Treatment of restriction in fetal growth with L-arginine
| ISRCTN | ISRCTN32082979 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN32082979 |
| Secondary identifying numbers | 2017-4-14-HCUVA |
- Submission date
- 26/01/2018
- Registration date
- 12/03/2018
- Last edited
- 06/11/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Pregnancy and Childbirth
Plain English summary of protocol
Background and study aims
Intrauterine growth restriction (IUGR) is a condition in which an unborn baby is smaller than it should be because it is not growing at a normal rate inside the womb. Children with IUGR have a higher risk of perinatal mortality, infant mortality, sudden infant death syndrome, cerebral palsy, and alterations in cognitive development and physical growth. The aim of this study is to find out whether giving an L-arginine supplement to pregnant women with IUGR decreases the risk of the newborn being diagnosed as being small for gestational age and the perinatal morbidity and mortality associated with this problem.
Who can participate?
Pregnant women between 24 and 32 weeks of gestation, with a single fetus with IUGR
What does the study involve?
Participants are randomly allocated to one of two groups to take either one packet a day of L-arginine or a placebo (dummy) supplement until the time of delivery. Outcomes are measured including birth weight, perinatal morbidity, perinatal mortality, preterm delivery, and admission to the neonatal intensive care unit (NICU).
What are the possible benefits and risks of participating?
L-arginine may reduce the risks of IUGR. Although it has no serious side effects, nausea, diarrhea and weakness have been reported with excessive consumption of this substance.
Where is the study run from?
Hospital Clínico Universitario Virgen de la Arrixaca (Spain)
When is the study starting and how long is it expected to run for?
January 2015 to June 2024
Who is funding the study?
Fundación para Formación e Investigación Sanitaria (Spain)
Who is the main contact?
Catalina De Paco Matallana
katy.depaco@gmail.com
Contact information
Public
Unidad Materno Fetal-Hospital Maternal
Hospital Clínico Universitario Virgen de la Arrixaca
Cta. Madrid-Cartagena s/n 30120
El Palmar - Murcia
30120
Spain
| Phone | +34 (0)968395588 |
|---|---|
| katy.depaco@gmail.com |
Study information
| Study design | Single-centre double-blind placebo-controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Treatment of restriction in fetal growth with L-arginine: randomized clinical trial, double-blind, controlled with placebo |
| Study acronym | ARCIR |
| Study objectives | To assess whether oral administration of L-arginine in pregnant women with IUGR decreases the risk of newborn diagnosed as being small for gestational age and the perinatal morbidity and mortality associated with this problem. |
| Ethics approval(s) | 1. Approved 30/03/2015, Comité Ético de la Región de Murcia (Carretera Madrid-Cartagena S/N, El Palmar (Murcia), 30120, Spain; +34 968 369031; rosariogarcia7@carm.es), ref: 2017-4-14-HCUVA 2. Approved 24/04/2017, Ethics Committee H.C.U. Virgen de la Arrixaca, ref: 2017-4-14-HCUVA |
| Health condition(s) or problem(s) studied | Intrauterine growth restriction (IUGR) |
| Intervention | Pregnant women with an ultrasonographic diagnosis of IUGR will be invited to participate in the study. After signing informed consent, women will be randomised and assigned to one of two study groups: 1. Women in the L-arginine group will take 1 packet/day containing 7.84 gram of L-arginine 2. The placebo group will take 1 packet/day, identical in weight, size, color and flavor to those of L-Arginine but that will only contain excipient without pharmacological activity (96% corn starch) Women will be instructed to take the packet at least one hour before breakfast in order not to interfere with the absorption of other constituents of the diet. The maximum treatment duration will be 20 weeks and the follow-up will be done every week. |
| Intervention type | Supplement |
| Primary outcome measure | Birth weight below the 10th percentile for gestational age and sex, according to local reference curves. The estimation of fetal weight is made by combining the cephalic perimeter, abdominal perimeter and femur length. This weight estimation is usually done every two weeks when the estimated fetal weight percentile is between the 3rd and 10th percentile and each week when it is below the 3th percentile. |
| Secondary outcome measures | Secondary objectives will be analyzed at the postnatal level, except for the diagnosis of the development of hypertension in pregnancy, either preeclampsia or gestational hypertension: 1. Birth weight 2. Gestational age at birth 3. Size of the newborn 4. Abdominal perimeter of the newborn 5. Cephalic perimeter of the newborn 6. Weight index of the newborn 7. Placental weight 8. Placental weight/weight ratio of the newborn 9. Low weight (<2500 g) 10. Very low weight (<1500 g) 11. Preterm delivery <37 weeks of gestation 12. Preterm delivery <32 weeks gestation 13. Preterm delivery <28 weeks gestation 14. Apgar score at minute 1 and 5 15. Perinatal mortality (early fetal and neonatal mortality) 16. Respiratory distress syndrome 17. Bronchopulmonary dysplasia 18. Intraventricular hemorrhage 19. Periventricular leukomalacia (selene) 20. Neonatal sepsis 21. Necrotizing enterocolitis 22. Retinopathy of prematurity 23. Compound of perinatal morbi-mortality 24. Admission to the neonatal intensive care unit 25. Congenital malformations 26. Induction of labor 27. Cesarean section 28. Preeclampsia 29. Gestational hypertension 30. Antepartum hemorrhage 31. Postpartum hemorrhage 32. Maternal infection 33. Need for maternal hospitalization 34. Maternal adverse effects |
| Overall study start date | 01/01/2015 |
| Completion date | 01/06/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Female |
| Target number of participants | 130 |
| Total final enrolment | 73 |
| Key inclusion criteria | 1. Age ≥18 years 2. Single pregnancy 3. Ultrasonographic diagnosis of IUGR: estimated fetal weight lower than the 10th percentile for gestational age according to local or national reference values, independently of the results of the Doppler parameters of the umbilical, middle cerebral and/or uterine arteries 4. Live fetuses at 11 and 13 at weeks gestation 6. Gestational age between 24 and 32 weeks 7. No indication of imminent or planned birth 8. Availability to participate in the study and sign the consent |
| Key exclusion criteria | 1. Women with medical complications such as preeclampsia, chronic hypertension, kidney disease, diabetes mellitus, liver dysfunction, autoimmune disease or other significant medical complications 2. Women with a history of major mental disorders (schizophrenia, manic-depressive illness) 3. Women in labor or with imminent or planned delivery 4. Fetal malformation 5. Acute fetal distress 6. IUGR associated with infectious disease 7. Multiple pregnancy |
| Date of first enrolment | 05/02/2018 |
| Date of final enrolment | 23/01/2024 |
Locations
Countries of recruitment
- Spain
Study participating centre
30008
Spain
Sponsor information
Research organisation
Calle Luis Fontes Pagan, 9, Murcia
Murcia
30003
Spain
| Phone | +34 (0)968 35 97 67 |
|---|---|
| lola.serna@carm.es | |
| Website | https://www.ffis.es |
"ROR" |
https://ror.org/05m5has32 |
Funders
Funder type
Research organisation
No information available
Results and Publications
| Intention to publish date | 01/12/2021 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Throughout 2019 and 2020 the statistical analysis of the results will be carried out, followed by publications. |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date. |
Editorial Notes
06/11/2024: The following changes were made to the study record:
1. The recruitment end date was changed from 01/12/2019 to 23/01/2024.
2. The overall study end date was changed from 01/12/2020 to 01/06/2024.
3. Total final enrolment number added.
04/11/2024: Ethics approval details added.
22/11/2018: The recruitment end date was changed from 01/10/2018 to 01/12/2019.
