Intra Uterine Growth RetardationPhase 3NCT00549575
L-Arginine Treatment for Severe Vascular Fetal Intrauterine Growth Restriction: a Randomized Double Bind Controlled Trial (L Arginine in IUGR)
A Phase 3 study testing L ARG in people with Intra Uterine Growth Retardation, run by Nantes University Hospital at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 years, women only
- Conditions the study is for
- Intra Uterine Growth Retardation
- What is being tested?
- L ARG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 1 siteFrance
- Study dates
- Jul 2000to Jun 2006
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
1 site in 1 country.
About this study
Official title: L-Arginine Treatment for Severe Vascular Fetal Intrauterine Growth Restriction: a Randomized Double Bind Controlled Trial
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).
Read the 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
- Being tested
- L ARG, Placebo
- 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
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L ARGDrug
Patients received 14 g/day of L-arginine (90 mL syrup, Veyron France Laboratories).
PlaceboDrug
After double blind randomization, patients received a placebo.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: L ARG |
| 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The principal outcome is birth weight at delivery and neonatal morbidity (Crib Score)
Measured: 6 weeks
Secondary outcomes (1)
Secondary outcomes are Maternal and fetal hemodynamic with blood pressure and dopplers upon inclusion, after 7 days of treatment and at delivery
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2007 (estimated)
- Study startJul 2000
- Study completionJun 2006
Why it stopped: terminated
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Intra Uterine Growth RetardationStudies of the same condition, open and under way.
- More trials run by Nantes University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nantes University Hospital
- Sponsor type
- University, hospital or other
- Investigators
- Norbert Winer, Doctor, Principal investigator, Nantes University HospitalDominique Darmaun, Professor, Study chair, Nantes University HospitalPhilippe Gilard, Doctor, Study chair, University Hospital, AngersF Goffinet, Professor, Study chair, Paris-Port-Royal
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00549575
- Sponsor's protocol ID
- 99/4-A
- Status last verified
- Oct 2007
- First submitted
- 24 Oct 2007
- Last updated
- 26 Oct 2007
- Results posted
- No
Publications
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.
PubMed 19359073
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- L-Arginine Treatment for Severe Vascular Fetal Intrauterine Growth Restriction: a Randomized Double Bind Controlled Trial
- ClinicalTrials.gov ID
- NCT00549575
- Acronym / sponsor ID
- 99/4-A
- 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
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: terminated
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Nantes University HospitalUniversity, hospital or other
- Study start
- Jul 2000
- Study completion
- Jun 2006 (actual)
- First posted
- 26 Oct 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: L ARGPatients 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. |
| B | Placebo comparator | Drug: PlaceboAfter 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. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| L ARGPatients received 14 g/day of L-arginine (90 mL syrup, Veyron France Laboratories). | Drug | A |
| PlaceboAfter double blind randomization, patients received a placebo. | Drug | B |
Primary outcome
The principal outcome is birth weight at delivery and neonatal morbidity (Crib Score)
Time frame: 6 weeks
1 secondary outcome
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
Results and safety
The study was stopped early (reason given: terminated). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2007.
- Derived from this study: PubMed 19359073Winer 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Norbert Winer, Doctor principal investigator
Nantes University Hospital
Dominique Darmaun, Professor study chair
Nantes University Hospital
Philippe Gilard, Doctor study chair
University Hospital, Angers
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing L ARG in people with Intra Uterine Growth Retardation, run by Nantes University Hospital at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Oct 2007. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: terminated). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The principal outcome is birth weight at delivery and neonatal morbidity (Crib Score) (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00549575, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2007.