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.
Inhalation of Nitrous Oxide
Complications; Cesarean Section
Fetus or Neonate Affected by External Version Before Labor
Drug: Nitrous Oxide
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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|
- Success rate of ECV in singleton pregnancies in breech presentation at term [ Time Frame: 5 minutes ] [ Designated as safety issue: No ]
- Rate of adverse events and severity [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]Metrics (analysis)
- Pain Scores on the Visual Analog Scale [ Time Frame: 60 min ] [ Designated as safety issue: No ]Metrics (scale)
- Rate of non-cephalic presentation in the delivery [ Time Frame: 30 days ] [ Designated as safety issue: No ]Metrics (analysis)
- Caesarean rate [ Time Frame: 30 days ] [ Designated as safety issue: No ]Metrics (analysis)
- Rate of women who would recommend the procedure [ Time Frame: 60 min ] [ Designated as safety issue: No ]Metrics (questionnaire)
- Rate of women who would repeat the procedure [ Time Frame: 60 min ] [ Designated as safety issue: No ]Metrics (questionnaire)
- Influence of the analgesia in the rate of women who would repeat the procedure [ Time Frame: 60 min ] [ Designated as safety issue: No ]Metrics (questionnaire)
- Influence of the analgesia in the rate of women who would recommend the procedure [ Time Frame: 60 min ] [ Designated as safety issue: No ]Metrics (questionnaire)
|Study Start Date:||July 2012|
|Study Completion Date:||January 2014|
|Primary Completion Date:||April 2013 (Final data collection date for primary outcome measure)|
External cephalic version at term under Remifentanil perfusion
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
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01735669
|Hospital Universitario Cruces|
|Barakaldo, Bizkaia, Spain, 48903|