Clinical trial NCT00549575: L-Arginine Treatment for Severe Vascular Fetal Intrauterine Growth Restriction: a Randomized Double Bind Controlled Trial (L Arginine in IUGR)
Official title: L-Arginine Treatment for Severe Vascular Fetal Intrauterine Growth Restriction: a Randomized Double Bind Controlled Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Intra Uterine Growth Retardation
Keywords: Severe Intra uterine growth retardation below the third centile with abnormal uterine doppler
Severe growth retardation with pathologic uterine Doppler
L-Arginine
Nitric Oxide Donor
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2007-10-26
Enrollment: 44
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: The principal outcome is birth weight at delivery and neonatal morbidity (Crib Score)
timeFrame: 6 weeks
Secondary outcomes:
measure: Secondary outcomes are Maternal and fetal hemodynamic with blood pressure and dopplers upon inclusion, after 7 days of treatment and at delivery
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Nantes
country: France
facility: Chu-Nantes
Study officials:
affiliation: Nantes University Hospital
name: Norbert Winer, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Nantes University Hospital
name: Dominique Darmaun, Professor
role: STUDY_CHAIR
affiliation: University Hospital, Angers
name: Philippe Gilard, Doctor
role: STUDY_CHAIR
affiliation: Paris-Port-Royal
name: F Goffinet, Professor
role: STUDY_CHAIR
References:
citation: 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.