Lubiprostone (Amitiza®) Vs. Standard Care in Opioid-induced Constipation After Surgery in Inpatient Rehabilitation

Lubiprostone (Amitiza®) Compared to Standard Care in the Treatment of Postoperative Opioid-induced Constipation in Inpatient Rehabilitation Patients Following Orthopedic Procedures

Patients requiring opioids for post-operative pain control following elective orthopedic procedures which has resulted in constipation symptoms, and who are in inpatient rehabilitation will be randomized to two different treatment arms: lubiprostone or senna. Baseline scores regarding constipation and a quality of life bowel questionnaire will be compared the day following 6 days of treatment intervention.

Study Overview

• Status: Completed
• Conditions: Constipation
• Intervention / Treatment: Drug: Lubiprostone; Drug: Senna

Detailed Description

The purpose of this study is to assess the efficacy of Lubiprostone (Amitiza) compared to standard care for the treatment of constipation in orthopedic patients receiving opioids for pain control during inpatient rehabilitation. Lubiprostone (Amitiza®) is a locally acting chloride channel activator that increases intestinal fluid, and thus increases intestinal motility. It has been approved for chronic constipation, but not in the setting of opioid-induced constipation. Senna is a stimulant laxative that increases propulsive peristaltic activity of the colon through local effects on the mucosa.

Subjects will be compared using from the Patient Assessment of Constipation (PAC) which has previously been found to be a valid and reliable way to measure constipation symptoms and clinical course. (Frank, Kleinman et al. 1999) as well as with other measures of bowel-related symptoms and functional outcomes.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60302
      • Rehabilitation Institute of Chicago

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Adult, 18 years old or greater.
2. The patient is able to provide informed consent.
3. Anticipated duration of hospitalization of at least 7 days.
4. Woman of childbearing potential must have a negative serum pregnancy test at enrollment. Exclusions for testing include two years or greater postmenopausal, hysterectomy or tubal ligation.

5. Use of opioid for post-op analgesia following orthopedic surgical procedures as defined as IV, IM, transdermal or PO opioid received within the prior 24 hours of hospitalization for pain control, and expectation that an opioid will be continued for pain control.

   • Medication may be administered on a PRN (as needed) basis or scheduled basis
   • One or greater doses has been received within the 24 hours prior to enrollment as determined by medication administration recorded from the acute care facility or RIC MAR.

6. At least one associated symptom of constipation at the time of admission, such as, but not limited to:

   • Lumpy or Hard stools
   • Feeling of incomplete evacuation of bowels
   • Abdominal cramping or pain
   • Straining with movement of bowels or painful bowel movement effort
   • Need for manual assistance to have a bowel movement

Exclusion Criteria:

1. Known allergy or sensitivity to the study medications
2. Females who are pregnant
3. Diarrhea on the day of admission
4. Diagnosis of Clostridium difficile infection during the current hospitalization

5. Pre-existing medical condition or surgical procedure, which is known to commonly lead to bowel dysfunction such as, but not limited to:

   • Crohn's disease
   • Ulcerative colitis
   • Multiple sclerosis
   • Cerebral palsy
   • Spinal Cord Injury
   • Colectomy
   • Malabsorption Syndrome
   • Irritable Bowel Syndrome
   • Abdominopelvic neoplasm (gastric, colon cancer)
   • Severe liver disease
   • Colonic or ileo-colonic resections

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lubiprostone and placebo Senna; Lubiprostone (Amitiza) 24 µg po BID given with meals for 6 days with two tabs placebo Senna at noon	Drug: Lubiprostone; 24 µg po BID given with meals for 6 days; Other Names: Amitiza
Active Comparator: Senna active plus Lubiprostone Placebo; Senna 2 tabs daily for 6 days at noon and placebo Lubiprostone 1 Cap BID	Drug: Senna; 2 tabs daily for 6 days; Other Names: Sennasides 8.6 mg each tab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Patient Assessment of Constipation (PAC) - Symptoms (Sym)	Patient Assessment of Constipation (PAC) - Change in this measure was assessed. The PAC has previously been found to be a valid and reliable way to measure constipation symptoms and clinical course. The PAC has two components. The symptom (SYM) component is composed of 12 items with score range 0-4 with lower scores indicating improvement. Scores within the two domains were separately averaged. The PAC-SYM questionnaire has shown good concurrent and clinical validity for opioid-induced constipation in a number of pain populations and has demonstrative responsiveness to treatment. There are three symptom domains within the PAC-SYM: Abdominal symptoms (4 items), rectal symptoms (3 items) and stool symptoms (5 items).	Baseline and Day 7, after treatment completed (6 days of treatment)
Change in Patient Assessment of Constipation - Quality of Life	The second component of the PAC is the quality of life (QOL) component.The quality of life (QOL) component consists of five items that are rated on a 0-4 scale with higher scores indicating better QOL. Scores within the domains are averaged.	Baseline and day 7

Collaborators and Investigators

• Sponsor: Shirley Ryan AbilityLab
• Collaborators: Takeda Pharmaceuticals North America, Inc.
• Investigators: Principal Investigator: Christina M Marciniak, MD, Shirley Ryan AbilityLab

Publications and helpful links

General Publications

• Marciniak CM, Toledo S, Lee J, Jesselson M, Bateman J, Grover B, Tierny J. Lubiprostone vs Senna in postoperative orthopedic surgery patients with opioid-induced constipation: a double-blind, active-comparator trial. World J Gastroenterol. 2014 Nov 21;20(43):16323-33. doi: 10.3748/wjg.v20.i43.16323.

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: April 16, 2008
• First Submitted That Met QC Criteria: April 17, 2008
• First Posted (Estimate): April 21, 2008

Study Record Updates

• Last Update Posted (Estimate): March 6, 2013
• Last Update Submitted That Met QC Criteria: February 27, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: opioid; rehabilitation; constipation; post-operative; orthopedic
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Signs and Symptoms, Digestive; Narcotic-Related Disorders; Constipation; Opioid-Induced Constipation; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Chloride Channel Agonists; Lubiprostone
• Other Study ID Numbers: STU00001168