The NIPA study: A randomized double-blind control clinical trial Naloxegol administration to prevent opioids induced gastrointestinal motility disturbance in brain Injured PAtients.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Regional Et Universitaire De Brest

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Pathological Conditions, Signs and Symptoms [C23]

Trial duration

2 Jul 2024 → ongoing

Decision date (initial)

2024-07-02

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-512004-19-01

ClinicalTrials.gov

NCT05008926

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To evaluate the efficacy of naloxegol administration on the occurrence of early constipation and on the incidence of early ventilator-associated pneumonitis.

Secondary objectives 6

1. To assess the effect of naloxegol administration on tolerance of enteral nutrition
2. Evaluate the effect of naloxegol administration on time to first bowel movement (in case of late constipation, i.e. after D6)
3. Evaluate the effect of naloxegol administration on rectal laxative use
4. Evaluate the effect of naloxegol administration on the incidence of late-onset ventilator-associated pneumonia (>J7)
5. Evaluate the effect of naloxegol administration on ICU and neurological prognosis at 6 months
6. Evaluate the effect of naloxegol administration on the occurrence of intracranial hypertension

Conditions and MedDRA coding

Head trauma

Regulatory references

Plan to share IPD

No

IPD plan description

NA

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Age ≥ 18 years
2. Intensive care unit admission for head trauma or subarachnoid hemorrhage without other life-threatening injury
3. Sedation for neuro-protective purposes with administration of morphinomimetics (μ-receptor agonists) IVSE (Sufentanil, Fentanyl, Remifentanil, Morphine) for less than 24 hours
4. Duration of invasive mechanical ventilation and sedation estimated at 48 hours minimum
5. Intracranial pressure monitoring planned
6. Enteral feeding via oro/nasogastric tube planned
7. Affiliated with or benefiting from a social security scheme

Exclusion criteria 15

1. Patient having received morphine for sedation for more than 24 hours
2. Patient with refractory HTIC at the time of inclusion: HTIC requiring therapies other than analgesia (thiopental, targeted temperature control, decompression craniectomy)
3. Acute or chronic renal failure with creatinine clearance < 60ml/min
4. Known or suspected acute gastrointestinal obstruction (occlusive syndrome)
5. Risk of digestive perforation: - history or presence of peptic ulcer disease - Crohn's disease - ogilvie syndrome - acute diverticulitis - infiltrating gastrointestinal tumour - recurrent or advanced ovarian cancer - peritoneal metastasis - recent abdominal trauma with risk of digestive perforation
6. Concomitant treatment with strong or moderate CYP3A4 inhibitors (e.g. clarithromycin, ketaconazole, itraconazole, telithromycin, ritonavir, indinavir, saquinavir) or strong inducers (carbamazepine, rifampicin, St. John's wort)
7. Concomitant treatment with a vascular endothelial growth factor (VEGF) inhibitor.
8. Allergy to Naloxegol or any of its excipients
9. Recent history of myocardial infarction within the last 6 months, symptomatic congestive cardiovascular disease, QT ≥ 500 msec
10. Patient with medical decision for rapid palliative management
11. Pregnancy and/or breast-feeding
12. Cirrhosis Child Pugh C stage
13. Patient under legal protection (guardianship, curatorship or unable to express consent prior to current hospitalization) or deprived of liberty
14. Patient with other life-threatening injury (other than acute brain injury)
15. History of clinically significant alterations to the blood-brain barrier: primary brain tumors, metastases or other inflammatory pathologies in the CNS, active multiple sclerosis, advanced Alzheimer's disease.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Composite criterion defined by the occurrence of one of the following events: - Absence of bowel movements before D6 of hospitalisation - Incidence of VAP before D7 of hospitalisation

Secondary endpoints 9

1. Proportion of patient-days achieving the theoretical caloric objective of enteral nutrition (≥25 Kcal/kg/day)
2. Number of patients requiring erythromycin and/or metoclopramide at least once for vomiting during enteral feeding
3. Number of patients who received at least one rectal laxative for constipation
4. Time in days to first bowel movement (in case of delayed constipation)
5. Number of patients with late VAP (after 7 days of invasive mechanical ventilation)
6. Number of days without invasive mechanical ventilation
7. Length of stay in intensive care unit
8. GOSE score (Glasgow Outcome Scale Extended) at 6 months
9. Number of patients with an episode of HTIC requiring further sedation, targeted temperature control, introduction of barbiturates, or decompression craniectomy.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Regional Et Universitaire De Brest

Sponsor organisation

Centre Hospitalier Regional Et Universitaire De Brest

Address

2 Avenue Marechal Foch

City

Brest

Postcode

29200

Country

France

Scientific contact point

Organisation

Centre Hospitalier Regional Et Universitaire De Brest

Contact name

Project manager

Public contact point

Organisation

Centre Hospitalier Regional Et Universitaire De Brest

Contact name

Project manager

Locations

1 EU/EEA country · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications