Preterm LabourPhase 2NCT01429545
Single Versus Combination Therapy in Acute Tocolysis
A Phase 2 study testing Atosiban and Atosiban and nifedipine in people with Preterm Labour, run by Tawam Hospital at 2 sites in United Arab Emirates.
Trial summary
The purpose of this study is to compare the tocolytic efficacy, effectiveness and safety of Atosiban in comparison with the combination of Atosiban and Nifedipine together. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Preterm Labour
- What is being tested?
- Atosiban and Atosiban and nifedipine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 2 sitesUnited Arab Emirates
- Study dates
- Apr 2007to Mar 2011
- Phase
- Phase 2
- 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 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Clinical diagnosis of preterm labour
- Women with singleton pregnancies
Who cannot join
- Women with preterm prelabour rupture of membranes
- Women with any indication for emergency delivery for whom prolongation of pregnancy is contraindicated
Trial locations and contacts
2 sites in 1 country.
United Arab Emirates2 sites
Department of obstetrics and Gynecology, Tawam Hospital
Al Ain City, Abudhabi, 15258
Tawam Hospital
Al Ain City, Abudhabi, 15258
About this study
Official title: Phase 2 Study of Clinical Utility of Combination Tocolysis in Preterm Labor
The purpose of this study is to compare the tocolytic efficacy, effectiveness and safety of Atosiban in comparison with the combination of Atosiban and Nifedipine together.
Read the detailed description
Preterm birth, defined as birth at less than 37+0 weeks of gestation, is the most important determinant of adverse infant outcomes. It accounts for 5 to 11% of births in the world, but represents the single largest cause of mortality and morbidity for newborns and a major cause of morbidity for pregnant women. These babies are at increased risk of cerebral palsies, chronic pulmonary insufficiency and other handicaps resulting in suboptimal performance in school and decreased abstractive thinking compared with infants born at term. The economic burden on society in catering for these preterm babies is high. A multi-level modeling of hospital service utilization and cost profile of preterm birth done in 2005 in the United Kingdom, has outlined the huge economic consequences of preterm birth in the first 10 years of life. Furthermore, recent data from Denmark have shown an overall increase in the proportion of preterm deliveries by 22% from 1995 to 2004(from 5.2% to 6.3%). Neonatal mortality has declined, mostly due to improved management of very low birth weight babies rather than prevention of preterm labor (PTL).
The most common treatment used in the management of PTL involves pharmacological inhibition of preterm uterine contractions. Perinatal death and morbidity resulting from PTL are not only strongly related to early gestational age but also to antenatal administration of steroids and transfer to a tertiary care centre in utero or after birth.6 Hence, the choice of tocolytic agent depends on its ability to delay the delivery by at least 48 hours from the time of administration of steroids and preferably longer without maternal or fetal side effects. There is considerable variation in the type of tocolytic agent used in different parts of the world. Single agent tocolysis using ritodrine (β-agonist), atosiban (oxytocin antagonist) or nifedipine (calcium channel blocker) is a common practice. Atosiban has been shown to have comparable effectiveness to β-agonists but with improved side-effect profile similar to that seen in placebo studies. Meta analysis from Cochrane systematic review failed to demonstrate the superiority of atosiban over betamimetics or placebo in terms of tocolytic efficacy or infant outcomes, but, the maternal drug reactions that required treatment cessation were fewer with atosiban. Nifedipine is the only agent associated with improved perinatal outcomes and fewer maternal side-effects than betamimetics. A direct comparison between atosiban and nifedipine has shown that both drugs are equally effective in acute tocolysis, however maternal side-effects were more pronounced with nifedipine.
Due to the differences in their pharmacokinetics and pharmacodynamics, one may expect to have improved tocolysis when two agents are combined. In vitro studies have demonstrated that simultaneous blockade of these different pathways could result in an additive or even synergistic effect capable of producing better uterine relaxation than induced by each drug alone. Accordingly, the use of multiple agent therapies has been suggested as a way forward in tocolytic search. In an observational study, combination therapy without serious side effects has been used in the management of PTL at extremely early gestations by Ingemarsson et al.3 However, this was not tested in structured human trials.
The objective of this study was to compare the tocolytic efficacy and safety of the combination of atosiban and nifedipine against the single agent, atosiban in the treatment of PTL.
- Conditions
- Preterm Labour
- Being tested
- Atosiban, Atosiban and nifedipine
- Keywords
- Tocolysis, atosiban, nifedipine, combination
- Medical subject headings
- Obstetric Labor, Premature
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtosibanDrug
Also called Tractocile
Atosiban was given as a bolus (6.7 mg. IV) over 1 min then an infusion of 18 mg/hr for 3 hrs followed by 6 mg/hr for 48 hrs.
Atosiban and nifedipineDrug
Also called Tractocile and nifedipine
This group were given simultaneously as follows:Atosiban was given as a bolus (6.7 mg. IV) over 1 min then an infusion of 18 mg/hr for 3 hrs followed by 6 mg/hr for 48 hrs.Nifedipine was given in the dose of 10 mg orally every 15 min till uterine quiescence was achieved (<4 contractions/hr). Maximum dose was 40 mg in the first hour then maintenance dose of 10 mg every 4-6 h for 48 hrs was given.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 - Atosiban | Active comparator | Patients on single agent atosiban alone Receives: Drug: Atosiban |
| Group 2 | Experimental | Patients on combination of atosiban and nifedipine Receives: Drug: Atosiban and nifedipine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Safety was assessed by maternal, fetal and neonatal adverse events. Particular emphasis was placed on serious adverse cardiovascular events, including cardiac arrest, respiratory arrest, admission to intensive care unit and death were assessed as serious maternal outcomes and perinatal complications were recorded by neonatal morbidity and mortality until discharge from the hospital
Measured: Participants will be followed for the duration of pregnancy, an expected average of 10 weeks
Number of women undelivered 48 hrs and seven days of initiation of therapy
Tocolytic efficacy was assessed in terms of the proportion of women undelivered 48 hrs and seven days of initiation of therapy without the need for rescue tocolysis.
Measured: Participants who are not delivered within seven days of initiation of therapy
Number of Babies with Adverse Events as a Measure of Safety and Tolerability
Safety was assessed by maternal, fetal and neonatal adverse events. Perinatal complications were recorded by neonatal morbidity and mortality until discharge from the hospital
Measured: participants will be followed for the duration of hospital stay, an expected average of 7 weeks
Secondary outcomes (2)
Prolongation of pregnancy
Measured: Assessed till the date of delivery, an expected average of 10 weeks
Neonatal intensive care unit (NICU) admission
Number of neonates who are needing NICU admission after delivery.
Measured: Till the time of discharge, an expected avearge of 7 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2011 (estimated)
- Study startApr 2007
- Primary completionSep 2010
- Study completionMar 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Preterm LabourStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 110 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tawam Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Wafa Al Omari, Tawam Hospital
- Investigators
- Wafa R AlOmari, Principal investigator, Tawam Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01429545
- Sponsor's protocol ID
- 06/95
- Status last verified
- Sep 2011
- First submitted
- 1 Sep 2011
- Last updated
- 7 Sep 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Vogel JP, Nardin JM, Dowswell T, West HM, Oladapo OT. Combination of tocolytic agents for inhibiting preterm labour. Cochrane Database Syst Rev. 2014 Jul 11;2014(7):CD006169. doi: 10.1002/14651858.CD006169.pub2.
PubMed 25010869Doret M, Mellier G, Gaucherand P, Saade GR, Benchaib M, Frutoso J, Pasquier JC. The in vitro effect of dual combinations of ritodrine, nicardipine and atosiban on contractility of pregnant rat myometrium. BJOG. 2003 Aug;110(8):731-4.
PubMed 12892684Wilson A, Hodgetts-Morton VA, Marson EJ, Markland AD, Larkai E, Papadopoulou A, Coomarasamy A, Tobias A, Chou D, Oladapo OT, Price MJ, Morris K, Gallos ID. Tocolytics for delaying preterm birth: a network meta-analysis (0924). Cochrane Database Syst Rev. 2022 Aug 10;8(8):CD014978. doi: 10.1002/14651858.CD014978.pub2.
PubMed 35947046
Study at a glance
From the registry record, last updated by the sponsor on 7 Sep 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Study of Clinical Utility of Combination Tocolysis in Preterm Labor
- ClinicalTrials.gov ID
- NCT01429545
- Acronym / sponsor ID
- 06/95
- Conditions
- Preterm Labour
- Keywords
- Tocolysis, atosiban, nifedipine, combination
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 110 participants (actual)
- Lead sponsor
- Tawam HospitalUniversity, hospital or other
- Study start
- Apr 2007
- Primary completion
- Sep 2010 (actual)
- Study completion
- Mar 2011 (actual)
- First posted
- 7 Sep 2011 (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.
The purpose of this study is to compare the tocolytic efficacy, effectiveness and safety of Atosiban in comparison with the combination of Atosiban and Nifedipine together.
Detailed description
Preterm birth, defined as birth at less than 37+0 weeks of gestation, is the most important determinant of adverse infant outcomes. It accounts for 5 to 11% of births in the world, but represents the single largest cause of mortality and morbidity for newborns and a major cause of morbidity for pregnant women. These babies are at increased risk of cerebral palsies, chronic pulmonary insufficiency and other handicaps resulting in suboptimal performance in school and decreased abstractive thinking compared with infants born at term. The economic burden on society in catering for these preterm babies is high. A multi-level modeling of hospital service utilization and cost profile of preterm birth done in 2005 in the United Kingdom, has outlined the huge economic consequences of preterm birth in the first 10 years of life. Furthermore, recent data from Denmark have shown an overall increase in the proportion of preterm deliveries by 22% from 1995 to 2004(from 5.2% to 6.3%). Neonatal mortality has declined, mostly due to improved management of very low birth weight babies rather than prevention of preterm labor (PTL).
The most common treatment used in the management of PTL involves pharmacological inhibition of preterm uterine contractions. Perinatal death and morbidity resulting from PTL are not only strongly related to early gestational age but also to antenatal administration of steroids and transfer to a tertiary care centre in utero or after birth.6 Hence, the choice of tocolytic agent depends on its ability to delay the delivery by at least 48 hours from the time of administration of steroids and preferably longer without maternal or fetal side effects. There is considerable variation in the type of tocolytic agent used in different parts of the world. Single agent tocolysis using ritodrine (β-agonist), atosiban (oxytocin antagonist) or nifedipine (calcium channel blocker) is a common practice. Atosiban has been shown to have comparable effectiveness to β-agonists but with improved side-effect profile similar to that seen in placebo studies. Meta analysis from Cochrane systematic review failed to demonstrate the superiority of atosiban over betamimetics or placebo in terms of tocolytic efficacy or infant outcomes, but, the maternal drug reactions that required treatment cessation were fewer with atosiban. Nifedipine is the only agent associated with improved perinatal outcomes and fewer maternal side-effects than betamimetics. A direct comparison between atosiban and nifedipine has shown that both drugs are equally effective in acute tocolysis, however maternal side-effects were more pronounced with nifedipine.
Due to the differences in their pharmacokinetics and pharmacodynamics, one may expect to have improved tocolysis when two agents are combined. In vitro studies have demonstrated that simultaneous blockade of these different pathways could result in an additive or even synergistic effect capable of producing better uterine relaxation than induced by each drug alone. Accordingly, the use of multiple agent therapies has been suggested as a way forward in tocolytic search. In an observational study, combination therapy without serious side effects has been used in the management of PTL at extremely early gestations by Ingemarsson et al.3 However, this was not tested in structured human trials.
The objective of this study was to compare the tocolytic efficacy and safety of the combination of atosiban and nifedipine against the single agent, atosiban in the treatment of PTL.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 - Atosiban | Active comparator | Drug: AtosibanPatients on single agent atosiban alone |
| Group 2 | Experimental | Drug: Atosiban and nifedipinePatients on combination of atosiban and nifedipine |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Clinical diagnosis of preterm labour
- Women with singleton pregnancies
Key exclusion criteria (2 listed)
- Women with preterm prelabour rupture of membranes
- Women with any indication for emergency delivery for whom prolongation of pregnancy is contraindicated
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 |
|---|---|---|
| AtosibanAlso: TractocileAtosiban was given as a bolus (6.7 mg. IV) over 1 min then an infusion of 18 mg/hr for 3 hrs followed by 6 mg/hr for 48 hrs. | Drug | Group 1 - Atosiban |
| Atosiban and nifedipineAlso: Tractocile and nifedipineThis group were given simultaneously as follows:Atosiban was given as a bolus (6.7 mg. IV) over 1 min then an infusion of 18 mg/hr for 3 hrs followed by 6 mg/hr for 48 hrs.Nifedipine was given in the dose of 10 mg orally every 15 min till uterine quiescence was achieved (<4 contractions/hr). Maximum dose was 40 mg in the first hour then maintenance dose of 10 mg every 4-6 h for 48 hrs was given. | Drug | Group 2 |
Primary outcome
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time frame: Participants will be followed for the duration of pregnancy, an expected average of 10 weeks
Safety was assessed by maternal, fetal and neonatal adverse events. Particular emphasis was placed on serious adverse cardiovascular events, including cardiac arrest, respiratory arrest, admission to intensive care unit and death were assessed as serious maternal outcomes and perinatal complications were recorded by neonatal morbidity and mortality until discharge from the hospital
Number of women undelivered 48 hrs and seven days of initiation of therapy
Time frame: Participants who are not delivered within seven days of initiation of therapy
Tocolytic efficacy was assessed in terms of the proportion of women undelivered 48 hrs and seven days of initiation of therapy without the need for rescue tocolysis.
Number of Babies with Adverse Events as a Measure of Safety and Tolerability
Time frame: participants will be followed for the duration of hospital stay, an expected average of 7 weeks
Safety was assessed by maternal, fetal and neonatal adverse events. Perinatal complications were recorded by neonatal morbidity and mortality until discharge from the hospital
2 secondary outcomes
Prolongation of pregnancy
Time frame: Assessed till the date of delivery, an expected average of 10 weeks
Neonatal intensive care unit (NICU) admission
Time frame: Till the time of discharge, an expected avearge of 7 weeks
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 7 Sep 2011.
- Background: PubMed 25010869Vogel JP, Nardin JM, Dowswell T, West HM, Oladapo OT. Combination of tocolytic agents for inhibiting preterm labour. Cochrane Database Syst Rev. 2014 Jul 11;2014(7):CD006169. doi: 10.1002/14651858.CD006169.pub2.
- Results publication: PubMed 12892684Doret M, Mellier G, Gaucherand P, Saade GR, Benchaib M, Frutoso J, Pasquier JC. The in vitro effect of dual combinations of ritodrine, nicardipine and atosiban on contractility of pregnant rat myometrium. BJOG. 2003 Aug;110(8):731-4.
- Derived from this study: PubMed 35947046Wilson A, Hodgetts-Morton VA, Marson EJ, Markland AD, Larkai E, Papadopoulou A, Coomarasamy A, Tobias A, Chou D, Oladapo OT, Price MJ, Morris K, Gallos ID. Tocolytics for delaying preterm birth: a network meta-analysis (0924). Cochrane Database Syst Rev. 2022 Aug 10;8(8):CD014978. doi: 10.1002/14651858.CD014978.pub2.
- RCOG Guidelines No.1 (B) February 2011. Tocolytic drugs for women in preterm labour.Link provided by the sponsor.
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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.
Wafa R AlOmari principal investigator
Tawam Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Atosiban and Atosiban and nifedipine in people with Preterm Labour, run by Tawam Hospital at 2 sites in United Arab Emirates.
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 2 inclusion and 2 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 7 Sep 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Arab Emirates. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Number of Participants with Adverse Events as a Measure of Safety and Tolerability (time frame: Participants will be followed for the duration of pregnancy, an expected average of 10 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01429545, which also lists 3 linked publications.
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 7 Sep 2011.