Nifedipine Treatment in Preterm Labor

ADMINISTRATION OF NIFIDEPINE VERSUS ATOSIBAN IN PREGNANT WOMEN WITH A THREAT OF PREMATURE LABOR

This is a study for pregnant women who have been diagnosed with Threatened Preterm Labor. The principal aim of this study is to compare the efficacy and safety of Nifedipine treatment versus Atosiban treatment over these patients' newborn babies.

Study Overview

• Status: Withdrawn
• Conditions: Threatened Preterm Labor
• Intervention / Treatment: Drug: Nifedipine; Drug: Atosiban

Detailed Description

Preterm labor is defined as the presence of uterine contractions of sufficient frequency and intensity to effect progressive effacement and dilation of the cervix prior to term gestation (between 20 and 37 weeks).

It is a major health problem of increased incidence, affecting approximately between 7-10% of pregnant women in developed countries with a high socioeconomic costs and high rates of fetal mortality, although perinatal progress.

This study may allow to establish the existence of differences in perinatal outcomes and to define the first choice drug for tocolysis.

• Study Type: Interventional
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

The study population and the inclusion criteria is established by patients between the 24th and 33+6th weeks of pregnancy, fixed by an ecography during the first three-month period, and with a threat of preterm labor (TLP), by the American College of Obstetricians and Gynecologists (ACOG's) criteria:

• Four contractions or more with a duration of at least 30 seconds during 30 minutes

• Documented cervix changes:

  • The cervix changes in a nulliparous woman are: both cervix tact with 0 to 4 cm of dilatation and cervical effacement of at least a 50% (vaginal ultrasound alternative with cervix length two standard curvatures under the average for the gestational age)
  • The cervix changes in a multiparous woman are: 1 to 4 cm of dilatation and cervical effacement of at least a 50% (same ecographic alternative as the nulliparous).
• Patient who had signed the informed consent.

Exclusion Criteria:

Exclusion criteria of the pregnant mother and intrauterine fetal:

• Prior treatment with a different tocolytic from the ones in the protocol.
• Chorioamnionitis.
• Premature rupture of membranes.
• Vaginal Bleeding.
• Major fetal malformations.
• Intrauterine growth retardation (IGR): IGR<percentile 5.
• Cardiopathies (aortic stenosis, congestive heart failure).
• Blood Pressure lower than 100/60 mmHg.
• High transaminase levels.
• Uterine malformations.
• Use of magnesium sulphate.
• Severe hypertensive disorder, defined as blood pressure equal to or greater than 160/100 mmHg or any figure associated with severe preeclampsia.
• Non-reassuring cardiac frequency tracing defined as category II and III of National Institute of Child Health and Human Development (NICHD).
• Asthmatic patients treated with betamimetics.
• Hypertensive patients treated with vasodilators.
• Patient in treatment or treated with another product/s in investigation during the four weeks prior to randomization.
• Hypersensitivity to any drug of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nifedipine; Oral Treatment with Nifedipine capsules (10 mg)Initial dose: 20 mg of nifedipine (2 capsules of 10 mg).Maintenance Dose: 20 mg of nifedipine (2 capsules of 10 mg) every 6 hours.; Maximum Duration of the treatment: 48 hours.	Drug: Nifedipine; Oral Treatment with Nifedipine capsules (10mg)Initial dose: 20 mg of nifedipine (2 capsules of 10 mg).Maintenance Dose: 20 mg of nifedipine (2 capsules of 10 mg) every 6 hours.; Maximum Duration of the treatment: 48 hours.
Active Comparator: Atosiban; Intravenously Treatment with Atosiban (7.5mg/ml)Initial Dose: IV bolus injection during 1 minute + Intravenous infusion 7.5 mg/ml during 3 hours.Maintenance: Maintenance intravenous infusion 7.5 mg/ml at least 18 hours to a maximum of 45 hours.; Maximum Duration of the treatment: 48 hours.	Drug: Atosiban; Intravenously Treatment with Atosiban (7.5mg/ml)Initial Dose: IV bolus injection during 1 minute + Intravenous infusion 7.5 mg/ml during 3 hours.Maintenance: Maintenance intravenous infusion 7.5 mg/ml at least 18 hours to a maximum of 45 hours.; Maximum Duration of the treatment: 48 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neonatal Respiratory Distress Syndrome (RDS) at birth	Clinical assessment: results of the Silverman test. Existence of tachypnea, chest wall retractions, auricular flutter, expiratory grunting and chest-abdominal asynchrony.; Need of 02 at birth (maximum Fi02 in the first 24 hours to estimate the immediate distress). Measurement of pCO2 at birth.; Need of mechanic ventilation: invasive/not invasive and duration of it.; Radiologic estimation of the level of hyaline membrane disease; Need of a surfactant and number of used dosages.	Measured in the newborn at birth and at 30 days after labor

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prolongation of the pregnancy in women with Threatened Preterm Labor	It will be evaluated as a delay in the labor: hours after starting the treatment: more than 48 hours/more than 7 days of prolongation.	more than 48 hours/7 days
Obstetric results	Number of days and type of labor.	at labor and 24 hours after delivery
Presence of the neonatal intracranial hemorrhage	Determination of the appearance and periventricular hemorrhage degree (I-IV) by transfontelar ultrasound scans.	First assessment: in the first week.
Presence of neonatal necrotizing enterocolitis	Monitor the need of canalizing the umbilical vein or artery, the days of parenteral nutrition, days to the start of enteral nutrition, type of enteral nutrition (from the mother, artificial or mixed), start of the elimination of meconium, clinical data from the neonatal necrotizing enterocolitis(abdominal strain, vomiting, blood in the feces, septic appearance) and radiologic/ecographic (dilated bowel loops, intestinal pneumatosis, air in portal, pneumoperitoneum).	at birth and at 30 days after labor
Presence of Retinopathy of prematurity (ROP)	Monitor the iGF1 (Insulin-like growth factor 1) levels on the 3rd week of life as well as an assessing the development of retinopathy.	Between the 4th and 6th week of baby life.
Presence of ductus	Clinical assessment (heart murmur, jumpy pulse, worsening of the clinical basal situation), echocardiography (confirmation of the ductus, Al/Ao relation, ductal size), medical or surgical treatment necessity.	At birth and 30 days after labor
Mother Tolerance Results	Survey to assess the tolerance to the symptomatology induced by the medicines (flush, tachycardia, digestive upsets).	at labor and 24 hours after delivery

Collaborators and Investigators

• Sponsor: Hospital Clinico Universitario de Santiago
• Collaborators: Fundación Ramón Domínguez
• Investigators: Study Chair: Manuel Macía Cortiñas, MD, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain; Principal Investigator: Lourdes González González, MD, Hospital Son Dureta, Mallorca, Spain; Principal Investigator: Javier Martínez Pérez-Mendaña, MD, PhD, Complexo Hospitalario Arquitecto Marcide- Profesor Novoa Santos, Ferrol, Spain; Principal Investigator: José Eloy Moral Santamarina, MD, Complexo Hospitalario de Pontevedra, Pontevedra, Spain; Principal Investigator: Susana Blanco Pérez, MD, Complexo Hospitalario de Ourense; Ourense, Spain; Principal Investigator: Luis Miguel González Seijas, MD, Hospital del Barbanza; Ribeira, A Coruna, Spain; Principal Investigator: Emilio Cabo Silva, MD, Hospital del Salnes; Vilagarcía de Arousa, Pontevedra, Spain

Publications and helpful links

General Publications

• Wilson 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:CD014978. doi: 10.1002/14651858.CD014978.pub2. Review.

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Anticipated): July 1, 2012
• Study Completion (Anticipated): July 1, 2013

Study Registration Dates

• First Submitted: March 14, 2011
• First Submitted That Met QC Criteria: March 14, 2011
• First Posted (Estimate): March 15, 2011

Study Record Updates

• Last Update Posted (Estimate): July 29, 2014
• Last Update Submitted That Met QC Criteria: July 28, 2014
• Last Verified: February 1, 2011

More Information

Terms related to this study

• Keywords: Premature; Nifedipine; Tocolysis; Obstetric Labor
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Premature Birth; Obstetric Labor, Premature; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Membrane Transport Modulators; Hormone Antagonists; Calcium-Regulating Hormones and Agents; Reproductive Control Agents; Calcium Channel Blockers; Tocolytic Agents; Nifedipine; Atosiban
• Other Study ID Numbers: MMC-NIF-2010-01; 2010-024122-37 (EudraCT Number)