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

NCT ID: NCT00549575

Last Updated: 2007-10-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-07-31
• Study Completion Date: 2006-06-30

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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

L ARG

Intervention Type: DRUG

Patients received 14 g/day of L-arginine (90 mL syrup, Veyron France Laboratories).

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

After double blind randomization, patients received a placebo.

Interventions

L ARG

Patients received 14 g/day of L-arginine (90 mL syrup, Veyron France Laboratories).

Intervention Type: DRUG

Placebo

After double blind randomization, patients received a placebo.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Nantes University Hospital

OTHER

Sponsor Role: lead

Principal Investigators

Norbert Winer, Doctor

Role: PRINCIPAL_INVESTIGATOR

Nantes University Hospital

Dominique Darmaun, Professor

Role: STUDY_CHAIR

Nantes University Hospital

Philippe Gilard, Doctor

Role: STUDY_CHAIR

University Hospital, Angers

F Goffinet, Professor

Role: STUDY_CHAIR

Paris-Port-Royal

Locations

Chu-Nantes

Nantes, , France

Countries

France

References

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.

Reference Type: DERIVED

PMID: 19359073 (View on PubMed)

Other Identifiers

99/4-A

Identifier Type: -

Identifier Source: org_study_id