- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00137501
Two Dose Regimens of Nifedipine for the Management of Preterm Labor
Study of Different Doses of Nifedipine to Treat Preterm Labor
Study Overview
Detailed Description
RESEARCH DESIGN AND METHODS
Inclusion criteria:
- All pregnant women diagnosed with preterm labor defined as regular contractions associated with cervical change between 24 and 34 weeks of gestation.
Exclusion criteria:
- Multiple pregnancy
- Preterm rupture of membranes
- Congenital fetal malformations
- IUGR (intra uterine growth restriction)
- Previous tocolysis this pregnancy
- Chorioamnionitis
- Cervical dilation > 4 cms
- Maternal medical conditions such as renal insufficiency, hepatic insufficiency, or myasthenia gravis
- Non-reassuring fetal heart rate
- Maternal hypotension, defined as a blood pressure < 90/50 mm Hg
Randomization procedure:
Randomization envelopes will be prepared by means of a random number table. After informed consent is obtained, the next numbered opaque envelope will be opened to assign each patient to receive either the low or high nifedipine dose regimen. Because of the different doses of nifedipine, neither patients nor physicians will be blinded to treatment allocation.
Routine studies and procedures:
- A baseline ECG will be performed before starting the medication.
- All patients will receive a 500-mL intravenous bolus of isotonic sodium chloride solution unless they have clinical volume overload, followed by a maintenance administration of 125 mL/h.
- Maternal blood pressure and heart rate will be recorded every 15 minutes as long as the patient is in labor and every 4 hours thereafter.
- Fetal heart rate and uterine activity were monitored continuously throughout the study period.
- All patients eligible for the study will receive antibiotic prophylaxis for Group B Streptococcal infection (IV Pen G or Ampicillin) for at least 48 hours, pending the vaginorectal swab culture that is done routinely on every patient presenting with preterm labor.
- All patients will receive one course of 12 mg betamethasone intramuscularly every 24 hours for 48 hours to promote fetal lung maturation and a rescue dose if they present in labor again at < 34 weeks of gestation.
Interventions:
First arm (high dose):
Nifedipine (Adalat®) 20 mg sublingual crushed, repeated after 30 minutes if contractions do not decrease in intensity. Maintenance of 120-160 mgs of slow-release nifedipine (Nifedicor®) daily for 48 hours (30 mg Q 6 hrs up to a maximum of 40 mg Q 6 hrs). Once contractions cease, nifedipine will be maintained at 80-120 mg daily in divided doses up to 36 weeks of gestation on an outside basis.
Second arm (low dose):
Nifedipine (Adalat®) 10 mg sublingual crushed, then 10 mg sublingual in 15 min, followed by 10 mg PO Q 15 mins PRN to a maximum of 40 mg in the first hour. Maintenance of 60-80 mgs of slow-release nifedipine (Nifedicor®) daily for 48 hours (20 mg Q 8 hrs or 20 mg Q 6 hrs). Once contractions cease, nifedipine will be maintained at 60 mg daily in divided doses up to 36 weeks of gestation.
- Tocolysis will be considered to be achieved when uterine activity decrease to <4 contractions/h with the absence of cervical change.
- If patients continue to have uterine activity after 6 hours or have cervical dilatation >2 cm after admission examination, they could be switched to another tocolytic regimen, namely intravenous MgSO4 or intravenous ritodrine.
Written Consent:
The written consent will be handed to every pregnant patient eligible for this study. She will be given enough time to read it and decide whether she is willing to participate in the trial.
Outcome variables studied:
- Speed of onset of uterine quiescence
- Uterine quiescence at 6 hours of initiating therapy
- Delivery >48 hours from initiation of therapy
- Delivery >7 days from initiation of therapy
- Delivery <37 weeks of gestation
- Delivery at <34 weeks of gestation
- Side effects to nifedipine
- Maternal adverse drug reactions requiring cessation of treatment
- Antepartum hemorrhage
- Maternal length of hospital stay
- Pregnancy prolongation
- Postpartum hemorrhage
- Birthweight
- Apgar score <7 at 5 min
- Admission to NICU
- Mechanical ventilation
- RDS (respiratory distress syndrome)
- IVH all grades
- Neonatal nursery stay
- Neonatal jaundice
- NEC (Necrotizing enterocolitis)
- Neonatal death
Side effects associated with nifedipine include a mild decrease in blood pressure and a rise in pulse, headache, flushing, dizziness and nausea.
Data Collection:
The initial information in the data sheets will be filled by the resident in charge of delivery suite. However, the follow up on the response of the patients to the medication and data regarding the maternal side effects and neonatal outcome will be filled by a part time research assistant.
Statistical Analysis:
Statistical analysis will be performed using the SPSS statistical package. Categoric data like maternal characteristics, the rates of neonatal morbidity and mortality will be compared using Chi square when sample sizes support the approximation. Otherwise, categorical data will be analyzed with two-tailed Fisher exact test if the expected cell frequencies were small. Continuous variables will be compared by Student t test if assumptions of normality and homogeneity of variances appeared to be reasonable. Unpaired variables and differences in distributions will be compared using the Mann-Whitney test. Neonatal outcomes will be analyzed comparing the total number of affected neonates in each group. A p-value <0.05 will be considered statistically significant.
Proposed budget:
Personnel:
A part time research assistant with "BS" background 450,000 L.L./ month x 29 months =13,050,000 L.L.
Tasks expected:
Completing the data sheets:
- F/U on response of mother to tocolysis and assessing maternal side effects
- F/U on the neonates and getting information about the neonatal outcome variables
- Data entry
Medical supplies:
Medications will be provided through the pharmacy.
Compensation for patients:
None.
The total amount of money needed in Lebanese pounds:
13,050,000 L.L./year.
Time frame:
- May 2003 - May 2006 - Collection of data and randomization of patients to the 2 arms of the study
- June 2006 - Sep 2006 - Follow up on patients that were randomized during the first 5 months of 2006 to get information about their pregnancy outcome
- Oct 2006 - Nov 2006 - Data analysis and writing the final paper
Data collection will be under the direct supervision of the principal investigator.
Percent of time spent by principal investigator on this proposal: 20% of research time which accounts for about 20% of time allocated for research activities.
Co-Investigators' Role:
- Dr Usta will help in data analysis and in writing the final paper (5% of research time)
- Dr Mroueh will help in writing the final paper (5% of research time). Two Investigational Drug forms will be used since this trial will involve the same drug nifedipine in 2 different forms Adalat® and Nifedicor®.
Principal Investigator:
Anwar Nassar, MD, Assistant Professor, American University of Beirut Medical Center, Department of Obstetrics and Gynecology
Co-Investigators:
Ihab Usta, MD, Associate Professor, American University of Beirut Medical Center, Department of Obstetrics and Gynecology
Adnan Mroueh, MD, Professor, American University of Beirut Medical Center, Department of Obstetrics and Gynecology
REFERENCES:
Assessment of Risk Factors for Preterm Birth. ACOG practice bulletin, Number 31, October 2001.
Mittendorf R, Dambrosia J, Pryde PG, Lee KS, Gianopoulos JG, Besinger RE, Tomich PG. Association between the use of antenatal magnesium sulfate in preterm labor and adverse health outcomes in infants. Am J Obstet Gynecol;186(6):1111-8. June 2002.
Gyetvai K, Hannah ME, Hodnett ED, Ohlsson A. Tocolytics for preterm labor: a systematic review. Obstet Gynecol;94(5 Pt 2):869-77. Nov 1999.
Mittendorf R, Covert R, Elin R, Pryde PG, Khoshnood B, Lee KS. Umbilical cord serum ionized magnesium level and total pediatric mortality. Obstet Gynecol; 98(1):75-8. July 2001.
Weerakul W, Chittacharoen A, Suthutvoravut S. Nifedipine versus terbutaline in management of preterm labor. Int J Gynaecol Obstet;76(3):311-3. Mar 2002.
Papatsonis DN, Van Geijn HP, Ader HJ, Lange FM, Bleker OP, Dekker GA. Nifedipine and ritodrine in the management of preterm labor: a randomized multicenter trial. Obstet Gynecol;90(2):230-4. Aug 1997.
Larmon JE, Ross BS, May WL, Dickerson GA, Fischer RG, Morrison JC. Oral nicardipine versus intravenous magnesium sulfate for the treatment of preterm labor. Am J Obstet Gynecol;181(6):1432-7. Dec1999.
Koks CA, Brolmann HA, de Kleine MJ, Manger PA. A randomized comparison of nifedipine and ritodrine for suppression of preterm labor. Eur J Obstet Gynecol Reprod Biol;77(2):171-6. Apr 1998.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
-
Beirut, Lebanon
- American University of Beirut Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- All pregnant women diagnosed with preterm labor defined as regular contractions associated with cervical change between 24 and 34 weeks of gestation
Exclusion Criteria:
- Multiple pregnancy
- Preterm rupture of membranes
- Congenital fetal malformations
- IUGR (intra uterine growth restriction)
- Previous tocolysis in this pregnancy
- Chorioamnionitis
- Cervical dilation > 4 cms
- Maternal medical conditions such as renal insufficiency, hepatic insufficiency, or myasthenia gravis
- Non-reassuring fetal heart rate
- Maternal hypotension, defined as a blood pressure < 90/50 mmHg
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Single Group Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: A
High dose Nifedpine arm
|
Arm A: Nifedipine 20 mg sublingual, repeated after 30 minutes if contractions do not decrease in intensity. Maintenance of 120-160 mgs of slow-release nifedipine daily for 48 hours.Once contractions cease, nifedipine will be maintained at 80-120 mg daily in divided doses up to 36 weeks. Arm B: Nifedipine 10 mg sublingual crushed, then 10 mg in 15 min, followed by 10 mg PO Q 15 mins PRN to a maximum of 40 mg in the first hour. Maintenance of 60-80 mgs of slow-release nifedipine daily for 48 hours. Once contractions cease, nifedipine will be maintained at 60 mg daily in divided doses up to 36 weeks.
Other Names:
|
Other: B
Low dose Nifedipine arm
|
Arm A: Nifedipine 20 mg sublingual, repeated after 30 minutes if contractions do not decrease in intensity. Maintenance of 120-160 mgs of slow-release nifedipine daily for 48 hours.Once contractions cease, nifedipine will be maintained at 80-120 mg daily in divided doses up to 36 weeks. Arm B: Nifedipine 10 mg sublingual crushed, then 10 mg in 15 min, followed by 10 mg PO Q 15 mins PRN to a maximum of 40 mg in the first hour. Maintenance of 60-80 mgs of slow-release nifedipine daily for 48 hours. Once contractions cease, nifedipine will be maintained at 60 mg daily in divided doses up to 36 weeks.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Uterine quiescence at 48 hours of initiation of tocolysis
Time Frame: 2 days
|
2 days
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Speed of uterine quiescence, remaining undelivered at >48 hours and >7 days after tocolysis, delivery <34 and 37 weeks of gestation, hours to quiescence, gestational age, maternal drug reactions, hospital stay, neonatal morbidities &neonatal death.
Time Frame: 6 months
|
6 months
|
Collaborators and Investigators
Investigators
- Principal Investigator: Anwar H Nassar, MD, American University of Beirut Medical Center
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pregnancy Complications
- Obstetric Labor Complications
- Obstetric Labor, Premature
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Vasodilator Agents
- Membrane Transport Modulators
- Calcium-Regulating Hormones and Agents
- Reproductive Control Agents
- Calcium Channel Blockers
- Tocolytic Agents
- Nifedipine
Other Study ID Numbers
- OGY.AN.01
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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