Longitudinal Study of Patients With Opioid-Induced Constipation

This prospective hybrid longitudinal study was conducted in the United States (US), Canada, the United Kingdom (UK), and Germany. To obtain the most complete and comprehensive understanding of the burden of opioid-induced constipation (OIC) in these countries, this study used a combination of web-based, longitudinal patient survey, retrospective data abstraction from medical records, and a prospective physician survey.

The primary objective of this study was to estimate the rate of inadequate response to laxatives (LIR), which was defined as having sufficient laxative use (at least one laxative use ≥ four times per reference period), and inadequate response (defined as fewer than three bowel movements (BMs) OR at least one of the following symptoms on the Patient Assessment of Constipation Symptoms (PAC-SYM) measure scored as moderate, severe or very severe: BMs too hard, straining to have a BM, feeling like you didn't "finish" a BM, and feeling like you had to pass a BM but could not), in a cohort of non-cancer pain and cancer pain (separately) participants with OIC, by country and overall.

The secondary study objectives are as follows:

1. To estimate the rate of LIR for two subgroups: 1xLIR and 2xLIR. 1xLIR was defined as use of at least one laxative agent ≥ 4 times in the reference period while 2xLIR was defined as the use of at least two laxative agents, each used ≥ 4 times in the reference period;
2. To describe the baseline demographic and clinical characteristics, including prior health status, comorbidities, constipation-related GI symptoms, and concomitant medications of patients with OIC;
3. To describe drug utilization and self-management of OIC;
4. To describe the pre-index and post-index healthcare resource utilization and estimate costs associated with the diagnosis, treatment, and general management of OIC (including laxative use) and events attributed to OIC, including both direct and indirect costs;
5. To describe patient-reported impact of OIC on health-related quality of life, productivity, and pain management;
6. To describe patient-reported treatment satisfaction with laxative use; and
7. To describe physician-reported awareness of OIC and symptoms and understanding of patient-reported impact of OIC.

Study Overview

• Status: Completed
• Conditions: Patients With Opioid Induced Constipation

• Study Type: Observational
• Enrollment (Actual): 520

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • University of Calgary
  • Newfoundland and Labrador
    • Paradise, Newfoundland and Labrador, Canada
      • Paradise Medical Clinic
  • Ontario
    • Burlington, Ontario, Canada
      • Aviva Clinical Trial Group Inc.
    • Newmarket, Ontario, Canada
      • SKDS Research Inc.
    • Oshawa, Ontario, Canada
      • Taunton Health Centre
  • Quebec
    • St. Romuald, Quebec, Canada
      • Pro-Recherche
• United States
  • Alabama
    • Birmingham, Alabama, United States
      • Alliance Clinical Research
    • Mobile, Alabama, United States
      • Horizon Research Group, Inc
  • Arizona
    • Phoenix, Arizona, United States
      • Hope Research Institute
  • California
    • Artelia, California, United States
      • Advanced Rx Clinical Research
    • El Cajon, California, United States
      • TriWest Research Associates, LLC
    • Laguna Hills, California, United States
      • Akkiance Research Centers
    • Lajuna Hills, California, United States
      • Primecare Clinical Research
    • Los Gatos, California, United States
      • Samaritan Center for Medical Research
    • San Diego, California, United States
      • Precision Research Institute, LLC
  • Florida
    • Jacksonville, Florida, United States
      • Southeast Clinical Research, LLC
    • Sarasota, Florida, United States
      • Physician Care Clinical Research, LLC
    • South Miami, Florida, United States
      • Soth Miami Clinical Research
  • Illinois
    • Chicago, Illinois, United States
      • Chicago Anesthesia Pain Specialists
  • New Hampshire
    • Newington, New Hampshire, United States
      • ActivMed Practices & Research
  • New Jersey
    • Atco, New Jersey, United States
      • Atco Medical Associates, P.C.
  • New York
    • North Massapequa, New York, United States
      • DiGiovanna Institute for Medical Education And Research
  • North Carolina
    • Charlotte, North Carolina, United States
      • Gaffnew Health Services
  • Ohio
    • Beavercreek, Ohio, United States
      • Clinical Inquest Center Ltd
    • Canton, Ohio, United States
      • Ohio Clinical Research Partners, LLC
    • Dayton, Ohio, United States
      • Clinical Inquest Center, Ltd.
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
      • NPC Research
  • South Carolina
    • Charleston, South Carolina, United States
      • Pain Research of Charleston
    • Myrtle Beach, South Carolina, United States
      • Family Medicine of Sayebrook
  • Utah
    • Salt Lake City, Utah, United States
      • Highland Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The target population consists of patients who have been on daily opioid therapy for ≥ 4 weeks for the treatment of chronic non-cancer or cancer pain and who have opioid-induced constipation, as per patient history.

Description

Inclusion Criteria:

• Patient is receiving a minimum total daily dose of 30 mg of oral morphine, or equianalgesic amount[s] of 1 or more other opioid therapies, for a minimum of 4 weeks for chronic pain or cancer relate pain Presence of OIC in the past 2 weeks

  • (for cancer patients only) Patient has a current diagnosis of cancer that is not currently in remission and has cancer-related pain Internet access and is able and willing to complete a longitudinal web-based survey
  • Patient is able to understand and comply with the requirements of the study, as judged by the investigator (includes ability to read and write and to use

Exclusion Criteria:

• Patient is unable or refuses to provide informed consent;

  • Patient does not have access to a computer with internet connectivity, or is unable to use a computer to complete the web-based survey; Based on clinical judgment, patient has a history of chronic constipation (i.e. clinical diagnosis, note in the medical record, or patient history);
  • Patient has a history of (or current) colon cancer (primary or metastatic) (i.e., clinical diagnosis Patient has received an investigational medication to treat constipation or participated in any study involving investigational compound naloxegol within ≤90 days prior to the baseline visit

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of LIR among the OIC population	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Rate of inadequate response to first and second-line laxative treatment for OIC (1x LIR and 2x LIR).	6 months
Baseline demographic and clinical characteristics of patients with OIC (prior health status, comorbidities, GI symptoms, and concomitant medications).	12months retrospectively
Drug utilization and self-management of OIC at baseline and changes from baseline over the 24-week follow-up period.	6 months
Healthcare resource utilization profiles pre- and post-baseline	6 months
Cost of illness related to the diagnosis, treatment, and general management of OIC (including laxative use) and events attributed to OIC, including both direct and indirect costs.	6 months
Baseline constipation-associated GI symptoms and changes from baseline over the 24-week follow-up period (PAC-SYM and additional symptom questions).	6 months
Baseline health-related quality of life (PAC-QOL and EQ-5D) and changes from baseline over the 24-week follow-up period (PAC-QOL).	6 months
Loss of productivity (WPAI-SHP score) at baseline and changes from baseline over the 24-week follow-up period.	6 months
Persistence on opioid therapy at baseline and changes from baseline over the 24-week follow-up period	6 months
Treatment satisfaction with laxative use at baseline and changes from baseline over the 24-week follow-up period, for all patients taking laxatives.	6 months
Physician-reported awareness of OIC and symptoms, and understanding of patient reported impact of OIC at baseline.	6 months

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Mark Sostek, M.D., AstraZeneca; Study Director: Cathy Datto, M.D., M.S., AstraZeneca; Principal Investigator: Robert J LoCasale, Phd, MS, AstraZeneca

Publications and helpful links

General Publications

• Gupta A, Coyne KS, Datto C, Venuti C. The Burden of Opioid-Induced Constipation in Younger Patients with Chronic Noncancer Pain. Pain Med. 2018 Dec 1;19(12):2459-2468. doi: 10.1093/pm/pny002.
• LoCasale RJ, Datto C, Wilson H, Yeomans K, Coyne KS. The Burden of Opioid-Induced Constipation: Discordance Between Patient and Health Care Provider Reports. J Manag Care Spec Pharm. 2016 Mar;22(3):236-45. doi: 10.18553/jmcp.2016.22.3.236.

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: August 22, 2013
• First Submitted That Met QC Criteria: August 22, 2013
• First Posted (Estimate): August 27, 2013

Study Record Updates

• Last Update Posted (Estimate): July 8, 2015
• Last Update Submitted That Met QC Criteria: July 7, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: opioid induced constipation in patients without cancer and with cancer
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Signs and Symptoms, Digestive; Narcotic-Related Disorders; Constipation; Opioid-Induced Constipation
• Other Study ID Numbers: 12AST11894/A-12292