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

Sponsored by:	Nantes University Hospital
Information provided by:	Nantes University Hospital
ClinicalTrials.gov Identifier:	NCT00549575

Purpose

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).

Condition	Intervention	Phase
Intra Uterine Growth Retardation	Drug: L ARG Drug: Placebo	Phase III

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	L-Arginine Treatment for Severe Vascular Fetal Intrauterine Growth Restriction: a Randomized Double Bind Controlled Trial

Resource links provided by NLM:

Drug Information available for: Arginine Arginine hydrochloride

U.S. FDA Resources

Further study details as provided by Nantes University Hospital:

Primary Outcome Measures:

The principal outcome is birth weight at delivery and neonatal morbidity (Crib Score) [ Time Frame: 6 weeks ]

Secondary Outcome Measures:

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

Enrollment:	44
Study Start Date:	July 2000
Study Completion Date:	June 2006

Arms	Assigned Interventions
A: Experimental 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).
B: Placebo Comparator 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.

Arms

Assigned Interventions

A: Experimental

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).

B: Placebo Comparator

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.

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

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00549575

Locations

France
CHU-NANTES
NANTES, France, 44093

Sponsors and Collaborators

Nantes University Hospital

Investigators

Principal Investigator:	Norbert Winer, Doctor	CHU NANTES
Study Chair:	Dominique Darmaun, Professor	CHU NANTES
Study Chair:	Philippe Gilard, Doctor	CHU ANGERS
Study Chair:	F Goffinet, Professor	Paris-Port-Royal

More Information

No publications provided by Nantes University Hospital

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

Winer N, Branger B, Azria E, Tsatsaris V, Philippe HJ, Rozé 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. Epub 2009 Apr 8.

Study ID Numbers:	99/4-A
Study First Received:	October 24, 2007
Last Updated:	October 25, 2007
ClinicalTrials.gov Identifier:	NCT00549575 History of Changes
Health Authority:	France: Afssaps - French Health Products Safety Agency

Keywords provided by Nantes University Hospital:

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
Severe Intra uterine growth retardation below the third centile with abnormal uterine doppler

Study placed in the following topic categories:

Nitric Oxide
Fetal Diseases
Pregnancy Complications
Arginine

Growth Disorders
Fetal Growth Retardation
Nitric Oxide Donors

Additional relevant MeSH terms:

Fetal Diseases
Pathologic Processes
Pregnancy Complications
Growth Disorders
Fetal Growth Retardation

ClinicalTrials.gov processed this record on September 10, 2009