Effect of Naloxegol on Postoperative Ileus in Patients Undergoing Cardiac Surgery

Phase 3

Completed

• Conditions: Postoperative Ileus (Post Cardiac Surgery Constipation)
• Interventions: Drug: inert tablet; Drug: Naloxegol

• Registration Number: NCT04433390
• Lead Sponsor: CMC Ambroise Paré

Brief Summary

Postoperative ileus, defined as the transient postoperative functional inhibition of propulsive bowel activity, commonly occurs in patients after cardiac surgery and contributes to postoperative morbidity.

Naloxegol is a peripheral opioid receptor antagonist. Recent studies showed that naloxegol is effective in the treatment of chronic opioid-induced constipation but there is no data on its use in the management of postoperative ileus after cardiac surgery.

The main objective of this prospective, double-blind, randomized, placebo-controlled trial is to assess the effectiveness of the perioperative use of naloxegol in reducing the duration of the postoperative ileus in patients undergoing cardiac surgery.

Detailed Description

Digestive complications following cardiac surgery, such as paralytic ileus and Ogilvie syndrome, are frequent and worsen the prognosis of patients. They pose a real problem of care in intensive care, inducing morbidity and mortality, extended hospital stay and a significant post-operative cost.

Few treatments are effective to reduce transit recovery time, except the neostigmine which has a serious side effects including cardiac ones.

During cardiac surgery, opioid treatments are frequently used to relieve the pain like sternotomy pain.

The pharmacologic effect of opioid induces the postoperative uleus. Opioid receptors are distributed in the central nervous system, where they are involved in the perception of pain, and in the peripheral nervous system, especially in the mesenteric nervous system, where they regulate intestinal peristalsis.

Morphine receptors antagonist are a target for prevention and treatment of post operative ileus syndrome such as alvimopan and naloxone.

A therapeutic trial demonstrates a decrease in the rate of pneumonia in intensive care patient mechanically ventilated who received naloxone.

Naloxegol is a peripheral antagonist of opioid receptor, from the alvimopan family. It has been designed to antagonize the peripheral, but not central, effects of opioids at therapeutic doses. Naloxegol is a substrate for cytochrome P450 (CYP 3A4). Following oral administration, naloxegol is absorbed rapidly, with peak concentrations achieved at less than 2 hours.

After once daily administration, plasma concentration equilibrium is reached within 2-3 days with minimal accumulation.

The main route of elimination for naloxegol is hepatic. Naloxegol has been shown to be effective in randomized trials of chronic opioid induced constipation, but there is no data on its use in the postoperative ileus.

Research hypothesis: the addition of naloxegol in pre and postoperative cardiac surgery could reduce the time to transit recovery and the rate of digestive and respiratory complications.

Study Timeline

• Study First Submitted: 2020-06-12
• Study First Submitted QC: 2020-06-12
• Study First Posted: 2020-06-16
• Study Start: 2020-10-14
• Status Verified: 2021-07
• Primary Completion: 2022-01-28
• Study Completion: 2022-03-03
• Last Update Submitted: 2022-03-07
• Last Update Posted: 2022-03-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 305

Inclusion Criteria

• > 18 years old,
• Undergoing cardiac surgery with cardiopulmonary bypass,
• For women of child bearing potential without contraception, beta-HCG negative result
• Having signed a written informed consent form,
• Affiliation to the social security system.

Exclusion Criteria

• Allergy or known hypersensitivity to Naloxegol or any of the excipients or any other opioid antagonist
• Pregnant or breastfeeding women
• Severe hepatic failure, history of cirrhosis
• Moderate or severe renal failure (GFR<60ml/min)
• Concomitant treatment with a strong cytochrome P450 3A4 inhibitor
• History of acute gastro-intestinal obstruction known or suspected
• History of digestive arteritis
• Clinically relevant alteration of the blood-brain-barrier
• Cancer with increased risk of gastro-duodenal perforation
• Disorder that could alter the integrity of the gastrointestinal lining
• Regular treatment with laxative drugs
• Concomitant treatment with methadone
• Patient unable to take a drug by oral route
• Patient under protection of the adults (guardianship, curators or safeguard of justice),
• Patient included or planning to be included in another research protocol relating to medications.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo group	inert tablet	inert tablet by oral route
Naloxegol group	Naloxegol	naloxégol tablet by oral route

Primary Outcome Measures

Name	Time	Method
Evaluate the effect of perioperative naloxegol administration on the duration of postoperative ileus after cardiac surgery	5 days	Time (hour) to transit recovery after cardiac surgery

Secondary Outcome Measures

Name	Time	Method
Incidence of digestive complications	30 days	rate of digestive complications
Evaluate the effect of the administration of Naloxegol on respiratory complications	30 days	rate of respiratory complications
Evaluate the effect of the administration of Naloxegol on infectious complications	30 days	rate of infectious complications
Compare the length of hospital stay	30 days	Duration of hospital stay (days)
Compare the length of ICU stay	30 days	Duration of ICU stay (days)
Verify the effectiveness of analgesia	day 1, day2, day3	Pain Visual Analogue Scale (VAS) ranging from 0 to 10 (0=no pain, 10=worst possible pain)

Trial Locations

Locations (1)

CMC Ambroise Paré; 🇫🇷 Neuilly-sur-Seine, Neuilly Sur Seine, France