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
Condition: Non-cephalic Presentation; Inhalation of Nitrous Oxide; Pregnancy Complications; Complications; Cesarean Section; Fetus or Neonate Affected by External Version Before Labor
MeSH terms: Pregnancy Complications; Breech Presentation
Study type: Interventional
Phase: Phase 3

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.
    

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.
    

Intervention name(s): Remifentanil; Nitrous Oxide
Intervention type(s): Drug; Drug
Other intervention name(s): CAS- NUMBER: 132875-61-7; CAS_NUMBER:10024-97-2
Intervention MeSH terms: Remifentanil; Nitrous Oxide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Remifentanil; Breech presentation; Nitrous oxide; Pregnancy complications; Caesarean section; Fetal version