)
Secondary Outcomes
- Duration of PPROM to delivery interval(up to 15 weeks)
- Gesatational age at delivery(34 weeks)
- Rate of Newborns with FIRS(1 week)
Investigators
Michael Tchirikov MD, PhD
Univ.-Prof. Dr. med.
Martin-Luther-Universität Halle-Wittenberg