The NIPA Study Naloxegol Administration to Prevent Opioids Induced Gastrointestinal Motility Disturbance in Brain Injured PAtients

NCT ID: NCT05008926

Last Updated: 2025-11-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

370 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-03-15

Study Completion Date

2026-09-15

Brief Summary

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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

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Multicenter, randomized, double-blind, placebo-controlled experimental study of Naloxegol.

Conditions

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Brain Injuries

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Naloxegol

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.

Group Type EXPERIMENTAL

Naloxegol

Intervention Type DRUG

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.

Placebo

Administration of the placebo according to the same procedures as the experimental arm.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Administration of the placebo according to the same procedures as the experimental arm.

Interventions

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Naloxegol

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.

Intervention Type DRUG

Placebo

Administration of the placebo according to the same procedures as the experimental arm.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Age ≥ to 18 years old
2. Admission to intensive care unit for traumatic brain injury or subarachnoid hemorrhage without other life-threatening injury
3. Patients under sedation with administration of opiate-agonists, μ receptor agonists (Sufentanil, Fentanyl, Remifentanil, Morphine) for less than 24 hours
4. Expected duration of invasive mechanical ventilation and sedation of 48 hours or more
5. Intracranial pressure monitoring
6. Enteral feeding by oro / nasogastric tube
7. Affiliated or beneficiary of the French social security system

Exclusion Criteria

1. Patient who received opioids for more than 24 hours
2. Patient with refractory intracranial hypertension at the time of inclusion: intracranial hypertension requiring therapy other than analgo-sedation (thiopental, targeted temperature management, decompressive craniectomy)
3. Acute or chronic renal failure with creatinine clearance \<60ml / min
4. Known or suspected acute gastrointestinal obstruction
5. Risk of digestive perforation:

* history of peptic ulcer
* 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
6. 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)
7. Concomitant treatment with vascular endothelial growth factor (VEGF) inhibitor
8. Allergy to Naloxegol or one of its excipients
9. Recent history of myocardial infarction within the past 6 months, symptomatic congestive cardiovascular disease, QT ≥ 500 msec
10. Patient with a medical decision for rapid palliative care
11. Pregnancy and / or breastfeeding
12. Child Pugh C stage cirrhosis
13. Patient under legal protection or deprived of liberty
14. Patient with another life-threatening injury
15. 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Brest

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Olivier Huet, PU-PH

Role: PRINCIPAL_INVESTIGATOR

CHU Brest

Locations

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CHU de Bordeaux - Réanimation chirurgicale

Bordeaux, France, France

Site Status NOT_YET_RECRUITING

CHU Bordeaux

Bordeaux, , France

Site Status RECRUITING

CHU Brest

Brest, , France

Site Status RECRUITING

CHU Clermont-Ferrand

Clermont-Ferrand, , France

Site Status NOT_YET_RECRUITING

CHU de Lille

Lille, , France

Site Status NOT_YET_RECRUITING

CHU de Montpellier

Montpellier, , France

Site Status RECRUITING

CHU Nantes

Nantes, , France

Site Status RECRUITING

Hôpital La Pitié Salpétrière (APHP)

Paris, , France

Site Status RECRUITING

CHU de Strasbourg

Strasbourg, , France

Site Status ACTIVE_NOT_RECRUITING

CHU Tours - Hôpital BRETONNEAU

Tours, , France

Site Status ACTIVE_NOT_RECRUITING

CHU Tours - Hôpital TROUSSEAU

Tours, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Olivier Huet, PU-PH

Role: CONTACT

+33 2 98 34 72 88

Philippe Aries, PH

Role: CONTACT

+33 2 98 34 72 88

Facility Contacts

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Matthieu BIAS

Role: primary

05 57 82 10 19

Hugues De Courson, PH

Role: primary

Philippe Aries, PH

Role: primary

Russell Chabanne, PH

Role: primary

Christophe HUZ

Role: primary

0320445962

Pierre-François PERRIGAULT

Role: primary

Yannick Hourmant, PH

Role: primary

Vincent Degos, PU-PH

Role: primary

Romain MIGUEL-MONTANES

Role: primary

02 47 47 20 45

Other Identifiers

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29BRC18.0262 (NIPA)

Identifier Type: -

Identifier Source: org_study_id

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