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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01735669
Recruitment Status : Completed
First Posted : November 28, 2012
Last Update Posted : February 18, 2015
Information provided by (Responsible Party):
Jorge Burgos, Hospital de Cruces

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Non-cephalic Presentation Inhalation of Nitrous Oxide Pregnancy Complications Complications; Cesarean Section Fetus or Neonate Affected by External Version Before Labor Drug: Remifentanil Drug: Nitrous Oxide Phase 3

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  (Clinical Trial)
Actual Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : July 2012
Actual Primary Completion Date : April 2013
Actual Study Completion Date : January 2014

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Remifentanil
External cephalic version at term under Remifentanil perfusion
Drug: Remifentanil
Other Name: CAS- NUMBER: 132875-61-7

Active Comparator: Nitrous oxide
External cephalic version at term under Nitrous oxide inhalation
Drug: Nitrous Oxide
Other Name: CAS_NUMBER:10024-97-2

Primary Outcome Measures :
  1. Success rate of ECV in singleton pregnancies in breech presentation at term [ Time Frame: 5 minutes ]

Secondary Outcome Measures :
  1. Rate of adverse events and severity [ Time Frame: 30 days ]
    Metrics (analysis)

  2. Pain Scores on the Visual Analog Scale [ Time Frame: 60 min ]
    Metrics (scale)

  3. Rate of non-cephalic presentation in the delivery [ Time Frame: 30 days ]
    Metrics (analysis)

  4. Caesarean rate [ Time Frame: 30 days ]
    Metrics (analysis)

  5. Rate of women who would recommend the procedure [ Time Frame: 60 min ]
    Metrics (questionnaire)

  6. Rate of women who would repeat the procedure [ Time Frame: 60 min ]
    Metrics (questionnaire)

  7. Influence of the analgesia in the rate of women who would repeat the procedure [ Time Frame: 60 min ]
    Metrics (questionnaire)

  8. Influence of the analgesia in the rate of women who would recommend the procedure [ Time Frame: 60 min ]
    Metrics (questionnaire)

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01735669

Hospital Universitario Cruces
Barakaldo, Bizkaia, Spain, 48903
Sponsors and Collaborators
Hospital de Cruces

Responsible Party: Jorge Burgos, PROFESSOR, Hospital de Cruces Identifier: NCT01735669     History of Changes
Other Study ID Numbers: REMIVER
First Posted: November 28, 2012    Key Record Dates
Last Update Posted: February 18, 2015
Last Verified: February 2015

Keywords provided by Jorge Burgos, Hospital de Cruces:
Breech presentation
Nitrous oxide
Pregnancy complications
Caesarean section
Fetal version

Additional relevant MeSH terms:
Pregnancy Complications
Breech Presentation
Obstetric Labor Complications
Nitrous Oxide
Analgesics, Opioid
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Hypnotics and Sedatives
Anesthetics, Intravenous
Anesthetics, General
Anesthetics, Inhalation
Analgesics, Non-Narcotic