Back to resultsL-Arginine Treatment for Severe Vascular Fetal Intrauterine Growth Restriction: a Randomized Double Bind Controlled Trial (L Arginine in IUGR)
Primary Purpose
Intra Uterine Growth Retardation
Status
Terminated
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
L ARG
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Intra Uterine Growth Retardation focused on measuring 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
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
Sites / Locations
- Chu-Nantes
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
A
B
Arm 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.
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.
Outcomes
Primary Outcome Measures
The principal outcome is birth weight at delivery and neonatal morbidity (Crib Score)
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
Full Information
NCT ID
NCT00549575
First Posted
October 24, 2007
Last Updated
October 25, 2007
Sponsor
Nantes University Hospital
1. Study Identification
Unique Protocol Identification Number
NCT00549575
Brief Title
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
2. Study Status
Record Verification Date
October 2007
Overall Recruitment Status
Terminated
Why Stopped
terminated
Study Start Date
July 2000 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
June 2006 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Nantes University Hospital
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
44 (Actual)
8. Arms, Groups, and Interventions
Arm Title
A
Arm Type
Experimental
Arm 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.
Arm Title
B
Arm Type
Placebo Comparator
Arm 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.
Intervention Type
Drug
Intervention Name(s)
L ARG
Intervention Description
Patients received 14 g/day of L-arginine (90 mL syrup, Veyron France Laboratories).
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
After double blind randomization, patients received a placebo.
Primary Outcome Measure Information:
Title
The principal outcome is birth weight at delivery and neonatal morbidity (Crib Score)
Time Frame
6 weeks
Secondary Outcome Measure Information:
Title
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
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Norbert Winer, Doctor
Organizational Affiliation
Nantes University Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Dominique Darmaun, Professor
Organizational Affiliation
Nantes University Hospital
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Philippe Gilard, Doctor
Organizational Affiliation
University Hospital, Angers
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
F Goffinet, Professor
Organizational Affiliation
Paris-Port-Royal
Official's Role
Study Chair
Facility Information:
Facility Name
Chu-Nantes
City
Nantes
ZIP/Postal Code
44093
Country
France
12. IPD Sharing Statement
Citations:
PubMed Identifier
19359073
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.
Results Reference
derived
Learn more about this trial
L-Arginine Treatment for Severe Vascular Fetal Intrauterine Growth Restriction: a Randomized Double Bind Controlled Trial (L Arginine in IUGR)
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