Enteral Naloxone Versus a Traditional Bowel Regimen for the Prevention of Opioid Induced Constipation in Trauma Patients - Full Text View

Sponsored by:	CAMC Health System
Information provided by:	CAMC Health System
ClinicalTrials.gov Identifier:	NCT00799201

Purpose

The purpose of this study is to determine if enteral naloxone is more effective than a traditional bowel regimen in the prevention and treatment of constipation and impaired gastric motility in critically ill trauma patients.

Condition	Intervention	Phase
Constipation Analgesia	Drug: Naloxone and Docusate	Phase IV

MedlinePlus related topics: Constipation Injuries Wounds

Drug Information available for: Naloxone Naloxone hydrochloride Bismuth subsalicylate Dioctyl sulfosuccinic acid Docusate calcium Kaopectate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Open Label, Parallel Assignment, Efficacy Study
Official Title:	A Prospective, Randomized Trial of Enteral Naloxone Versus a Traditional Bowel Regimen in Prevention of Constipation and Decreased Gastric Motility in Critically Ill Trauma Patients

Further study details as provided by CAMC Health System:

Primary Outcome Measures:

Number of hours until first bowel movement [ Time Frame: While the patient is receiving continuous or scheduled narcotics ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Residual volume/toleration of feeds [ Time Frame: While the patient is receiving continuous or scheduled doses of narcotics ] [ Designated as safety issue: Yes ]
Average number of bowel movements per day [ Time Frame: While the patient is receiving continuous or scheduled narcotics ] [ Designated as safety issue: Yes ]
Escalation of opioid dose due to impaired analgesia [ Time Frame: While the patient is receiving study medications ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	176
Study Start Date:	August 2007
Estimated Study Completion Date:	December 2010
Estimated Primary Completion Date:	August 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Control: Experimental Sennosides liquid 5mL (8.8mg) every 6 hours plus docusate sodium liquid 10mL (100mg) every 12 hours	Drug: Naloxone and Docusate Naloxone 6mg (15 mL) every 6 hours plus docusate sodium liquid 10 mL (100mg) every 12 hours

Detailed Description:

Impaired gastric motility and constipation are common issues among patients in the intensive care setting. Contributing factors include trauma, multiple surgical procedures, lack of ambulation, and the use of opiate analgesics to control pain. Common treatments for altered gastric motility and constipation include administration of pro-motility agents, stool softeners and bowel stimulants.

Enteral feeding is considered the safest and most effective way to provide nutrition to critically ill patients. Nutrition can be delayed and/or held when impaired gastric motility and constipation are present. Studies suggest that delays in the administration of nutrition can lead to prolonged ventilator time and increased length of stay in the intensive care setting as well as an increase in mortality.

Naloxone, a competitive opioid antagonist, is most commonly administered systemically to counteract the central and peripheral effects of opioids. When administered enterally naloxone has also been found to increase gastric emptying. Studies in patients receiving enteral feeds with multiple risk factors for altered gastric motility and constipation suggest that administration of enteral naloxone can reduce the incidence and extent of altered gastric motility and aid in defecation while not totally reversing the systemic effects of the opiate being administered. Due to these findings, it appears that enterally administered naloxone would provide a significant advantage over traditional gastrointestinal stimulants in preventing constipation in critically ill patients receiving continuous administration of opiate analgesics. In addition, the use of an enterally administered opiate antagonist may also alleviate the need for routine administration of pro-kinetic agents in order to promote adequate gastrointestinal motility and toleration of enterally administered nutrition. As a result, the comparison of enteral naloxone plus a stool softener versus a traditional bowel regimen containing a stimulant and stool softener will aid in assessing the effectiveness of opiate reversal locally in the gastrointestinal tract in prevention of decreased gastric motility and constipation.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Males and non-pregnant females > 18 years of age and < 65 years of age
MSICU admission to the trauma service at the General Hospital
Scheduled for continuous infusion/administration of opiate analgesics for at least 24 hours
Access for enteral administration of medications and tube feeds
Initiation of tube feeds

Exclusion Criteria:

NPO
Pregnancy
< 18 years of age or > 65 years of age
Pancreatitis
Ileus
Large bowel obstruction present on plain X-ray or CT scan
Recent intestinal anastomosis (within 2 weeks)
Section of large bowel removed (within 2 weeks)
Contraindications to metaclopramide (Reglan) such as parkinson's disease, tardive dyskinesia, etc.
Traumatic brain injury with a glasgow coma score of at least 8
Use of pharmacologic paralytics or neuromuscular blockade (NMB)
Non-english speaking patients

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00799201

Contacts

Contact: Audis Bethea, PharmD,BCPS

304-388-6260

audis.bethea@camc.org

Locations

United States, West Virginia
Charleston Area Medical Center, General Hospital	Recruiting
Charleston, West Virginia, United States, 25301

Sponsors and Collaborators

CAMC Health System

Investigators

Principal Investigator:

Audis Bethea, PharmD, BCPS

CAMC Health System

More Information

Publications:

Ely EW, Truman B, Shintani A, Thomason JW, Wheeler AP, Gordon S, Francis J, Speroff T, Gautam S, Margolin R, Sessler CN, Dittus RS, Bernard GR. Monitoring sedation status over time in ICU patients: reliability and validity of the Richmond Agitation-Sedation Scale (RASS). JAMA. 2003 Jun 11;289(22):2983-91.

Sessler CN, Gosnell MS, Grap MJ, Brophy GM, O'Neal PV, Keane KA, Tesoro EP, Elswick RK. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med. 2002 Nov 15;166(10):1338-44.

Hawryluck LA, Harvey WR, Lemieux-Charles L, Singer PA. Consensus guidelines on analgesia and sedation in dying intensive care unit patients. BMC Med Ethics. 2002 Aug 12;3:E3.

Jacobi J, Fraser GL, Coursin DB, Riker RR, Fontaine D, Wittbrodt ET, Chalfin DB, Masica MF, Bjerke HS, Coplin WM, Crippen DW, Fuchs BD, Kelleher RM, Marik PE, Nasraway SA Jr, Murray MJ, Peruzzi WT, Lumb PD; Task Force of the American College of Critical Care Medicine (ACCM) of the Society of Critical Care Medicine (SCCM), American Society of Health-System Pharmacists (ASHP), American College of Chest Physicians. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med. 2002 Jan;30(1):119-41. No abstract available. Erratum in: Crit Care Med 2002 Mar;30(3):726.

Thomas MC, Erstad BL. Safety of enteral naloxone and i.v. neostigmine when used to relieve constipation. Am J Health Syst Pharm. 2003 Jun 15;60(12):1264-7. No abstract available.

Meissner W, Schmidt U, Hartmann M, Kath R, Reinhart K. Oral naloxone reverses opioid-associated constipation. Pain. 2000 Jan;84(1):105-9.

Liu M, Wittbrodt E. Low-dose oral naloxone reverses opioid-induced constipation and analgesia. J Pain Symptom Manage. 2002 Jan;23(1):48-53.

Mixides G, Liebl MG, Bloom K. Enteral administration of naloxone for treatment of opioid-associated intragastric feeding intolerance. Pharmacotherapy. 2004 Feb;24(2):291-4.

Artinian V, Krayem H, DiGiovine B. Effects of early enteral feeding on the outcome of critically ill mechanically ventilated medical patients. Chest. 2006 Apr;129(4):960-7.

Meissner W, Dohrn B, Reinhart K. Enteral naloxone reduces gastric tube reflux and frequency of pneumonia in critical care patients during opioid analgesia. Crit Care Med. 2003 Mar;31(3):776-80.

Mostafa SM, Bhandari S, Ritchie G, Gratton N, Wenstone R. Constipation and its implications in the critically ill patient. Br J Anaesth. 2003 Dec;91(6):815-9.

Responsible Party:	Charleston Area Medical Center ( Audis Bethea, PharmD, BCPS )
Study ID Numbers:	07-01-1897
Study First Received:	November 24, 2008
Last Updated:	January 15, 2009
ClinicalTrials.gov Identifier:	NCT00799201
Health Authority:	United States: Institutional Review Board

Keywords provided by CAMC Health System:

Enteral nutrition
Constipation
Gastrointestinal motility
Naloxone

Docusate
Bowel stimulant
Stool softener

Study placed in the following topic categories:

Signs and Symptoms
Signs and Symptoms, Digestive
Critical Illness
Constipation

Wounds and Injuries
Bismuth subsalicylate
Naloxone

Additional relevant MeSH terms:

Sensory System Agents
Therapeutic Uses
Physiological Effects of Drugs
Narcotic Antagonists

Peripheral Nervous System Agents
Central Nervous System Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009