The NIPA study: A randomized double-blind control clinical trialNaloxegol administration to prevent opioids induced gastrointestinal motility disturbance in brain Injured PAtients.
- Conditions
- Head trauma, Gastrointestinal motility disorders, Meningeal hemorrhageTherapeutic area: Diseases [C] - Pathological Conditions, Signs and Symptoms [C23]
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 370
Age = 18 years, Intensive care unit admission for head trauma or subarachnoid hemorrhage without other life-threatening injury, Sedation for neuro-protective purposes with administration of morphinomimetics (µ-receptor agonists) IVSE (Sufentanil, Fentanyl, Remifentanil, Morphine) for less than 24 hours, Duration of invasive mechanical ventilation and sedation estimated at 48 hours minimum, Intracranial pressure monitoring planned, Enteral feeding via oro/nasogastric tube planned, Affiliated with or benefiting from a social security scheme
Patient having received morphine for sedation for more than 24 hours, Patient with medical decision for rapid palliative management, Pregnancy and/or breast-feeding, Cirrhosis Child Pugh C stage, Patient under legal protection (guardianship, curatorship or unable to express consent prior to current hospitalization) or deprived of liberty, Patient with other life-threatening injury (other than acute brain injury), 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., Patient with refractory HTIC at the time of inclusion: HTIC requiring therapies other than analgesia (thiopental, targeted temperature control, decompression craniectomy), Acute or chronic renal failure with creatinine clearance < 60ml/min, Known or suspected acute gastrointestinal obstruction (occlusive syndrome), 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, 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), Concomitant treatment with a vascular endothelial growth factor (VEGF) inhibitor., Allergy to Naloxegol or any of its excipients, Recent history of myocardial infarction within the last 6 months, symptomatic congestive cardiovascular disease, QT = 500 msec
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the efficacy of naloxegol administration on the occurrence of early constipation and on the incidence of early ventilator-associated pneumonitis.;Secondary Objective: To assess the effect of naloxegol administration on tolerance of enteral nutrition, Evaluate the effect of naloxegol administration on time to first bowel movement (in case of late constipation, i.e. after D6), Evaluate the effect of naloxegol administration on rectal laxative use, Evaluate the effect of naloxegol administration on the incidence of late-onset ventilator-associated pneumonia (>J7), Evaluate the effect of naloxegol administration on ICU and neurological prognosis at 6 months, Evaluate the effect of naloxegol administration on the occurrence of intracranial hypertension;Primary end point(s): Composite criterion defined by the occurrence of one of the following events: - Absence of bowel movement before D6 of hospitalization - Incidence of mechanically ventilated pneumonia before D7 of hospitalization
- Secondary Outcome Measures
Name Time Method Secondary end point(s):Proportion of patient-days achieving the theoretical caloric objective of enteral nutrition (=25 Kcal/kg/day);Secondary end point(s):Number of patients requiring erythromycin and/or metoclopramide at least once for vomiting during enteral feeding;Secondary end point(s):Number of patients who received at least one rectal laxative for constipation;Secondary end point(s):Time in days to first bowel movement (in case of delayed constipation);Secondary end point(s):Number of patients with late VAP (after 7 days of invasive mechanical ventilation);Secondary end point(s):Number of days without invasive mechanical ventilation;Secondary end point(s):Length of stay in intensive care unit;Secondary end point(s):GOSE score (Glasgow Outcome Scale Extended) at 6 months;Secondary end point(s):Number of patients with an episode of HTIC requiring further sedation, targeted temperature control, introduction of barbiturates, or decompression craniectomy.