NALOXEGOL OXALATE for Traumatic brain injury|Subarachnoid haemorrhage|Opioid-induced gastrointestinal motility disorder

Inclusion criteria

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

Exclusion criteria

• {"criterion_text":"- Patient having received morphine for sedation for more than 24 hours\n- Patient with medical decision for rapid palliative management\n- Pregnancy and/or breast-feeding\n- Cirrhosis Child Pugh C stage\n- Patient under legal protection (guardianship, curatorship or unable to express consent prior to current hospitalization) or deprived of liberty\n- Patient with other life-threatening injury (other than acute brain injury)\n- 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.\n- Patient with refractory HTIC at the time of inclusion: HTIC requiring therapies other than analgesia (thiopental, targeted temperature control, decompression craniectomy)\n- Acute or chronic renal failure with creatinine clearance < 60ml/min\n- Known or suspected acute gastrointestinal obstruction (occlusive syndrome)\n- 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\n- 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)\n- Concomitant treatment with a vascular endothelial growth factor (VEGF) inhibitor.\n- Allergy to Naloxegol or any of its excipients\n- Recent history of myocardial infarction within the last 6 months, symptomatic congestive cardiovascular disease, QT ≥ 500 msec"}

Primary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"Composite endpoint defined as occurrence of either: absence of bowel movements before day 6 of hospitalisation, or incidence of ventilator-associated pneumonia (VAP) before day 7 of hospitalisation."}

Secondary endpoints

• {"endpoint_text":"- Proportion of patient-days achieving the theoretical caloric objective of enteral nutrition (≥25 Kcal/kg/day)","definition_or_measurement_approach":"Proportion of patient-days during which enteral nutrition achieves ≥25 Kcal/kg/day."}
• {"endpoint_text":"- Number of patients requiring erythromycin and/or metoclopramide at least once for vomiting during enteral feeding","definition_or_measurement_approach":"Count of patients who received erythromycin and/or metoclopramide at least once for vomiting while receiving enteral feeding."}
• {"endpoint_text":"- Number of patients who received at least one rectal laxative for constipation","definition_or_measurement_approach":"Count of patients who received ≥1 rectal laxative for constipation."}
• {"endpoint_text":"- Time in days to first bowel movement (in case of delayed constipation)","definition_or_measurement_approach":"Number of days from inclusion to first bowel movement for cases of delayed constipation."}
• {"endpoint_text":"- Number of patients with late VAP (after 7 days of invasive mechanical ventilation)","definition_or_measurement_approach":"Count of patients developing ventilator-associated pneumonia occurring after 7 days of invasive mechanical ventilation."}
• {"endpoint_text":"- Number of days without invasive mechanical ventilation","definition_or_measurement_approach":"Total number of days patients were alive and free from invasive mechanical ventilation during the observation period."}
• {"endpoint_text":"- Length of stay in intensive care unit","definition_or_measurement_approach":"Duration in days of ICU stay."}
• {"endpoint_text":"- GOSE score (Glasgow Outcome Scale Extended) at 6 months","definition_or_measurement_approach":"GOSE assessment performed at 6 months post-inclusion."}
• {"endpoint_text":"- Number of patients with an episode of HTIC requiring further sedation, targeted temperature control, introduction of barbiturates, or decompression craniectomy.","definition_or_measurement_approach":"Count of patients experiencing intracranial hypertension episodes requiring additional specific therapies (additional sedation, targeted temperature control, barbiturates, or decompression craniectomy)."}

France

Earliest CTIS Part Ii Submission Date

17-06-2024

Latest Decision Or Authorization Date

11-09-2025

Processing Time Days

451

Number Of Sites

11

Number Of Participants

370

Primary sponsor

Full Name

Centre Hospitalier Regional Et Universitaire De Brest

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France