Two Dose Regimens of Nifedipine for the Management of Preterm Labor
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|ClinicalTrials.gov Identifier: NCT00137501|
Recruitment Status : Terminated (The trial was terminated because of difficulties in recruitement.)
First Posted : August 30, 2005
Last Update Posted : July 19, 2013
|First Submitted Date ICMJE||August 29, 2005|
|First Posted Date ICMJE||August 30, 2005|
|Last Update Posted Date||July 19, 2013|
|Study Start Date ICMJE||May 2003|
|Actual Primary Completion Date||January 2009 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Uterine quiescence at 48 hours of initiation of tocolysis [ Time Frame: 2 days ]|
|Original Primary Outcome Measures ICMJE
||Delivery > 48 hours from initiation of therapy|
|Current Secondary Outcome Measures ICMJE
||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 ]|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||Two Dose Regimens of Nifedipine for the Management of Preterm Labor|
|Official Title ICMJE||Study of Different Doses of Nifedipine to Treat Preterm Labor|
|Brief Summary||Preterm birth is one of the most important causes of perinatal morbidity and mortality worldwide. Prevention and treatment of preterm labor is important, not as an end in itself, but as a means of reducing adverse events for the neonate. A wide range of tocolytics, drugs used to suppress uterine contractions, have been tried. Magnesium sulfate (MgSO4) is the most widely used tocolytic at the American University of Beirut Medical Center despite the fact that an effective tocolytic role of MgSO4 has never been established. Moreover, the currently available data are suggestive of deleterious fetal effects of MgSO4 in the setting of preterm labor to the extent that some authorities are recommending abandoning it for routine use as a tocolytic therapy. Calcium channel blockers have the ability to inhibit contractility in smooth muscle cells. Consequently, nifedipine has emerged as an effective and rather safe alternative tocolytic agent for the management of preterm labor after several studies have shown that the use of nifedipine in comparison with other tocolytics is associated with a more frequent successful prolongation of pregnancy, resulting in significantly fewer admissions of newborns to the neonatal intensive care unit, and is associated with a lower incidence of respiratory distress syndrome. The unequivocal impact of this method of tocolysis on short term postponement of delivery and the opportunity that this provides for affecting in-utero transfer and steroid administration has prompted many investigators to recommend focusing future trials on testing different dose regimens of nifedipine. To the best of the investigators' knowledge, no study comparing two different dose regimens of nifedipine has been previously published in the literature. The objective of their study is to compare the effectiveness of a high versus a low dose regimen in a total of 200 patients admitted with the diagnosis of preterm labor between 24 and 34 weeks of gestation. In addition, the investigators' study will try to assess the safety profile of the 2 dose regimens on the mother and the neonate by assessing a selected number of outcome variables. The data generated will be used to change their protocol for managing patients presenting with threatened preterm delivery and will fill the existing gap regarding the most effective and safest dose regimen of nifedipine in such patients.|
RESEARCH DESIGN AND METHODS
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:
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.
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:
Side effects associated with nifedipine include a mild decrease in blood pressure and a rise in pulse, headache, flushing, dizziness and nausea.
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 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.
A part time research assistant with "BS" background 450,000 L.L./ month x 29 months =13,050,000 L.L.
Completing the data sheets:
Medications will be provided through the pharmacy.
Compensation for patients:
The total amount of money needed in Lebanese pounds:
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.
Anwar Nassar, MD, Assistant Professor, American University of Beirut Medical Center, Department of Obstetrics and Gynecology
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
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 ICMJE||Interventional|
|Study Phase ICMJE||Phase 3|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
|Condition ICMJE||Labor, Premature|
|Intervention ICMJE||Drug: Nifedipine
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.
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 Name: Adalat, Nifedicor
|Study Arms ICMJE||
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Terminated|
|Actual Enrollment ICMJE
|Original Enrollment ICMJE
|Actual Study Completion Date ICMJE||June 2009|
|Actual Primary Completion Date||January 2009 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages ICMJE||17 Years to 50 Years (Child, Adult)|
|Accepts Healthy Volunteers ICMJE||Yes|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||Lebanon|
|Removed Location Countries|
|NCT Number ICMJE||NCT00137501|
|Other Study ID Numbers ICMJE||OGY.AN.01|
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement ICMJE||Not Provided|
|Responsible Party||Anwar Nassar, American University of Beirut Medical Center|
|Study Sponsor ICMJE||American University of Beirut Medical Center|
|Collaborators ICMJE||Not Provided|
|PRS Account||American University of Beirut Medical Center|
|Verification Date||July 2013|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP