Non-cephalic PresentationPhase 3REMIVERNCT01735669
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
A Phase 3 study testing Remifentanil and Nitrous Oxide in people with Non-cephalic Presentation and Inhalation of Nitrous Oxide, run by Hospital de Cruces at 1 site in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years, women only
- Conditions the study is for
- Non-cephalic Presentation, Inhalation of Nitrous Oxide, Pregnancy Complications
- What is being tested?
- Remifentanil and Nitrous Oxide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteSpain
- Study dates
- Jul 2012to Jan 2014
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- pregnancy at term (≥ 37 weeks)
- singleton foetus in non-cephalic presentation
- correct foetal cardiotocographic record
- obstetrical ultrasound examination without findings of serious foetal malformations
- indication for the performance of ECV
- acceptance of ECV
- age ≥ 18 years
- signature of informed consent
Who cannot join
- previous version in the same pregnancy (previous ECV in a different pregnancy allowed)
- 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;
- 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.
- contraindications for remifentanil: hypersensitivity to remifentanil, fentanyl or fentanyl analogs or to any component of its formulation (according to technical requirements by manufacturer).
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Non-cephalic Presentation, Inhalation of Nitrous Oxide, Pregnancy Complications, Complications; Cesarean Section, Fetus or Neonate Affected by External Version Before Labor
- Being tested
- Remifentanil, Nitrous Oxide
- Keywords
- Remifentanil, Breech presentation, Nitrous oxide, Pregnancy complications, Caesarean section, Fetal version
- Medical subject headings
- Pregnancy Complications, Breech Presentation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RemifentanilDrug
Also called CAS- NUMBER: 132875-61-7
Nitrous OxideDrug
Also called CAS_NUMBER:10024-97-2
| Study group | Role | What they receive |
|---|---|---|
| Remifentanil | Experimental | External cephalic version at term under Remifentanil perfusion Receives: Drug: Remifentanil |
| Nitrous oxide | Active comparator | External cephalic version at term under Nitrous oxide inhalation Receives: Drug: Nitrous Oxide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Success rate of ECV in singleton pregnancies in breech presentation at term
Measured: 5 minutes
Secondary outcomes (8)
Rate of adverse events and severity
Metrics (analysis)
Measured: 30 days
Pain Scores on the Visual Analog Scale
Metrics (scale)
Measured: 60 min
Rate of non-cephalic presentation in the delivery
Metrics (analysis)
Measured: 30 days
Caesarean rate
Metrics (analysis)
Measured: 30 days
Rate of women who would recommend the procedure
Metrics (questionnaire)
Measured: 60 min
Rate of women who would repeat the procedure
Metrics (questionnaire)
Measured: 60 min
Influence of the analgesia in the rate of women who would repeat the procedure
Metrics (questionnaire)
Measured: 60 min
Influence of the analgesia in the rate of women who would recommend the procedure
Metrics (questionnaire)
Measured: 60 min
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Nov 2012 (estimated)
- Study startJul 2012
- Primary completionApr 2013
- Study completionJan 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-cephalic PresentationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital de Cruces
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jorge Burgos, Hospital de Cruces
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01735669
- Sponsor's protocol ID
- REMIVER
- Acronym
- REMIVER
- Status last verified
- Feb 2015
- First submitted
- 20 Nov 2012
- Last updated
- 18 Feb 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01735669
- Acronym / sponsor ID
- REMIVER / REMIVER
- Conditions
- Non-cephalic Presentation, Inhalation of Nitrous Oxide, Pregnancy Complications, Complications; Cesarean Section, Fetus or Neonate Affected by External Version Before Labor
- Keywords
- Remifentanil, Breech presentation, Nitrous oxide, Pregnancy complications, Caesarean section, Fetal version
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- Hospital de CrucesUniversity, hospital or other
- Study start
- Jul 2012
- Primary completion
- Apr 2013 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 28 Nov 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Remifentanil | Experimental | Drug: RemifentanilExternal cephalic version at term under Remifentanil perfusion |
| Nitrous oxide | Active comparator | Drug: Nitrous OxideExternal cephalic version at term under Nitrous oxide inhalation |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- pregnancy at term (≥ 37 weeks)
- singleton foetus in non-cephalic presentation
- correct foetal cardiotocographic record
- obstetrical ultrasound examination without findings of serious foetal malformations
- indication for the performance of ECV
Key exclusion criteria (4 listed)
- previous version in the same pregnancy (previous ECV in a different pregnancy allowed)
- 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;
- 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.
- contraindications for remifentanil: hypersensitivity to remifentanil, fentanyl or fentanyl analogs or to any component of its formulation (according to technical requirements by manufacturer).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RemifentanilAlso: CAS- NUMBER: 132875-61-7 | Drug | Remifentanil |
| Nitrous OxideAlso: CAS_NUMBER:10024-97-2 | Drug | Nitrous oxide |
Primary outcome
Success rate of ECV in singleton pregnancies in breech presentation at term
Time frame: 5 minutes
8 secondary outcomes
Rate of adverse events and severity
Time frame: 30 days
Pain Scores on the Visual Analog Scale
Time frame: 60 min
Rate of non-cephalic presentation in the delivery
Time frame: 30 days
Caesarean rate
Time frame: 30 days
Rate of women who would recommend the procedure
Time frame: 60 min
Rate of women who would repeat the procedure
Time frame: 60 min
Influence of the analgesia in the rate of women who would repeat the procedure
Time frame: 60 min
Influence of the analgesia in the rate of women who would recommend the procedure
Time frame: 60 min
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2015.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Remifentanil and Nitrous Oxide in people with Non-cephalic Presentation and Inhalation of Nitrous Oxide, run by Hospital de Cruces at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Success rate of ECV in singleton pregnancies in breech presentation at term (time frame: 5 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Feb 2015.