Treatment of Classic Mid-trimester PPROM by Means of Continuous Amnioinfusion

NCT ID: NCT04696003

Last Updated: 2021-01-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

68 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-01-01

Study Completion Date

2025-05-30

Brief Summary

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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

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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 (7 days Amoxicillin/Clarithromycin therapy or 7 days Amoxicillin and once Azithromycin 1 g and corticosteroids' RDS prophylaxis).

Experimental group:

34 PPROM patients between 22/0 (20/0) -26/0 WG, continuous amnioinfusion (100 ml/h) in pregnant women with classic PPROM with oligo-/anhydramnion between 22/0- 26/0 weeks' gestation and systemic antibiotic therapy (7 days Amoxicil-lin/Clarythromycin or 7 days Amoxicillin and once Azithromycin 1 g) and corticosteroids' RDS prophylaxis.

Duration of intervention: Maximum till 34/0 weeks of gestation, or preterm delivery if indicated.

Follow-up per patient: 12 months post-partum. Subjects: Patients with classic PPROM between 22/0 (20/0) -26/0 WG. Primary efficacy endpoint: survival without major morbidity (severe bron-chopulmonary dysplasia (BPD), and/or grades 3 and 4 intraventricular hemor-rhage (IVH 3-4), and/or cystic periventricular leukomalacia (cPVL), and/or necrotizing enterocolitis (NEC)) since randomization (event time).

Expected outcome: The envestigators expect significant reduction of neonatal mortality and morbidity in the "Amnion-Flush" group.

Conditions

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Bronchopulmonary Dysplasia Necrotizing Enterocolitis Intracranial Hemorrhages

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

randomized multicenter controlled trial; two-arm parallel design.
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
The neonatal outcome will be evaluated one year after the delivery by the stuff of the University Center of the Clinical Studies.

Study Groups

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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.

Group Type NO_INTERVENTION

No interventions assigned to this group

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.

Group Type ACTIVE_COMPARATOR

Continuous amnioinfusion with Amnion Flush Solution through the intraamniotic catheter

Intervention Type COMBINATION_PRODUCT

The amniotic cavity will be punctured with a 18 gauge needle under ultrasound control. The intraamniotic catheter (0.65 mm Diameter, CE 0481, PakuMed GmbH, Essen, Germany) will be placed under local anesthesia with Xylocaine 1% 10 ml. and the amnioinfusion (about 100 ml/h, 2400 ml/day) with artificial amniotic fluid (Amnion Flush Solution, CE 0483, Serumwerk AG Bernburg, Germany) will be carried out with an infusion rate of 100 ml/h under periodic ultrasound using the standard i.v. pump.

Interventions

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Continuous amnioinfusion with Amnion Flush Solution through the intraamniotic catheter

The amniotic cavity will be punctured with a 18 gauge needle under ultrasound control. The intraamniotic catheter (0.65 mm Diameter, CE 0481, PakuMed GmbH, Essen, Germany) will be placed under local anesthesia with Xylocaine 1% 10 ml. and the amnioinfusion (about 100 ml/h, 2400 ml/day) with artificial amniotic fluid (Amnion Flush Solution, CE 0483, Serumwerk AG Bernburg, Germany) will be carried out with an infusion rate of 100 ml/h under periodic ultrasound using the standard i.v. pump.

Intervention Type COMBINATION_PRODUCT

Eligibility Criteria

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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
* labor
* 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).
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Martin-Luther-Universität Halle-Wittenberg

OTHER

Sponsor Role lead

Responsible Party

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Michael Tchirikov MD, PhD

Univ.-Prof. Dr. med.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Michael Tchirikov, MD, Ph.D.

Role: STUDY_DIRECTOR

University Clinic of Obstetrics and Prenatal Medicine

Locations

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Martin Luther University, Clinic of Obstetrics and Prenatal Medicine

Halle, Saxony-Anhalt, Germany

Site Status

Countries

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Germany

Central Contacts

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Michael Tchirikov, MD, Ph.D.

Role: CONTACT

-345-57-3250 ext. 049

Miriam Tchirikov, MD

Role: CONTACT

-345-57-3250 ext. 049

Facility Contacts

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Michael Tchirikov, MD, Ph.D.

Role: primary

0345-573250 ext. 049

Christian Haiduk

Role: backup

0345 557 4920 ext. 049

References

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Tchirikov M, Zhumadilov Z, Winarno AS, Haase R, Buchmann J. Treatment of Preterm Premature Rupture of Membranes with Oligo-/Anhydramnion Colonized by Multiresistant Bacteria with Continuous Amnioinfusion and Antibiotic Administrations through a Subcutaneously Implanted Intrauterine Port System: A Case Report. Fetal Diagn Ther. 2017;42(1):71-76. doi: 10.1159/000438483. Epub 2015 Oct 9.

Reference Type BACKGROUND
PMID: 26447923 (View on PubMed)

Tchirikov M, Bapayeva G, Zhumadilov ZSh, Dridi Y, Harnisch R, Herrmann A. Treatment of PPROM with anhydramnion in humans: first experience with different amniotic fluid substitutes for continuous amnioinfusion through a subcutaneously implanted port system. J Perinat Med. 2013 Nov;41(6):657-63. doi: 10.1515/jpm-2012-0296.

Reference Type BACKGROUND
PMID: 23774012 (View on PubMed)

Tchirikov M, Schlabritz-Loutsevitch N, Maher J, Buchmann J, Naberezhnev Y, Winarno AS, Seliger G. Mid-trimester preterm premature rupture of membranes (PPROM): etiology, diagnosis, classification, international recommendations of treatment options and outcome. J Perinat Med. 2018 Jul 26;46(5):465-488. doi: 10.1515/jpm-2017-0027.

Reference Type RESULT
PMID: 28710882 (View on PubMed)

Tchirikov M, Haiduk C, Tchirikov M, Riemer M, Bergner M, Li W, Henschen S, Entezami M, Wienke A, Seliger G. Treatment of Classic Mid-Trimester Preterm Premature Rupture of Membranes (PPROM) with Oligo/Anhydramnion between 22 and 26 Weeks of Gestation by Means of Continuous Amnioinfusion: Protocol of a Randomized Multicentric Prospective Controlled TRIAL and Review of the Literature. Life (Basel). 2022 Aug 30;12(9):1351. doi: 10.3390/life12091351.

Reference Type DERIVED
PMID: 36143388 (View on PubMed)

Other Identifiers

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2020-185

Identifier Type: -

Identifier Source: org_study_id

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