Antepartum Chronic Epidural Therapy (ACET) to Improve Blood Flow to the Uterus, Placenta and Baby in Pre-Eclampsia and Intrauterine Growth Restriction

Phase 3

Completed

• Conditions: Pre-Eclampsia; Fetal Growth Retardation

• Registration Number: NCT00197340
• Lead Sponsor: Hadassah Medical Organization

Brief Summary

Pre-eclampsia (PE) and intrauterine growth restriction (IUGR) are common and important disorders of pregnancy. Both disorders are associated with an impairment of uteroplacental blood flow (UPBF). No effective therapy has been identified to reliably improve UPBF in these patients and typically, obstetric management involves interventional delivery, particularly problematic when remote from term. This study assess the hypothesis that epidural local anesthetics may improve UPBF in these patients.

Detailed Description

Women with sonographic uterine artery flow abnormalities and either PE or IUGR (or both) were randomized to either ACET or non ACET control. Both groups were able to receive standard therapies (in-hospital monitoring, magnesium and anti-hypertensives as appropriate). The first five days of the therapeutic arm (ACET) consisted of a dose-finding trial, where epidural ropivacaine infusions (10ml/hr for 24 hours) of 0•04%, 0•06%, 0•08% and 0•1% and a saline placebo were each administered via tunneled epidural catheters in a randomized, double-blinded, cross-over design over five consecutive days; all three women received all doses. Doppler measurement of flow in the uterine artery was performed at baseline and at the end of each dose period. The ideal dose for an individual was determined to be lowest dose of drug giving maximal effect without side effects; in the second stage of the study, this dose was administered until delivery with the addition of a second placebo day to during this period.

Study Timeline

• Study Start: 2003-08
• Study First Submitted: 2005-09-13
• Study First Submitted QC: 2005-09-13
• Study First Posted: 2005-09-20
• Status Verified: 2006-02
• Primary Completion: 2006-12
• Study Completion: 2006-12
• Last Update Submitted: 2008-07-14
• Last Update Posted: 2008-07-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 20

Inclusion Criteria

• 1. Reliable gestational age based upon an ultrasound crown-rump length performed between 7 to 14 completed weeks gestation. If the ultrasound date matches the date of the last menstrual period (LMP) within 7 days, the LMP date is used, otherwise the ultrasound date is used.

  2. Gestational age at the time of enrollment between 28 to 32 weeks (based upon 1.) and need for in-hospital observation or treatment REGARDLESS of the study.

  3. Presence of uterine artery notching in ultrasound scan. 4. EITHER 4a or 4b (if both, the patient is enrolled as for 4a): 4a. Pre-eclampsia: Women must have criteria #1 and #2 Criterion #1: Hypertension (> 140/90) at rest, measured twice, at least 6 hours apart.

Criterion #2: Proteinuria:

EITHER: At least 0.1 g/l in two random samples at least 6 hours apart. OR: At least 0.3g in a 24 hour collection.

4b Intrauterine growth retardation (IUGR): Women must have criteria #1 and #2. Criterion #1: Ultrasound abdominal circumference below 10th percentile. Criterion #2: Established IUGR for at least 2 weeks.

Exclusion Criteria

• at the time of enrollment: active labor, severe pre-eclampsia, (resting blood pressure ≥ 160mmHg systolic or 110 diastolic, recorded on at least two occasions 6 hours apart), known fetal anomaly, intrauterine infection, placental anomalies (previa, abruption, circumvallate, infarction), twins, and refusal of consent.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Uterine artery blood flow
Gestational age at delivery.

Secondary Outcome Measures

Name	Time	Method
Ductus venosus and MCA blood flow
Proprioceptive loss;
Maternal hemodynamic changes;
Fetal weight (throughout pregnancy and at delivery); amniotic fluid index;
obstetric outcome (maternal mortality, morbidity, neonatal mortality, morbidity, mode of delivery, obstetric complications).

Trial Locations

Locations (1)

Hadassah Hebrew University Medical Center, POB 12000; 🇮🇱 Jerusalem, Israel