L-Arginine Treatment for Severe Vascular Fetal Intrauterine Growth Restriction: a Randomized Double Bind Controlled Trial (L Arginine in IUGR)

Phase 3

Terminated

• Conditions: Intra Uterine Growth Retardation
• Interventions: Drug: L ARG; Drug: Placebo

• Registration Number: NCT00549575
• Lead Sponsor: Nantes University Hospital

Brief Summary

Although there is a strong rationale to supplement gravid patients suffering intrauterine growth restriction (IUGR) or preeclampsia with Arginine or other nitric oxide donors, evidence in the literature has been inconclusive. The current study was designed to determine whether oral treatment with L-Arginine, a nitric oxide (NO) donor, would enhance birth weight and/or decrease neonatal morbidity in pregnancies with severe vascular intrauterine growth restriction (IUGR).

Detailed Description

Patients and Methods: 44 patients with a singleton pregnancy who had been referred for IUGR detected by ultrasonic examination were included. Vascular IUGR was defined by fetal abdominal circumference less than or equal to the third percentile, associated with abnormal uterine Doppler. After double blind randomization, patients received either 14 g/day of L-arginine (90 mL syrup, Veyron France Laboratories), or a placebo. Doppler ultrasound examination of the uterine, umbilical and cerebral circulation, and of ductus venosus was performed prior to inclusion, after 7 days of treatment, and the day before delivery. Ultrasound examination was performed upon randomization, and weekly until birth. Venous blood and urine samples were collected before initiation and after 7 days of treatment, and both maternal and umbilical venous samples were obtained at delivery for nitrate and nitrite (NO2-/ NO3-) determination.

Study Timeline

• Study Start: 2000-07
• Study Completion: 2006-06
• Status Verified: 2007-10
• Study First Submitted: 2007-10-24
• Study First Submitted QC: 2007-10-25
• Last Update Submitted: 2007-10-25
• Study First Posted: 2007-10-26
• Last Update Posted: 2007-10-26

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 44

Inclusion Criteria

• Multicenter randomized trial.
• Patients with a singleton pregnancy with IUGR defined by fetal abdominal circumference less than or equal to the third percentile for gestational age, and abnormal uterine Doppler. Uterine Doppler was considered pathologic if Pourcelot's resistance index (S-D/S) was equal to or higher than 0.7, and/or if an obvious notch was present. If the placenta was not median, the side of the pathologic Doppler had to be on the same side as the placenta

Exclusion Criteria

• Acute fetal distress
• Non vascular and non severe IUGR (normal uterine doppler scans and/or abdominal circumference > 3rd percentile)
• Maternal immune disorder
• IUGR from an infectious etiology
• IUGR associated with fetal malformation, multifetal pregnancy, and preeclampsia upon inclusion

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A	L ARG	Patients received 14 g/day of L-arginine (90 mL syrup, Veyron France Laboratories). Doppler ultrasound examination of the uterine, umbilical and cerebral circulation, and of ductus venous was performed prior to inclusion, after 7 days of treatment, and the day before delivery. Ultrasound examination was performed upon randomization, and weekly until birth. Venous blood and urine samples were collected before initiation and after 7 days of treatment, and both maternal and umbilical venous samples were obtained at delivery for nitrate and nitrite (NO2-/ NO3-) determination.
B	Placebo	After double blind randomization, patients received a placebo. Doppler ultrasound examination of the uterine, umbilical and cerebral circulation, and of ductus venous was performed prior to inclusion, after 7 days of treatment, and the day before delivery. Ultrasound examination was performed upon randomization, and weekly until birth. Venous blood and urine samples were collected before initiation and after 7 days of treatment, and both maternal and umbilical venous samples were obtained at delivery for nitrate and nitrite (NO2-/ NO3-) determination.

Primary Outcome Measures

Name	Time	Method
The principal outcome is birth weight at delivery and neonatal morbidity (Crib Score)	6 weeks

Secondary Outcome Measures

Name	Time	Method
Secondary outcomes are Maternal and fetal hemodynamic with blood pressure and dopplers upon inclusion, after 7 days of treatment and at delivery	6 weeks

Trial Locations

Locations (1)

Chu-Nantes; 🇫🇷 Nantes, France