Early vs Late Intervention for TRAP Syndrome

(TRAPIST Trial)

Recruiting at 13 trial locations

Overseen By Liesbeth Lewi, MD PhD

Age: 18+

Sex: Female

Trial Phase: Phase 4

Sponsor: Universitaire Ziekenhuizen Leuven

Disqualifiers: Severe maternal condition, Obesity, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

126 Participants Needed

Trial Summary

What is the purpose of this trial?

Multi-center open-label randomized controlled trial to assess if early intervention (12.0-14.0 weeks) (study group) improves the outcome of TRAP sequence as compared to late intervention (16.0-19.0 weeks) (control group). The investigators will randomly assign women diagnosed with TRAP sequence diagnosed between 12.0 and 13.6 weeks to an early or late intervention group (1:1), using a web-based application and a computer-generated list with random permuted blocks of sizes 2 or 4 (www.sealedenvelope.com), stratified by gestational age (GA) at inclusion (11.6 -12.6 weeks versus 13.0-13.6 weeks). Analysis will be by intention to treat.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is the treatment for TRAP sequence generally safe in humans?

The research does not provide specific safety data for the treatment of TRAP sequence, but it focuses on comparing different management approaches and outcomes. ^{1 2 3 4 5}

Research Team

Liesbeth Lewi, MD PhD

Principal Investigator

UZ Leuven

Eligibility Criteria

This trial is for women over 18 who can consent, with a monochorionic diamniotic twin pregnancy diagnosed with TRAP sequence between 11.6 and 13.6 weeks. The pump twin must be anatomically normal, and participants need to provide written informed consent.

Inclusion Criteria

Anatomically normal pump twin

TRAP sequence in a monochorionic diamniotic twin pregnancy diagnosed between 11.6 and 13.6 weeks, as determined by the crown-rump length of the pump twin in spontaneous conceptions and by the date of insemination or embryonic age at replacement in pregnancies resulting from subfertility treatment

I am a woman aged 18 or older and can give consent.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Early Intervention

Early selective reduction of TRAP mass between 12.0 and 14.0 weeks

2 weeks

1 visit (in-person)

Late Intervention

Late selective reduction of TRAP mass between 16.0 and 19.0 weeks

3 weeks

1 visit (in-person)

Follow-up

Participants are monitored for fetal well-being and development after intervention

Until 30 weeks gestation

3 visits (in-person) at 20 and 30 weeks, plus additional scans as needed

Treatment Details

Interventions

• Early selective reduction of TRAP mass
• Laser coagulation of the cord or anastomising vessels through a 17 Gauge to 7 French trocar, with a 1-1,3 mm fetoscope and a 400 µm laser fiber
• Late selective reduction of TRAP mass
• TRAP Intervention STudy
• Ultrasound-guided intrafetal ablation using a 17 to 20 Gauge needle
• Ultrasound-guided intrafetal ablation using a 18 to 20 Gauge needle

Trial Overview The study compares early (12-14 weeks) versus late (16-19 weeks) intervention in TRAP sequence pregnancies. Interventions include selective reduction of the TRAP mass or ultrasound-guided ablation using needles or laser coagulation through a trocar.

Participant Groups

Group I: Early intervention Experimental Treatment 2 Interventions

Intervention between 12.0 and 14.0 weeks. Early selective reduction of TRAP mass.

Group II: Late intervention Active Control 3 Interventions

Intervention between 16.0 and 19.0 weeks. Late selective reduction of TRAP mass. This is the standard timing of the intervention. One of two possible techniques for late reduction is chosen by the treating physician.

TRAP Intervention STudy is already approved in European Union, United States for the following indications:

Approved in European Union as TRAP Intervention for:

• Twin Reversed Arterial Perfusion Sequence

Approved in United States as TRAP Intervention for:

• Twin Reversed Arterial Perfusion Sequence

Who Is Running the Clinical Trial?

Universitaire Ziekenhuizen Leuven

Lead Sponsor

Trials

850

Recruited

1,233,000+

Universitaire Ziekenhuizen KU Leuven

Lead Sponsor

Trials

1,048

Recruited

1,658,000+

Sheba Medical Center Tel-Hashomer, Israel

Collaborator

Trials

1

Recruited

130+

St. George's Hospital, University of London (UK sponsor)

Collaborator

Trials

1

Recruited

130+

Leiden University Medical Center

Collaborator

Trials

580

Recruited

623,000+

Ospedalo Maggiore Policlinico di Milano, Italy

Collaborator

Trials

1

Recruited

130+

Hospital Universitari Vall d'hebron Barcelona, Spain

Collaborator

Trials

1

Recruited

130+

Centro Médico-Chirurgical et Obstétrical (CMCO) Schiltigheim, France

Collaborator

Trials

1

Recruited

130+

Universitätsklinik für Frauenheilkunde und Geburtshilfe Graz, Austria

Collaborator

Trials

1

Recruited

130+

Ospedale dei Bambini "Vittore Buzzi" Milano, Italy

Collaborator

Trials

1

Recruited

130+

Findings from Research

In a study of 40 cases of twin reversed arterial perfusion (TRAP) sequence, early intervention with interstitial laser therapy (Group B) resulted in lower rates of preterm premature rupture of membranes and higher gestational age and birth weight compared to expectant management or radiofrequency ablation (Group A).

The survival rates of the pump twin were similar between the two management approaches, indicating that while early intervention may improve pregnancy outcomes, it does not significantly affect the loss rate of the pump twin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early vs late intervention in twin reversed arterial perfusion sequence. Berg, C., Holst, D., Mallmann, MR., et al.[2014]

Intervention methods like cord occlusion or ablation significantly improve survival rates in cases of twin reversed arterial perfusion (TRAP) sequence compared to conservative management, with an odds ratio of 2.22 based on a systematic review of 26 studies.

Ablative techniques are particularly effective, showing even better survival outcomes than cord occlusion, with an odds ratio of 9.84, especially in the presence of poor prognostic indicators.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intervention versus a conservative approach in the management of TRAP sequence: a systematic review. Mone, F., Devaseelan, P., Ong, S.[2018]

In a study of 26 monochorionic twin pregnancies diagnosed with twin reversed arterial perfusion (TRAP) sequence, 33% of the pregnancies experienced spontaneous death of the pump twin before the planned intervention at 16-18 weeks.

The findings indicate a high mortality risk associated with TRAP sequence during the first to early second trimester, highlighting the urgency for timely intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The outcome of twin reversed arterial perfusion sequence diagnosed in the first trimester. Lewi, L., Valencia, C., Gonzalez, E., et al.[2016]

In a study of 12 pregnancies with twin reversed arterial perfusion (TRAP) sequence treated with intrafetal laser ablation (IFL) before 14 weeks of gestation, the procedure was technically successful with no cases of miscarriage or severe complications, but 41.7% of pregnancies experienced intrauterine death of the pump twin shortly after intervention.

Survivors of the procedure were treated at a later gestational age and had different growth ratios compared to non-survivors, suggesting that these factors may help predict outcomes, although none were definitive predictors of survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-trimester intervention in twin reversed arterial perfusion sequence: does size matter? Roethlisberger, M., Strizek, B., Gottschalk, I., et al.[2017]

In a study of six cases of twin reversed arterial perfusion (TRAP) sequence, conservative management was effective for milder cases where the pump twin was larger, leading to normal outcomes for two pregnancies.

In cases with signs of cardiac failure in the pump twin or where the acardiac twin was larger, in-utero YAG-laser occlusion of the umbilical vessels resulted in favorable outcomes, highlighting the importance of timely intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tailored management of twin reversed arterial perfusion (TRAP) sequence. Weisz, B., Peltz, R., Chayen, B., et al.[2016]

References

1. England pubmed.ncbi.nlm.nih.gov

Early vs late intervention in twin reversed arterial perfusion sequence. [2014]

2. Germany pubmed.ncbi.nlm.nih.gov

Intervention versus a conservative approach in the management of TRAP sequence: a systematic review. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

The outcome of twin reversed arterial perfusion sequence diagnosed in the first trimester. [2016]

4. England pubmed.ncbi.nlm.nih.gov

First-trimester intervention in twin reversed arterial perfusion sequence: does size matter? [2017]

5. England pubmed.ncbi.nlm.nih.gov

Tailored management of twin reversed arterial perfusion (TRAP) sequence. [2016]