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

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

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).

Study Overview

• Status: Terminated
• Conditions: Intra Uterine Growth Retardation
• Intervention / Treatment: Drug: L ARG; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Nantes, France, 44093
    • Chu-Nantes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; 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.	Drug: L ARG; Patients received 14 g/day of L-arginine (90 mL syrup, Veyron France Laboratories).
Placebo Comparator: B; 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.	Drug: Placebo; After double blind randomization, patients received a placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The principal outcome is birth weight at delivery and neonatal morbidity (Crib Score)	6 weeks

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Nantes University Hospital
• Investigators: Principal Investigator: Norbert Winer, Doctor, CHU Nantes; Study Chair: Dominique DARMAUN, Professor, CHU Nantes; Study Chair: Philippe Gilard, Doctor, University Hospital, Angers; Study Chair: F Goffinet, Professor, Paris-Port-Royal

Publications and helpful links

General Publications

• Winer N, Branger B, Azria E, Tsatsaris V, Philippe HJ, Roze JC, Descamps P, Boog G, Cynober L, Darmaun D. L-Arginine treatment for severe vascular fetal intrauterine growth restriction: a randomized double-bind controlled trial. Clin Nutr. 2009 Jun;28(3):243-8. doi: 10.1016/j.clnu.2009.03.007. Epub 2009 Apr 8.

Study record dates

Study Major Dates

• Study Start: July 1, 2000
• Study Completion (Actual): June 1, 2006

Study Registration Dates

• First Submitted: October 24, 2007
• First Submitted That Met QC Criteria: October 25, 2007
• First Posted (Estimate): October 26, 2007

Study Record Updates

• Last Update Posted (Estimate): October 26, 2007
• Last Update Submitted That Met QC Criteria: October 25, 2007
• Last Verified: October 1, 2007

More Information

Terms related to this study

• Keywords: L-Arginine; Severe Intra uterine growth retardation below the third centile with abnormal uterine doppler; Severe growth retardation with pathologic uterine Doppler; Nitric Oxide Donor
• Additional Relevant MeSH Terms: Pathologic Processes; Fetal Diseases; Pregnancy Complications; Growth Disorders; Fetal Growth Retardation
• Other Study ID Numbers: 99/4-A