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Bronchopulmonary DysplasiaPhase 3AmnionFlushNCT04696003

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

A Phase 3 study testing Continuous amnioinfusion with Amnion Flush Solution through the intraamniotic catheter in people with Bronchopulmonary Dysplasia and Necrotizing Enterocolitis, run by Martin-Luther-Universität Halle-Wittenberg at 1 site in Germany.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women onlyHealthy volunteers can take part
What is being tested?
Continuous amnioinfusion with Amnion Flush Solution through the intraamniotic catheter
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
68 participants
Where
1 siteGermany
Study dates
1 Jan 2021to 30 May 2025
Phase
Phase 3
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

  • 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)

Who cannot join

  • 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).

Trial locations and contacts

1 site in 1 country.

Germany1 site
  • Martin Luther University, Clinic of Obstetrics and Prenatal Medicine

    Halle, Saxony-Anhalt, 06120

    Michael Tchirikov, MD, Ph.D., 0345-573250 ext. 049, michael.tchirikov@uk-halle.de

    Christian Haiduk, 0345 557 4920 ext. 049, Haiduk.Christian@kks-halle.de

Other trials in Germany

About this study

Official title: 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

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.

Read more

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.

Read the 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:

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.

Being tested
Continuous amnioinfusion with Amnion Flush Solution through the intraamniotic catheter
Keywords
PPROM, Amnion Flush Solution, outcome, amnioinfusion
Medical subject headings
Bronchopulmonary Dysplasia, Enterocolitis, Necrotizing, Intracranial Hemorrhages, Preterm Premature Rupture of the Membranes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Continuous amnioinfusion with Amnion Flush Solution through the intraamniotic catheterCombination 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.

Study groups in NCT04696003
Study groupRoleWhat they receive
controlNo interventionThe 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)Active comparatorIn 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.
Receives: Combination Product: Continuous amnioinfusion with Amnion Flush Solution through the intraamniotic catheter

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants with bronchopulmonary dysplasia

    Number of Participants with severe bronchopulmonary dysplasia (BPD)

    Measured: through study completion, an average of 1 year

  2. Number of Participants with intraventricular hemorrhage

    Number of Participants with intraventricular hemorrhage (IVH 3-4)

    Measured: through study completion, an average of 1 year

  3. Number of Participants with necrotizing enterocolitis

    Number of Participants with necrotizing enterocolitis (NEC)

    Measured: through study completion, an average of 1 year

Secondary outcomes (3)
  1. Duration of PPROM to delivery interval

    Duration of PPROM to delivbery interval (days)

    Measured: up to 15 weeks

  2. Gesatational age at delivery

    gestational age at delivery

    Measured: 34 weeks

  3. Rate of Newborns with FIRS

    Rate of Newborns with FIRS (fetal inflammatory response syndrome) (binary)

    Measured: 1 week

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Jan 2021
  2. Study start1 Jan 2021 (estimated)
  3. Primary completion31 Aug 2024 (estimated)
  4. Study completion30 May 2025 (estimated)

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
randomized multicenter controlled trial; two-arm parallel design.
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
68 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04696003
Sponsor's protocol ID
2020-185
Acronym
AmnionFlush
Status last verified
Jan 2021
First submitted
21 Dec 2020
Last updated
12 Jan 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 26447923
  • 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.

    PubMed 23774012
  • 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.

    PubMed 28710882
  • 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.

    PubMed 36143388

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Continuous amnioinfusion with Amnion Flush Solution through the intraamniotic catheter in people with Bronchopulmonary Dysplasia and Necrotizing Enterocolitis, run by Martin-Luther-Universität Halle-Wittenberg at 1 site in Germany.

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 3 inclusion and 5 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 12 Jan 2021. 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 Germany. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 Michael Tchirikov, MD, Ph.D. (-345-57-3250 ext. 049, michael.tchirikov@uk-halle.de), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants with bronchopulmonary dysplasia (time frame: through study completion, an average of 1 year). The study lists 3 primary outcomes in all. 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 NCT04696003, which also lists 4 linked publications.

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 12 Jan 2021.

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