Open Randomized Controlled Trial to Evaluate the Efficacy and Safety of Remifentanil Versus Nitrous Oxide in External Cephalic Version at Term in Singleton Pregnancy in Breech Presentation (REMIVER)

Objectives: The objective is to demonstrate the superiority of remifentanil versus nitrous oxide as adjuvant analgesic treatment to increase the chances of success of external cephalic version in the management of non-cephalic presentation in women with singleton pregnancy at term. Another objective is to compare their safety, tolerability and acceptability.

Methodology: single-center clinical trial, randomized, open, parallel-group and sequential design, with active comparator. Pragmatic approach. Sequential design of O'Brien-Fleming with two interim analysis. Analysis by intention to treat. Comparison of the rate of successful version, referred to analgesic effect, safety, caesarean rates and acceptability rate of the procedure for pregnant women.

Study Overview

• Status: Completed
• Conditions: Pregnancy Complications; Inhalation of Nitrous Oxide; Complications; Cesarean Section; Non-cephalic Presentation; Fetus or Neonate Affected by External Version Before Labor
• Intervention / Treatment: Drug: Remifentanil; Drug: Nitrous Oxide

Detailed Description

External cephalic version is a procedure with clear benefits, but its realization is painful for the patient. Studies have shown that this pain limits external cephalic version efforts and therefore it negatively influences its success rate. In addition, any painful procedure has worse acceptance by patients so that its implementation is slow and not always universal. In this context, measures to reduce this pain could improve the success rate and acceptance of the procedure. All studies that have focused on reducing pain in external cephalic version have been made with regional anaesthetic techniques, epidural or spinal analgesia. Given the heterogeneity and the small number of studies there is still no conclusive data to make recommendations for regional anaesthesia in the external cephalic version. The introduction of regional anaesthesia can bring benefits to the version but it is not without drawbacks. This is an invasive anaesthetic technique that can reduce the security of the procedure and lead to longer hospital stay for the patient by the blockade that produces in the lower extremities. This in turn is associated with increased discomfort and costs of the procedure.

Cruces University Hospital has wide experience in carrying out external cephalic version procedures, being one of Spanish leading hospitals in terms of number of procedures and success rate. Currently external cephalic version procedures include analgesic support using nitrous oxide due to the combination of moderate analgesic activity and substantial ease of use.

The investigators belief is that the use of an opioid with advantageous pharmacokinetic properties and powerful analgesic effect as an adjunctive therapy during the course of external cephalic version procedures may become an efficacious and safe alternative, leading to increased pain relief and improved external cephalic version success rates. Its use requires, however, specific personnel and organizational facilities such as access to anesthetic support that can impede its widespread use. Therefore, the investigators is committed to explore feasibility and practical implementation factors as well as comparative efficacy and safety of this approach in non-cephalic presentation.

The investigators conducted a study to evaluate the effect of nitrous oxide as an adjunctive to external cephalic version and we observed a slight decrease in patient reported pain (visual analogous scale), with no effect on the rate of success. Currently, in the protocol of Cruces University Hospital the administration of nitrous oxide during the manoeuvres of the external cephalic version is routine practice. The investigators consider that the analgesic remifentanil is a better option for the external cephalic version than nitrous oxide by the combination of rapid onset of effect, with analgesic potency similar to regional anaesthesia and rapid metabolism that prevents their accumulation in tissues.

The lack of existing evidence on this issue, hence, prompts the investigators to conduct this pilot clinical trial aimed to assess scientific as well as logistical aspects involved in the performance of external cephalic version in non-cephalic presentation.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Bizkaia
    • Barakaldo, Bizkaia, Spain, 48903
      • Hospital Universitario Cruces

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. pregnancy at term (≥ 37 weeks)
2. singleton foetus in non-cephalic presentation
3. correct foetal cardiotocographic record
4. obstetrical ultrasound examination without findings of serious foetal malformations
5. indication for the performance of ECV
6. acceptance of ECV
7. age ≥ 18 years
8. signature of informed consent

Exclusion Criteria:

1. previous version in the same pregnancy (previous ECV in a different pregnancy allowed)
2. contraindications to ECV: 1-placenta praevia, 2- placental abruption, 3-oligohydramnios (SPD <2), 4-foetal compromise 5-foetal death, 6-severe malformations, 7-multiple pregnancy, 8- Rh sensitization, 9- uterine abnormalities, 10- clotting disorders;
3. contraindications to Nitrous Oxide: 1-patients who require pure oxygen ventilation 2- intracranial hypertension 3- disorders of consciousness that impede the cooperation of the patient, 4-pneumothorax; 5-emphysematous bulla, 6-pulmonary embolism; 7-immersion accident, 8-bloating abdominal trauma 9- facial trauma that affects the area of application of the mask,10- patients who received the type gases SF6, C3F8, C2F6 (used in eye surgery), at least in the previous three months.
4. contraindications for remifentanil: hypersensitivity to remifentanil, fentanyl or fentanyl analogs or to any component of its formulation (according to technical requirements by manufacturer).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Remifentanil; External cephalic version at term under Remifentanil perfusion	Drug: Remifentanil; Other Names: CAS- NUMBER: 132875-61-7
Active Comparator: Nitrous oxide; External cephalic version at term under Nitrous oxide inhalation	Drug: Nitrous Oxide; Other Names: CAS_NUMBER:10024-97-2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Success rate of ECV in singleton pregnancies in breech presentation at term	5 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of adverse events and severity	Metrics (analysis)	30 days
Pain Scores on the Visual Analog Scale	Metrics (scale)	60 min
Rate of non-cephalic presentation in the delivery	Metrics (analysis)	30 days
Caesarean rate	Metrics (analysis)	30 days
Rate of women who would recommend the procedure	Metrics (questionnaire)	60 min
Rate of women who would repeat the procedure	Metrics (questionnaire)	60 min
Influence of the analgesia in the rate of women who would repeat the procedure	Metrics (questionnaire)	60 min
Influence of the analgesia in the rate of women who would recommend the procedure	Metrics (questionnaire)	60 min

Collaborators and Investigators

• Sponsor: Hospital de Cruces

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: November 20, 2012
• First Submitted That Met QC Criteria: November 25, 2012
• First Posted (Estimate): November 28, 2012

Study Record Updates

• Last Update Posted (Estimate): February 18, 2015
• Last Update Submitted That Met QC Criteria: February 14, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Keywords: Remifentanil; Caesarean section; Pregnancy complications; Nitrous oxide; Breech presentation; Fetal version
• Additional Relevant MeSH Terms: Obstetric Labor Complications; Pregnancy Complications; Breech Presentation; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Analgesics, Opioid; Narcotics; Anesthetics, Inhalation; Remifentanil; Nitrous Oxide
• Other Study ID Numbers: REMIVER