Effect of Naloxegol on Postoperative Ileus in Patients Undergoing Cardiac Surgery (TRANSIT)

• ClinicalTrials.gov Identifier: NCT04433390
• Recruitment Status: Completed
• First Posted: June 16, 2020
• Last Update Posted: March 8, 2022
• Sponsor: CMC Ambroise Paré
• Information provided by (Responsible Party): CMC Ambroise Paré

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Postoperative Ileus (Post Cardiac Surgery Constipation)	Drug: Naloxegol; Drug: inert tablet	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 305 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: the nurse giving the treatment is not the outcomes assessor.
• Primary Purpose: Treatment
• Official Title: Time to Transit Recovery After Treatment With Naloxegol in Cardiac Surgery Intensive Care Trial
• Actual Study Start Date: October 14, 2020
• Actual Primary Completion Date: January 28, 2022
• Actual Study Completion Date: March 3, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Naloxegol group; naloxégol tablet by oral route	Drug: Naloxegol; one naloxegol 12.5 mg tablet will be administrated 2 hours before surgery. One 25 mg naloxegol tablet per day will be administrated from 24h post-surgery until bowel movement; for maximum 5 days.
Placebo Comparator: Placebo group; inert tablet by oral route	Drug: inert tablet; one inert tablet will be administrated 2 hours before surgery. One inert tablet per day will be administrated from 24h post-surgery until bowel movement; for maximum 5 days.

Outcome Measures

Primary Outcome Measures :

1. Evaluate the effect of perioperative naloxegol administration on the duration of postoperative ileus after cardiac surgery [ Time Frame: 5 days ]
   Time (hour) to transit recovery after cardiac surgery

Secondary Outcome Measures :

1. Incidence of digestive complications [ Time Frame: 30 days ]
   rate of digestive complications
2. Evaluate the effect of the administration of Naloxegol on respiratory complications [ Time Frame: 30 days ]
   rate of respiratory complications
3. Evaluate the effect of the administration of Naloxegol on infectious complications [ Time Frame: 30 days ]
   rate of infectious complications
4. Verify the effectiveness of analgesia [ Time Frame: day 1, day2, day3 ]
   Pain Visual Analogue Scale (VAS) ranging from 0 to 10 (0=no pain, 10=worst possible pain)
5. Compare the length of hospital stay [ Time Frame: 30 days ]
   Duration of hospital stay (days)
6. Compare the length of ICU stay [ Time Frame: 30 days ]
   Duration of ICU stay (days)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

France

CMC Ambroise Paré

Neuilly-sur-Seine, Neuilly Sur Seine, France, 92200

Sponsors and Collaborators

CMC Ambroise Paré

More Information

• Responsible Party: CMC Ambroise Paré
• ClinicalTrials.gov Identifier: NCT04433390
• Other Study ID Numbers: 2019-09
• First Posted: June 16, 2020
• Last Update Posted: March 8, 2022
• Last Verified: July 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by CMC Ambroise Paré:

Opioid induced constipation; cardiac surgery; transit recovery

Additional relevant MeSH terms:

Ileus; Constipation; Signs and Symptoms, Digestive; Intestinal Obstruction; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Naloxegol; Narcotic Antagonists; Physiological Effects of Drugs; Sensory System Agents; Peripheral Nervous System Agents