Pre-eclampsiaPhase 2/3CITRUPENCT02801695
Evaluation of the Efficacy of Citrulline Supplementation on the Delay of Delivery for Women Hospitalized for Pre-eclampsia (CITRUPE)
A Phase 2/3 study testing Citrulline in people with Pre-eclampsia and Pregnancy, run by Nantes University Hospital at 2 sites in France.
Trial summary
Pre-eclampsia (PE) complicates 2-8 % of pregnancies and is associated with high maternal and fetal morbidity and mortality. The early clinical manifestations are the occurrence of a maternal blood pressure and proteinuria. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Pre-eclampsia, Pregnancy
- What is being tested?
- Citrulline
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 116 participants
- Where
- 2 sitesFrance
- Study dates
- 20 Feb 2017to 1 Dec 2020
- Phase
- Phase 2/3
- 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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- age >= 18 years old
- pregnant woman
- singleton pregnancy
- woman with pre-eclampsia (<36 weeks) without indication of forthcoming extraction
- subjects affiliated with an appropriate social security system
- subjects out of context of guardianship
- written signed informed consent form
Who cannot join
- age < 18 years old
- isolated hypertension or isolated proteinuria
- severe pre-eclampsia with indication of forthcoming extraction in emergency
- term pregnancy >= 36 Weeks when diagnosis is done
- multiple pregnancy
- lactose intolerance
- context of guardianship
Trial locations and contacts
2 sites in 1 country.
France2 sites
CHU de Nantes
Nantes, 44093
Hôpital Cochin (Maternité Port-Royal)
Paris, 75014
About this study
Pre-eclampsia (PE) complicates 2-8 % of pregnancies and is associated with high maternal and fetal morbidity and mortality. The early clinical manifestations are the occurrence of a maternal blood pressure and proteinuria. Placental dysfunction impairs the nutrient supply to the fetus, and may be the cause of an intrauterine growth retardation (IUGR). This is a disease that causes prematurity and currently the only known cure is delivery of the placenta. Nitrogen monoxide (NO) regulates the placental blood flow. However, pre-eclampsia is directly related to a failure of placental NO production. In this context, several clinical trials have tested the effect of NO donors such as L- arginine. However, supplementation with L -Arginine in a randomized trial in Nantes, has proved to be ineffective in severe vascular IUGR.
Citrulline is a natural aminoacid precursor to arginine and in contrast to L-arginine escapes uptake in the liver and appears directly in the peripheral blood converted by the kidney in arginine, released into the systemic circulation, Citrulline may therefore be more effective in the treatment of pre-eclampsia.
This prospective, randomized, comparative and double-blinded study aims to prolong pregnancy for patients with pre-eclampsia before 36 weeks.
- Conditions
- Pre-eclampsia, Pregnancy
- Being tested
- Citrulline, Placebo
- Keywords
- pre-eclampsia, citrulline, pregnancy
- Medical subject headings
- Pre-Eclampsia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CitrullineDrug
Citrulline supplementation
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| L-Citrulline | Experimental | Bolus (9g) after patient stabilization, then 3g 3 times a day until delivery Receives: Drug: Citrulline |
| Lactose | Placebo comparator | Bolus (9g) after patient stabilization, then 3g 3 times a day until delivery Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
number of days between the therapeutic initiation and childbirth
Measured: childbirth
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2016 (estimated)
- Study start20 Feb 2017
- Primary completion1 Dec 2020
- Study completion1 Dec 2020
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 Pre-eclampsiaStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 116 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nantes University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nobert Winer, Dr, Principal investigator, Nantes University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02801695
- Sponsor's protocol ID
- RC15_0475
- Acronym
- CITRUPE
- Status last verified
- Jan 2021
- First submitted
- 3 Jun 2016
- Last updated
- 14 Sep 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Winer N, Misbert E, Masson D, Girault A, Alexandre-Gouabau MC, Ducarme G, Dochez V, Thubert T, Boivin M, Ferchaud-Roucher V, Pere M, Darmaun D. Oral citrulline supplementation in pregnancies with preeclampsia: a multicenter, randomized, double-blind clinical trial. Am J Clin Nutr. 2025 Feb;121(2):488-496. doi: 10.1016/j.ajcnut.2024.12.001. Epub 2024 Dec 9.
PubMed 39638148
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Efficacy of Citrulline Supplementation on the Delay of Delivery for Women Hospitalized for Pre-eclampsia (CITRUPE)
- ClinicalTrials.gov ID
- NCT02801695
- Acronym / sponsor ID
- CITRUPE / RC15_0475
- Conditions
- Pre-eclampsia, Pregnancy
- Keywords
- pre-eclampsia, citrulline, pregnancy
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 116 participants (actual)
- Lead sponsor
- Nantes University HospitalUniversity, hospital or other
- Study start
- 20 Feb 2017 (actual)
- Primary completion
- 1 Dec 2020 (actual)
- Study completion
- 1 Dec 2020 (actual)
- First posted
- 16 Jun 2016 (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.
Pre-eclampsia (PE) complicates 2-8 % of pregnancies and is associated with high maternal and fetal morbidity and mortality. The early clinical manifestations are the occurrence of a maternal blood pressure and proteinuria. Placental dysfunction impairs the nutrient supply to the fetus, and may be the cause of an intrauterine growth retardation (IUGR). This is a disease that causes prematurity and currently the only known cure is delivery of the placenta. Nitrogen monoxide (NO) regulates the placental blood flow. However, pre-eclampsia is directly related to a failure of placental NO production. In this context, several clinical trials have tested the effect of NO donors such as L- arginine. However, supplementation with L -Arginine in a randomized trial in Nantes, has proved to be ineffective in severe vascular IUGR.
Citrulline is a natural aminoacid precursor to arginine and in contrast to L-arginine escapes uptake in the liver and appears directly in the peripheral blood converted by the kidney in arginine, released into the systemic circulation, Citrulline may therefore be more effective in the treatment of pre-eclampsia.
This prospective, randomized, comparative and double-blinded study aims to prolong pregnancy for patients with pre-eclampsia before 36 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| L-Citrulline | Experimental | Drug: CitrullineBolus (9g) after patient stabilization, then 3g 3 times a day until delivery |
| Lactose | Placebo comparator | Drug: PlaceboBolus (9g) after patient stabilization, then 3g 3 times a day until delivery |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- age >= 18 years old
- pregnant woman
- singleton pregnancy
- woman with pre-eclampsia (<36 weeks) without indication of forthcoming extraction
- subjects affiliated with an appropriate social security system
Key exclusion criteria (7 listed)
- age < 18 years old
- isolated hypertension or isolated proteinuria
- severe pre-eclampsia with indication of forthcoming extraction in emergency
- term pregnancy >= 36 Weeks when diagnosis is done
- multiple pregnancy
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 |
|---|---|---|
| CitrullineCitrulline supplementation | Drug | L-Citrulline |
| PlaceboPlacebo | Drug | Lactose |
Primary outcome
number of days between the therapeutic initiation and childbirth
Time frame: childbirth
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2026.
- Results publication: PubMed 39638148Winer N, Misbert E, Masson D, Girault A, Alexandre-Gouabau MC, Ducarme G, Dochez V, Thubert T, Boivin M, Ferchaud-Roucher V, Pere M, Darmaun D. Oral citrulline supplementation in pregnancies with preeclampsia: a multicenter, randomized, double-blind clinical trial. Am J Clin Nutr. 2025 Feb;121(2):488-496. doi: 10.1016/j.ajcnut.2024.12.001. Epub 2024 Dec 9.
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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.
Nobert Winer, Dr principal investigator
Nantes University Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Citrulline in people with Pre-eclampsia and Pregnancy, run by Nantes University Hospital at 2 sites 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 7 inclusion and 7 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: finished, as of the sponsor's last update on 14 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
number of days between the therapeutic initiation and childbirth (time frame: childbirth). 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 NCT02801695, 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 14 Sep 2026.