Gestational Diabetes: Induction Versus Expectant Management of Labour (GINEXMAL)

GINEXMAL RCT: Induction of Labour Versus Expectant Management in Gestational Diabetes Pregnancies

The purpose of this study is to determine whether, in Gestational Diabetes Mellitus (GDM) pregnancies, induction of labour at 38-39 weeks of pregnancy is superior to expectant management in terms of maternal and neonatal outcomes.

Study Overview

• Status: Completed
• Conditions: Gestational Diabetes; Gestational Diabetes Mellitus; Pregnancy-Induced Diabetes; Diabetes Mellitus, Gestational; Diabetes, Pregnancy Induced
• Intervention / Treatment: Other: INDUCTION of LABOUR

Detailed Description

Gestational Diabetes Mellitus (GDM) is one of the most common complications of pregnancy and its incidence is estimated as around 7%. Babies born from women with GDM are significantly more exposed to perinatal risk. Furthermore in GDM pregnancies an increased C-section rate has been observed, mostly unjustified.

Strong evidence, based on prospective studies and randomized controlled trials, in favour or against the effectiveness and safeness of induction in women with GDM, are missing. The aim of the present study is to identify the best management for these women at term and provide evidence that could change the current clinical practice.

To reach this objective, 1760 eligible women will be recruited at 9 Teaching Hospitals (5 in Italy, 4 all over the world). Sample size has been estimated to demonstrate a difference between the two arms ≥ 6% (31% of C-section in the expectant group and 25% in the induction group; relative difference between the 2 groups equal to 20% in favor of induction; Kjos et al, 1993), considering an α error equal to 5% and 80% power.

Patients will be randomized to induction of labour (N=880) or expectant management (N=880). Data on maternal and neonatal outcomes will be collected at delivery and until maternal and neonatal discharge.

• Study Type: Interventional
• Enrollment (Actual): 425
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Petah-Tiqva, Israel, 49100
    • Helen Schneider's Hospital for Women - Rabin Medical Center
• Italy
  • Brescia, Italy, 25100
    • I Ostetricia Spedali Civili
  • Florence, Italy, 50141
    • Department of Gynecology Perinatology and Human Reproduction
  • Milan, Italy, 20154
    • Unità Operativa di Ostetricia e Ginecologia - Ospedale Buzzi
  • Trieste, Italy, 34100
    • Institute for Maternal and Child Health - IRCCS Burlo Garofolo
  • Turin, Italy, 10126
    • Dipartimento di Discipline Ginecologiche ed Ostetriche - Università di Torino
• Netherlands
  • Utrecht, Netherlands, 3508 AB
    • Division Woman and Baby - UMC Utrecht/ Wilhelmina Children's Hospital
• Slovenia
  • Ljubljana, Slovenia, SI-1000
    • Department of ob/gyn, Division of perinatology - University Medical Centre
• Sri Lanka
  • Colombo, Sri Lanka, Colombo 08
    • Department of Obstetrics and Gynecology - University of Colombo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Maternal age > 18;
• Singleton pregnancy in vertex presentation;
• Gestational age between 38-39 weeks verified by LMP and first trimester ultrasound when available;
• Women diagnosed with GDM in the current pregnancy [Diagnosis will be based upon abnormal 50 Gr. GCT (>140) followed by >2 abnormal indices in the OGTT (according to C&C criteria). Women with GCT>200 mg/dl will undergo 100 gr OGTT as well];
• No other contraindications for vaginal delivery.

Exclusion Criteria:

• Pre-gestational diabetes;
• Prior C-section;
• Suspected estimated fetal weight> 4000 gr. at enrollment;
• Any known contraindications for vaginal delivery;
• Uncertain gestational age;
• Non-reassuring fetal status necessitating immediate obstetrical intervention (prompt delivery/prompt C-section);
• Maternal disease complicating pregnancy and necessitating delivery (e.g Severe PET);
• Bishop score >7 at enrollment;
• Major fetal malformation.

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: INDUCTION of LABOUR; At enrollment patients assigned to the induction group will be admitted to the obstetric ward and will undergo induction of labour as described in the intervention section. Once patient's Bishop score exceeds 7 or regular contractions are diagnosed, patients will be transferred to the delivery ward for artificial rupture of membranes (ARM) or Oxytocin augmentation as indicated.	Other: INDUCTION of LABOUR; Induction of labour will be performed by using dinoprostone 2 mg vaginally or dinoprostone 0.5 mg intracervically at 6-8h interval (up to 5 doses) or dinoprostone 10 mg vaginal device. Patients, in which cervical ripening does not occur (Bishop score < 7) after 5 attempts with PGE2, will be offered either oxytocin or Foley catheter induction or C-section, according to local protocols.
NO_INTERVENTION: EXPECTANT MANAGEMENT; Patients enrolled in the conservative management arm will be followed up twice weekly for foetal wellbeing by Non-stress test and Biophysical profile. Patients will be followed up to 41+0 weeks. Patients, who will not deliver by this gestational age, will be admitted for labour induction (see the above protocol). Induction of labour will be offered when non-reassuring foetal status is suspected. All patients in the conservative arm will undergo foetal weight ultrasound estimation prior to induction. Patients with estimated foetal weight over 4000 gr will be offered a C-section.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
C-section rate	1 minute after delivery

Secondary Outcome Measures

Outcome Measure	Time Frame
Operative Vaginal Delivery	1 minute after delivery
Perineal Tears or Episiotomy	1 minute after delivery
Postpartum haemorrhage	within 24 hours from delivery
Maternal Blood Transfusion	until maternal discharge
Maternal Intensive Care Unit Admission	until maternal discharge
Neonatal Weight	10 minutes after delivery
Neonatal Apgar score at 1', 5', 10' minutes	1, 5, 10 minutes after delivery
Shoulder Dystocia	during delivery
Manoeuvres for Shoulder Dystocia	during delivery
Neonatal Intensive Care Unit Admission	until neonatal discharge
Arterial cord Ph inferior to 7.2	within 5 minutes from delivery
Neonatal Hyperbilirubinemia	until neonatal discharge
Clinical and Biochemical Neonatal Hypoglycemia	until neonatal discharge
Neonatal Polycythemia	until neonatal discharge
Neonatal Birth Trauma	10 minute from delivery or until neonatal discharge
Neonatal Respiratory Distress/Transient Tachypnea	until neonatal discharge
Neonatal Need for Respiratory Support	until neonatal discharge
Maternal death	until neonatal discharge
Perinatal Death	until neonatal discharge
Spontaneous/Instrumental third stage of labour	within 1 hours from delivery
Indication for Cesarean Section	1 minutes after delivery

Collaborators and Investigators

• Sponsor: IRCCS Burlo Garofolo
• Investigators: Study Director: Salvatore Alberico, MD, Institute for Maternal and Child Health IRCCS Burlo Garofolo; Study Director: Moshe Hod, MD, Helen Schneider's Hospital for Women - Rabin Medical Center

Publications and helpful links

General Publications

• Maso G, Alberico S, Wiesenfeld U, Ronfani L, Erenbourg A, Hadar E, Yogev Y, Hod M; GINEXMAL Study Cooperative Research Group. "GINEXMAL RCT: Induction of labour versus expectant management in gestational diabetes pregnancies". BMC Pregnancy Childbirth. 2011 Apr 20;11:31. doi: 10.1186/1471-2393-11-31.

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (ACTUAL): March 1, 2014
• Study Completion (ACTUAL): March 1, 2014

Study Registration Dates

• First Submitted: January 26, 2010
• First Submitted That Met QC Criteria: January 28, 2010
• First Posted (ESTIMATE): January 29, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): April 30, 2015
• Last Update Submitted That Met QC Criteria: April 29, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Neonatal Outcomes; Maternal Outcomes; Induced Labour; Expectant Management; C-section rate
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Pregnancy Complications; Diabetes Mellitus; Diabetes, Gestational
• Other Study ID Numbers: RC 22/09