Clinical trial NCT02597699: Use of Ultiva ® Associated With Xylocaine ® in the Procedures of Feticide
Official title: Use of Ultiva ® Associated With Xylocaine ® in the Procedures of Feticide: A Phase III Randomized Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Termination of Pregnancy
Feticide
Keywords: Termination of pregnancy
Feticide
Fetal pain
Remifentanil Ultiva®
Fetal asystole
Fetopathologic analysis
Lead sponsor: University Hospital, Montpellier
Sponsor class: OTHER
Collaborators: name: Centre Hospitalier Universitaire de Nīmes
First posted: 2015-11-05
Enrollment: 66
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The feticide is a legal and ethical obligation during a termination of pregnancy after 22 weeks' gestation. This method raise concerns about the fetal pain, maternal complications and the fetopathologic analysis. There are few studies on the subject. Investigators want to evaluate a drug in order to facilitate this method technically and emotionally challenging. They want to achieve a quick fetal asystole, a fetal analgesia, a maternal security and a optimal fetopathologic analysis. A drug, remifentanil Ultiva®, seems could meet its properties, it is a powerful morphine. A phase 2 clinical trial has assessed the feasibility, efficacy and safety of Ultiva®. They had not been able to prove bradycardia or lethal effect of Ultiva injected alone but the feasibility and safety were good.

Investigators want to set up a randomized clinical trial with 2 arms : Ultiva® and lidocaine versus sufentanil and lidocaine (standard protocol), it is a bicentric study. The primary outcome is the interval between the vascular injection of lidocaine and fetal asystole. The secondary outcomes are the success rate of method, the number of puncture of the umbilical cord, the maternal side effects and the quality of fetopathologic analysis.

The previous observational study showed a median interval of 2,3 minutes and a success rate of 55% (lower interval to 2 minutes). From the results they calculate a necessary inclusions to 66 patients.

They believe that the bradycardia property of Ultiva® allow a potentiation of the efficacy of lidocaine. If the results are satisfactory, the use of Ultiva® can be generalized to other fetal medicine team.

Detailed description: The intervention will take place, as in the framework of usual care, obstetric block after achievement of maternal locoregional anesthesia peri-rachianesthesia, skin disinfection and sterile field. The gesture will be performed by an experienced obstetrician under ultrasound guidance. Anesthetist-resuscitator is present in the obstetric block. Peri-rachianesthesia is performed by the initial injection of 2.5mg of hyperbaric bupivacaine associated with 5 gamma of Sufentanil and 0.5ml of physiological saline.

Inclusion in one of two arms is defined after randomization in single blind:

Arm 1 (Sufentanil + Lidocaïne) or Arm 2 (Ultiva® + Lidocaïne) For patients randomized in the arm 1, we will realize the reference protocol, as in the current practice, by injecting Sufentanil intra-cordally at the posology of 1,5 μg / kg of estimated fetal weight, then Lidocaïne 1% in bolus of 10 ml (10 mg / ml).

If 2 minutes after the start of the injection of Lidocaïne, there is no obtaining of fetal asystole, we will inject 100 mg of Lidocaïne 1% into a 10 ml bolus. In case of failure of the procedure, we will inject 10ml of KCL 10% intra-cordial if the cord is still accessible, if not intra-cardiac.

For patients randomized to arm 2, we will intracenally inject Ultiva® 30 μg and Lidocaïne 1% into 10 ml bolus (10 mg / ml).

If 2 minutes after the start of the injection of Lidocaïne, there is no obtaining of asystole, we will inject 100 mg of Lidocaïne 1% in 10 ml bolus. In case of failure of the procedure, we will inject 10 ml of KCL 10% intra-cordally if the cord is still accessible, if not intra-cardiac.

Eligibility criteria: Inclusion Criteria:

1. Age \> = 18 years
2. Patient having received an authorization of medical termination of pregnancy beyond 22 weeks of amenorrhea by the Multidisciplinary Centers of Prenatal Diagnosis of Montpellier or Nimes
3. Patient member or beneficiary of a national insurance scheme
4. Patient capable of understanding the nature, the purpose and the methodology of the trial
5. Patient having given an informed consent signed before the inclusion in the trial

Exclusion Criteria:

1. Patient presenting a selective or total feticide in the cases of multiple pregnancies (the first preferential way in these cases is intracardiac, moreover the act risks to be complicated by the active movements of the other foetus)
2. Major Patient protected by the law (guardianship, curators, or under protection of justice)
3. Patient deprived of freedom by court or administrative order

Primary outcomes:
measure: The deadline of obtaining the asystole
timeFrame: up to 5 minutes
Secondary outcomes:
measure: The success rate of the procedure of foeticide
timeFrame: within 2 minutes after injection of Lidocaïne and persistent during at least 1 minute
measure: The number of new punction(s) of the cordon
timeFrame: 1 day
measure: Number of side effects
timeFrame: 1 day
measure: The quality of tissues (the fetopathologic analysis)
timeFrame: 1 day
Other outcomes:
Locations:
city: Montpellier
country: France
facility: Hôpital Arnaud de Villeneuve
city: Nimes
country: France
facility: Nîmes University Hospital
Study officials:
affiliation: Montpellier University Hospital
name: Romy RR RAYSSIGUIER, MD
role: PRINCIPAL_INVESTIGATOR
References: