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

Primary Purpose

Constipation, Analgesia

Status
Terminated
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Naloxone and Docusate
Sponsored by
CAMC Health System
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Constipation focused on measuring Enteral nutrition, Constipation, Gastrointestinal motility, Naloxone, Docusate, Bowel stimulant, Stool softener

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Charleston Area Medical Center, General Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Control

Arm Description

Sennosides liquid 5mL (8.8mg) every 6 hours plus docusate sodium liquid 10mL (100mg) every 12 hours

Outcomes

Primary Outcome Measures

Number of hours until first bowel movement

Secondary Outcome Measures

Residual volume/toleration of feeds
Average number of bowel movements per day
Escalation of opioid dose due to impaired analgesia

Full Information

First Posted
November 24, 2008
Last Updated
July 27, 2015
Sponsor
CAMC Health System
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1. Study Identification

Unique Protocol Identification Number
NCT00799201
Brief Title
Enteral Naloxone Versus a Traditional Bowel Regimen for the Prevention of Opioid Induced Constipation in Trauma Patients
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2015
Overall Recruitment Status
Terminated
Why Stopped
Naloxone became unavailable due to manufacturing shortatges requiring the study to be terminated.
Study Start Date
August 2007 (undefined)
Primary Completion Date
October 2012 (Actual)
Study Completion Date
October 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
CAMC Health System

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Constipation, Analgesia
Keywords
Enteral nutrition, Constipation, Gastrointestinal motility, Naloxone, Docusate, Bowel stimulant, Stool softener

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
3 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Control
Arm Type
Experimental
Arm Description
Sennosides liquid 5mL (8.8mg) every 6 hours plus docusate sodium liquid 10mL (100mg) every 12 hours
Intervention Type
Drug
Intervention Name(s)
Naloxone and Docusate
Other Intervention Name(s)
Narcan, Colace
Intervention Description
Naloxone 6mg (15 mL) every 6 hours plus docusate sodium liquid 10 mL (100mg) every 12 hours
Primary Outcome Measure Information:
Title
Number of hours until first bowel movement
Time Frame
While the patient is receiving continuous or scheduled narcotics
Secondary Outcome Measure Information:
Title
Residual volume/toleration of feeds
Time Frame
While the patient is receiving continuous or scheduled doses of narcotics
Title
Average number of bowel movements per day
Time Frame
While the patient is receiving continuous or scheduled narcotics
Title
Escalation of opioid dose due to impaired analgesia
Time Frame
While the patient is receiving study medications

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Audis Bethea, PharmD, BCPS
Organizational Affiliation
CAMC Health System
Official's Role
Principal Investigator
Facility Information:
Facility Name
Charleston Area Medical Center, General Hospital
City
Charleston
State/Province
West Virginia
ZIP/Postal Code
25301
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
12799407
Citation
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. doi: 10.1001/jama.289.22.2983.
Results Reference
background
PubMed Identifier
12421743
Citation
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. doi: 10.1164/rccm.2107138.
Results Reference
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PubMed Identifier
12171602
Citation
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. doi: 10.1186/1472-6939-3-3.
Results Reference
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PubMed Identifier
11902253
Citation
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. doi: 10.1097/00003246-200201000-00020. No abstract available. Erratum In: Crit Care Med 2002 Mar;30(3):726.
Results Reference
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PubMed Identifier
12845923
Citation
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. doi: 10.1093/ajhp/60.12.1264. No abstract available.
Results Reference
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PubMed Identifier
10601678
Citation
Meissner W, Schmidt U, Hartmann M, Kath R, Reinhart K. Oral naloxone reverses opioid-associated constipation. Pain. 2000 Jan;84(1):105-109. doi: 10.1016/S0304-3959(99)00185-2.
Results Reference
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PubMed Identifier
11779668
Citation
Liu M, Wittbrodt E. Low-dose oral naloxone reverses opioid-induced constipation and analgesia. J Pain Symptom Manage. 2002 Jan;23(1):48-53. doi: 10.1016/s0885-3924(01)00369-4.
Results Reference
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PubMed Identifier
14998227
Citation
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. doi: 10.1592/phco.24.2.291.33149.
Results Reference
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PubMed Identifier
16608945
Citation
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. doi: 10.1378/chest.129.4.960.
Results Reference
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PubMed Identifier
12626983
Citation
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. doi: 10.1097/01.CCM.0000053652.80849.9F.
Results Reference
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PubMed Identifier
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Citation
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Results Reference
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Enteral Naloxone Versus a Traditional Bowel Regimen for the Prevention of Opioid Induced Constipation in Trauma Patients

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