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

Nantes University Hospital (NUH)

Status and phase: Terminated; Phase 3

Conditions: Intra Uterine Growth Retardation

Treatments: Drug: L ARG; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT00549575

99/4-A

Details and patient eligibility

About

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).

Full 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.

Enrollment: 44 patients

Sex: Female

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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44 participants in 2 patient groups, including a placebo group

A

Experimental group

Description:

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.

Treatment:

Drug: L ARG

B

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo