Single Versus Combination Therapy in Acute Tocolysis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Wafa Al Omari, Tawam Hospital
ClinicalTrials.gov Identifier:
NCT01429545
First received: September 1, 2011
Last updated: September 6, 2011
Last verified: September 2011
  Purpose

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.


Condition Intervention Phase
Preterm Labour
Drug: Atosiban
Drug: Atosiban and nifedipine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 2 Study of Clinical Utility of Combination Tocolysis in Preterm Labor

Resource links provided by NLM:


Further study details as provided by Tawam Hospital:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    Safety was assessed by maternal, fetal and neonatal adverse events. Perinatal complications were recorded by neonatal morbidity and mortality until discharge from the hospital


Secondary Outcome Measures:
  • Prolongation of pregnancy [ Time Frame: Assessed till the date of delivery, an expected average of 10 weeks ] [ Designated as safety issue: No ]
  • Neonatal intensive care unit (NICU) admission [ Time Frame: Till the time of discharge, an expected avearge of 7 weeks ] [ Designated as safety issue: No ]
    Number of neonates who are needing NICU admission after delivery.


Enrollment: 110
Study Start Date: April 2007
Study Completion Date: March 2011
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Group 1 - Atosiban
Patients on single agent atosiban alone
Drug: Atosiban
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.
Other Name: Tractocile
Experimental: Group 2
Patients on combination of atosiban and nifedipine
Drug: Atosiban 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.
Other Name: Tractocile and nifedipine

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.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Clinical diagnosis of preterm labour
  • Women with singleton pregnancies

Exclusion Criteria:

  • Women with preterm prelabour rupture of membranes
  • Women with any indication for emergency delivery for whom prolongation of pregnancy is contraindicated
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01429545

Locations
United Arab Emirates
Department of obstetrics and Gynecology, Tawam Hospital
Al Ain, Abudhabi, United Arab Emirates, 15258
Tawam Hospital
Al Ain, Abudhabi, United Arab Emirates, 15258
Sponsors and Collaborators
Tawam Hospital
Investigators
Principal Investigator: Wafa R AlOmari Tawam Hospital
  More Information

Additional Information:
Publications:
Responsible Party: Wafa Al Omari, Consultant Obstetrics and gynecolgy, Tawam Hospital
ClinicalTrials.gov Identifier: NCT01429545     History of Changes
Other Study ID Numbers: 06/95
Study First Received: September 1, 2011
Last Updated: September 6, 2011
Health Authority: United Arab Emirates: General Authority for Health Services for Abu Dhabi

Keywords provided by Tawam Hospital:
Tocolysis
atosiban
nifedipine
combination

Additional relevant MeSH terms:
Obstetric Labor, Premature
Obstetric Labor Complications
Pregnancy Complications
Atosiban
Nifedipine
Calcium Channel Blockers
Cardiovascular Agents
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses
Tocolytic Agents
Vasodilator Agents

ClinicalTrials.gov processed this record on October 23, 2014