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

Primary Purpose

Brain Injuries

Status
Recruiting
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Naloxegol
Placebo
Sponsored by
University Hospital, Brest
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain Injuries focused on measuring Impaired gastrointestinal transit, Subarachnoid Hemorrhage, Traumatic brain injury

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 72 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.

Sites / Locations

  • CHU BordeauxRecruiting
  • CHU BrestRecruiting
  • CHU Clermont-Ferrand
  • CHU de MontpellierRecruiting
  • CHU NantesRecruiting
  • Hôpital La Pitié Salpétrière (APHP)Recruiting
  • CHU de Strasbourg
  • CHU Tours - Hôpital BRETONNEAU
  • CHU Tours - Hôpital TROUSSEAURecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Naloxegol

Placebo

Arm Description

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.

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

Outcomes

Primary Outcome Measures

Proportion of bowel movement
Incidence of ventilator-acquired pneumonia

Secondary Outcome Measures

Proportion of patient-days who received the daily calorie goal (25 Kcal / kg / day)
Number of patients who required one or more administration of erythromycin and / or metoclopramide for vomiting occurring during enteral feeding
Number of patients who received one or more rectal laxative for constipation
Time in days of occurrence of the first bowel movement (in case of late constipation)
Number of patients with ventilator-acquired pneumonia after D7 of invasive mechanical ventilationventilation (after D7 of invasive mechanical ventilation)
Number of days without invasive mechanical ventilation
Duration of hospitalization in intensive care unit
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"
Number of patients who experienced an episode of intracranial hypertension requiring targeted temperature management, barbiturates, or decompression craniectomy.

Full Information

First Posted
August 10, 2021
Last Updated
July 28, 2023
Sponsor
University Hospital, Brest
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1. Study Identification

Unique Protocol Identification Number
NCT05008926
Brief Title
The NIPA Study Naloxegol Administration to Prevent Opioids Induced Gastrointestinal Motility Disturbance in Brain Injured PAtients
Acronym
NIPA
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 15, 2022 (Actual)
Primary Completion Date
March 22, 2024 (Anticipated)
Study Completion Date
September 15, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Brest

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain Injuries
Keywords
Impaired gastrointestinal transit, Subarachnoid Hemorrhage, Traumatic brain injury

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
370 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Naloxegol
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Administration of the placebo according to the same procedures as the experimental arm.
Intervention Type
Drug
Intervention Name(s)
Naloxegol
Intervention Description
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
Intervention Name(s)
Placebo
Intervention Description
Administration of the placebo according to the same procedures as the experimental arm.
Primary Outcome Measure Information:
Title
Proportion of bowel movement
Time Frame
6 days
Title
Incidence of ventilator-acquired pneumonia
Time Frame
7 days
Secondary Outcome Measure Information:
Title
Proportion of patient-days who received the daily calorie goal (25 Kcal / kg / day)
Time Frame
10 days
Title
Number of patients who required one or more administration of erythromycin and / or metoclopramide for vomiting occurring during enteral feeding
Time Frame
10 days
Title
Number of patients who received one or more rectal laxative for constipation
Time Frame
10 days
Title
Time in days of occurrence of the first bowel movement (in case of late constipation)
Time Frame
10 days
Title
Number of patients with ventilator-acquired pneumonia after D7 of invasive mechanical ventilationventilation (after D7 of invasive mechanical ventilation)
Time Frame
10 days
Title
Number of days without invasive mechanical ventilation
Time Frame
10 days
Title
Duration of hospitalization in intensive care unit
Time Frame
10 days
Title
Glasgow Outcome Scale Extended Score
Description
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"
Time Frame
6 month
Title
Number of patients who experienced an episode of intracranial hypertension requiring targeted temperature management, barbiturates, or decompression craniectomy.
Time Frame
10 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Olivier Huet, PU-PH
Phone
+33 2 98 34 72 88
Email
olivier.huet@chu-brest.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Philippe Aries, PH
Phone
+33 2 98 34 72 88
Email
philippe.aries@chu-brest.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Olivier Huet, PU-PH
Organizational Affiliation
CHU Brest
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU Bordeaux
City
Bordeaux
ZIP/Postal Code
33000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hugues De Courson, PH
First Name & Middle Initial & Last Name & Degree
Hugues De Courson, PH
Facility Name
CHU Brest
City
Brest
ZIP/Postal Code
29609
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Philippe Aries, PH
First Name & Middle Initial & Last Name & Degree
Philippe Aries, PH
Facility Name
CHU Clermont-Ferrand
City
Clermont-Ferrand
ZIP/Postal Code
63003
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Russell Chabanne, PH
First Name & Middle Initial & Last Name & Degree
Russell Chabanne
Facility Name
CHU de Montpellier
City
Montpellier
ZIP/Postal Code
34295
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pierre-François PERRIGAULT
Email
pf-perrigault@chu-montpellier.fr
Facility Name
CHU Nantes
City
Nantes
ZIP/Postal Code
44093
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yannick Hourmant, PH
First Name & Middle Initial & Last Name & Degree
Yannick Hourmant
Facility Name
Hôpital La Pitié Salpétrière (APHP)
City
Paris
ZIP/Postal Code
75013
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vincent Degos, PU-PH
First Name & Middle Initial & Last Name & Degree
Vincent Degos, PU-PH
Facility Name
CHU de Strasbourg
City
Strasbourg
ZIP/Postal Code
67098
Country
France
Individual Site Status
Active, not recruiting
Facility Name
CHU Tours - Hôpital BRETONNEAU
City
Tours
ZIP/Postal Code
37000
Country
France
Individual Site Status
Active, not recruiting
Facility Name
CHU Tours - Hôpital TROUSSEAU
City
Tours
ZIP/Postal Code
37170
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Romain MIGUEL-MONTANES
Phone
02 47 47 20 45
Email
r.miguelmontanes@chu-tours.fr

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
All collected data that underlie results in a publication
IPD Sharing Time Frame
Data will be available beginning five years and ending fifteen years following the final study report completion
IPD Sharing 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

Learn more about this trial

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

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