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

NCT05008926 | Recruiting Phase 3

• 1 other identifier: 29BRC18.0262 (NIPA)
• Study Type: interventional
• Target: 370
• Locations: 1 country
• Sites: 11

Brief 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). 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.

Conditions

Brain Injuries

Keywords

Impaired gastrointestinal transit; Subarachnoid Hemorrhage; Traumatic brain injury

Outcome Measures

Primary Outcomes (2)

• Proportion of bowel movement

  6 days

• Incidence of ventilator-acquired pneumonia

  7 days

Secondary Outcomes (9)

• Proportion of patient-days who received the daily calorie goal (25 Kcal / kg / day)

  10 days

• Number of patients who required one or more administration of erythromycin and / or metoclopramide for vomiting occurring during enteral feeding

  10 days

• Number of patients who received one or more rectal laxative for constipation

  10 days

• Time in days of occurrence of the first bowel movement (in case of late constipation)

  10 days

• Number of patients with ventilator-acquired pneumonia after D7 of invasive mechanical ventilationventilation (after D7 of invasive mechanical ventilation)

  10 days

Study Arms (2)

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.

Drug: Naloxegol

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Naloxegol 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.

Naloxegol

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Patient who received opioids for more than 24 hours
• Acute or chronic renal failure with creatinine clearance \<60ml / min
• Known or suspected acute gastrointestinal obstruction
• 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
• 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

Sponsors & Collaborators

• University Hospital, Brest: lead

Study Sites (11)

CHU de Bordeaux - Réanimation chirurgicale

Bordeaux, France, 33000, France

NOT YET RECRUITING

CHU Bordeaux

Bordeaux, 33000, France

RECRUITING

CHU Brest

Brest, 29609, France

RECRUITING

CHU Clermont-Ferrand

Clermont-Ferrand, 63003, France

NOT YET RECRUITING

CHU de Lille

Lille, 59000, France

NOT YET RECRUITING

CHU de Montpellier

Montpellier, 34295, France

RECRUITING

CHU Nantes

Nantes, 44093, France

RECRUITING

Hôpital La Pitié Salpétrière (APHP)

Paris, 75013, France

RECRUITING

CHU de Strasbourg

Strasbourg, 67098, France

ACTIVE NOT RECRUITING

CHU Tours - Hôpital BRETONNEAU

Tours, 37000, France

ACTIVE NOT RECRUITING

CHU Tours - Hôpital TROUSSEAU

Tours, 37170, France

RECRUITING

MeSH Terms

Conditions

Brain Injuries; Subarachnoid Hemorrhage; Brain Injuries, Traumatic

Interventions

naloxegol

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Intracranial Hemorrhages; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Olivier Huet, PU-PH

  CHU Brest

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Olivier Huet, PU-PH

CONTACT

+33 2 98 34 72 88; olivier.huet@chu-brest.fr

Philippe Aries, PH

CONTACT

+33 2 98 34 72 88; philippe.aries@chu-brest.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2021
• First Posted: August 17, 2021
• Study Start: March 15, 2022
• Primary Completion: March 15, 2026
• Study Completion (Estimated): September 15, 2026
• Last Updated: November 21, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data will be available beginning five years and ending fifteen years following the final study report completion
• Access Criteria: Data access requests will be reviewed by the internal committee of Brest UH. Requestors will be required to sign and complete a data access agreement

Locations

FR (11)