Brain InjuriesPhase 3NIPANCT05008926
The NIPA Study Naloxegol Administration to Prevent Opioids Induced Gastrointestinal Motility Disturbance in Brain Injured PAtients
A Phase 3 study testing Naloxegol in people with Brain Injuries, run by University Hospital, Brest at 10 sites in France.
Trial summary
Impaired gastrointestinal transit (IGT) especially constipation, is common among patients under mechanical ventilation, occurring in up to 80 % of the patients during the first week, and has been associated with worse outcome in intensive care unit (ICU). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Injuries
- What is being tested?
- Naloxegol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 370 participants
- Where
- 10 sitesFrance
- Study dates
- 15 Mar 2022to 26 Apr 2028
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ to 18 years old
- Admission to intensive care unit for traumatic brain injury or subarachnoid hemorrhage without other life-threatening injury
- Patients under sedation with administration of opiate-agonists, μ receptor agonists (Sufentanil, Fentanyl, Remifentanil, Morphine) for less than 24 hours
- Expected duration of invasive mechanical ventilation and sedation of 48 hours or more
- Intracranial pressure monitoring
- Enteral feeding by oro / nasogastric tube
- Affiliated or beneficiary of the French social security system
Who cannot join
- Patient who received opioids for more than 24 hours
- Patient with refractory intracranial hypertension at the time of inclusion: intracranial hypertension requiring therapy other than analgo-sedation (thiopental, targeted temperature management, decompressive craniectomy)
- Acute or chronic renal failure with creatinine clearance <60ml / min
- Known or suspected acute gastrointestinal obstruction
- Risk of digestive perforation:
- history of peptic ulcer
Show all 23Show fewer
- Crohn's disease
- Ogilvie syndrome
- acute diverticulitis
- infiltrating gastrointestinal tumor
- recurrent or advanced ovarian cancer
- peritoneal metastasis
- recent abdominal trauma with risk of digestive perforation
- Concomitant treatment with a strong or moderate inhibitory effect of CYP 3A4 (For example: clarithromycin, ketaconazole, itraconazole, telithromycin, ritonavir, indinavir, saquinavir) or with a strong inducing effect (carbamazepin, rifampicin, millepertuis)
- Concomitant treatment with vascular endothelial growth factor (VEGF) inhibitor
- Allergy to Naloxegol or one of its excipients
- Recent history of myocardial infarction within the past 6 months, symptomatic congestive cardiovascular disease, QT ≥ 500 msec
- Patient with a medical decision for rapid palliative care
- Pregnancy and / or breastfeeding
- Child Pugh C stage cirrhosis
- Patient under legal protection or deprived of liberty
- Patient with another life-threatening injury
- History of clinically important alterations of the blood-brain barrier: primary brain tumors, metastasis or other inflammatory pathologies in the CNS, active multiple sclerosis, Alzheimer's disease at an advanced stage.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
France10 sites
CHU de Bordeaux - Réanimation chirurgicale
Bordeaux, France, 33000
CHU Bordeaux
Bordeaux, 33000
CHU Brest
Brest, 29609
CHU de Lille
Lille, 59000
CHU de Montpellier
Montpellier, 34295
CHU Nantes
Nantes, 44093
Hôpital La Pitié Salpétrière (APHP)
Paris, 75013
CHU de Strasbourg
Strasbourg, 67098
CHU Tours - Hôpital BRETONNEAU
Tours, 37000
CHU Tours - Hôpital TROUSSEAU
Tours, 37170
About this study
Official title: The NIPA Study: A Randomized Double-blind Control Clinical Trial Naloxegol Administration to Prevent Opioids Induced Gastrointestinal Motility Disturbance in Brain Injured PAtients
Impaired gastrointestinal transit (IGT) especially constipation, is common among patients under mechanical ventilation, occurring in up to 80 % of the patients during the first week, and has been associated with worse outcome in intensive care unit (ICU). Although IGT in critically ill patients is multifactorial and some components are due to complex disease, there is increasing evidence that exogenous opioids contribute to bowel dysmotility.
Sedatives and especially opioids are largely used in the brain injured population to control intracranial pression, reduce metabolic rate, manage or prevent seizures, and improve mechanical ventilator synchrony. Therefore, brain injured patients are particularly at risk to develop IGT. The occurrence of IGT is associated with adverse outcomes in intensive care unit. Both gastric reflux and impaired peristaltic contractions are associated with ventilator-acquired pneumonia.
Read more
The actual challenge is to prevent motility disorders before it occurs. A preventive strategy could in turn reduce the occurrence of complications related to impaired gastrointestinal transit such as ventilator-acquired pneumonia, bacteremia etc. It could also reduce the complications of feed intolerance and thus reduce morbidity and mortality in ICU.
Naloxegol is a polyethylene glycol derivative of naloxol, which is a derivative of naloxone and a peripherally acting µ-opioid receptor antagonist. Contrary to naloxone, naloxegol has a very low penetration into the central nervous system, therefore it could be a relevant option for ileus prevention without the risk of impaired sedation.
The aim of our study is to assess the efficacy of the administration of naloxegol on the onset of early constipation and early ventilator-acquired pneumonia in brain injured patients receiving opioids for analgosedation.
Read the detailed description
Multicenter, randomized, double-blind, placebo-controlled experimental study of Naloxegol.
- Conditions
- Brain Injuries
- Being tested
- Naloxegol, Placebo
- Keywords
- Impaired gastrointestinal transit, Subarachnoid Hemorrhage, Traumatic brain injury
- Medical subject headings
- Brain Injuries, Subarachnoid Hemorrhage, Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NaloxegolDrug
Administration of Naloxegol 25 mg per day by nasogastric tube (SNG) or orogastric tube (SOG). The administration should be started within the first 24 hours after the patient is admitted to intensive care and continued for the duration of the administration of the morphine derivative and until 48 hours after its discontinuation.
PlaceboDrug
Administration of the placebo according to the same procedures as the experimental arm.
| Study group | Role | What they receive |
|---|---|---|
| Naloxegol | Experimental | Administration of Naloxegol 25 mg per day by nasogastric tube (NG) or orogastric tube (OG). The administration should be started within the first 24 hours after the patient is admitted to intensive care unit and continued for the duration of the administration of the morphine derivative and until 48 hours after its discontinuation.
Management of constipation and gastroparesis according to the recommendations. Receives: Drug: Naloxegol |
| Placebo | Placebo comparator | Administration of the placebo according to the same procedures as the experimental arm. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of bowel movement
Measured: 6 days
Incidence of ventilator-acquired pneumonia
Measured: 7 days
Secondary outcomes (9)
Proportion of patient-days who received the daily calorie goal (25 Kcal / kg / day)
Measured: 10 days
Number of patients who required one or more administration of erythromycin and / or metoclopramide for vomiting occurring during enteral feeding
Measured: 10 days
Number of patients who received one or more rectal laxative for constipation
Measured: 10 days
Time in days of occurrence of the first bowel movement (in case of late constipation)
Measured: 10 days
Number of patients with ventilator-acquired pneumonia after D7 of invasive mechanical ventilationventilation (after D7 of invasive mechanical ventilation)
Measured: 10 days
Number of days without invasive mechanical ventilation
Measured: 10 days
Duration of hospitalization in intensive care unit
Measured: 10 days
Glasgow Outcome Scale Extended Score
The Glasgow Outcome Scale (GOS) is a comprehensive assessment scale for functional outcome that classifies a patient's condition into one of five categories: Death, Vegetative State, Severe Handicap, Moderate Handicap or Good Recovery. The extended GOS scale (GOSE) allows a more detailed classification into eight categories, thanks to a subdivision into two levels (lower and higher) of the categories "severe handicap", "moderate handicap" and "good recovery"
Measured: 6 month
Number of patients who experienced an episode of intracranial hypertension requiring targeted temperature management, barbiturates, or decompression craniectomy.
Measured: 10 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2021
- Study start15 Mar 2022
- Primary completion26 Oct 2027 (estimated)
- Study completion26 Apr 2028 (estimated)
Why it stopped: interim analysis - Results ongoing
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain InjuriesStudies of the same condition, open and under way.
- More trials run by University Hospital, BrestThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 370 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Brest
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Olivier Huet, PU-PH, Principal investigator, CHU Brest
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05008926
- Sponsor's protocol ID
- 29BRC18.0262 (NIPA)
- Acronym
- NIPA
- Status last verified
- Jun 2026
- First submitted
- 10 Aug 2021
- Last updated
- 16 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All collected data that underlie results in a publication
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The NIPA Study: A Randomized Double-blind Control Clinical Trial Naloxegol Administration to Prevent Opioids Induced Gastrointestinal Motility Disturbance in Brain Injured PAtients
- ClinicalTrials.gov ID
- NCT05008926
- Acronym / sponsor ID
- NIPA / 29BRC18.0262 (NIPA)
- Conditions
- Brain Injuries
- Keywords
- Impaired gastrointestinal transit, Subarachnoid Hemorrhage, Traumatic brain injury
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: interim analysis - Results ongoing
- Enrolment
- 370 participants (estimated)
- Lead sponsor
- University Hospital, BrestUniversity, hospital or other
- Study start
- 15 Mar 2022 (actual)
- Primary completion
- 26 Oct 2027 (estimated)
- Study completion
- 26 Apr 2028 (estimated)
- First posted
- 17 Aug 2021 (actual)
- 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.
Impaired gastrointestinal transit (IGT) especially constipation, is common among patients under mechanical ventilation, occurring in up to 80 % of the patients during the first week, and has been associated with worse outcome in intensive care unit (ICU). Although IGT in critically ill patients is multifactorial and some components are due to complex disease, there is increasing evidence that exogenous opioids contribute to bowel dysmotility.
Sedatives and especially opioids are largely used in the brain injured population to control intracranial pression, reduce metabolic rate, manage or prevent seizures, and improve mechanical ventilator synchrony. Therefore, brain injured patients are particularly at risk to develop IGT. The occurrence of IGT is associated with adverse outcomes in intensive care unit. Both gastric reflux and impaired peristaltic contractions are associated with ventilator-acquired pneumonia.
The actual challenge is to prevent motility disorders before it occurs. A preventive strategy could in turn reduce the occurrence of complications related to impaired gastrointestinal transit such as ventilator-acquired pneumonia, bacteremia etc. It could also reduce the complications of feed intolerance and thus reduce morbidity and mortality in ICU.
Naloxegol is a polyethylene glycol derivative of naloxol, which is a derivative of naloxone and a peripherally acting µ-opioid receptor antagonist. Contrary to naloxone, naloxegol has a very low penetration into the central nervous system, therefore it could be a relevant option for ileus prevention without the risk of impaired sedation.
The aim of our study is to assess the efficacy of the administration of naloxegol on the onset of early constipation and early ventilator-acquired pneumonia in brain injured patients receiving opioids for analgosedation.
Detailed description
Multicenter, randomized, double-blind, placebo-controlled experimental study of Naloxegol.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Naloxegol | Experimental | Drug: NaloxegolAdministration of Naloxegol 25 mg per day by nasogastric tube (NG) or orogastric tube (OG). The administration should be started within the first 24 hours after the patient is admitted to intensive care unit and continued for the duration of the administration of the morphine derivative and until 48 hours after its discontinuation. Management of constipation and gastroparesis according to the recommendations. |
| Placebo | Placebo comparator | Drug: PlaceboAdministration of the placebo according to the same procedures as the experimental arm. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age ≥ to 18 years old
- Admission to intensive care unit for traumatic brain injury or subarachnoid hemorrhage without other life-threatening injury
- Patients under sedation with administration of opiate-agonists, μ receptor agonists (Sufentanil, Fentanyl, Remifentanil, Morphine) for less than 24 hours
- Expected duration of invasive mechanical ventilation and sedation of 48 hours or more
- Intracranial pressure monitoring
Key exclusion criteria (23 listed)
- Patient who received opioids for more than 24 hours
- Patient with refractory intracranial hypertension at the time of inclusion: intracranial hypertension requiring therapy other than analgo-sedation (thiopental, targeted temperature management, decompressive craniectomy)
- Acute or chronic renal failure with creatinine clearance <60ml / min
- Known or suspected acute gastrointestinal obstruction
- Risk of digestive perforation:
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 |
|---|---|---|
| NaloxegolAdministration of Naloxegol 25 mg per day by nasogastric tube (SNG) or orogastric tube (SOG). The administration should be started within the first 24 hours after the patient is admitted to intensive care and continued for the duration of the administration of the morphine derivative and until 48 hours after its discontinuation. | Drug | Naloxegol |
| PlaceboAdministration of the placebo according to the same procedures as the experimental arm. | Drug | Placebo |
Primary outcome
Proportion of bowel movement
Time frame: 6 days
Incidence of ventilator-acquired pneumonia
Time frame: 7 days
9 secondary outcomes
Proportion of patient-days who received the daily calorie goal (25 Kcal / kg / day)
Time frame: 10 days
Number of patients who required one or more administration of erythromycin and / or metoclopramide for vomiting occurring during enteral feeding
Time frame: 10 days
Number of patients who received one or more rectal laxative for constipation
Time frame: 10 days
Time in days of occurrence of the first bowel movement (in case of late constipation)
Time frame: 10 days
Number of patients with ventilator-acquired pneumonia after D7 of invasive mechanical ventilationventilation (after D7 of invasive mechanical ventilation)
Time frame: 10 days
Number of days without invasive mechanical ventilation
Time frame: 10 days
Duration of hospitalization in intensive care unit
Time frame: 10 days
Glasgow Outcome Scale Extended Score
Time frame: 6 month
Number of patients who experienced an episode of intracranial hypertension requiring targeted temperature management, barbiturates, or decompression craniectomy.
Time frame: 10 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2026.
- Individual participant dataSharing planned: Yes. All collected data that underlie results in a publication
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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.
Olivier Huet, PU-PH principal investigator
CHU Brest
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Naloxegol in people with Brain Injuries, run by University Hospital, Brest at 10 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 23 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: paused, as of the sponsor's last update on 16 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 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 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?
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?
Proportion of bowel movement (time frame: 6 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Jun 2026.