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Observational Study of Incidence Rates of Esophageal Cancer in Women Taking Medications for the Prevention or Treatment of Osteoporosis (MK-0217A-352)

This study has been completed.
Sponsor:
Collaborator:
World Health Information Science Consultants, LLC
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01077817
First received: February 26, 2010
Last updated: February 21, 2014
Last verified: February 2014
  Purpose

This is a 2-phase retrospective database study, using both case-cohort and inception (intention-to-treat) cohort analyses to evaluate any association between oral treatments for osteoporosis and the risk of esophageal cancer in women.


Condition Intervention
Esophageal Cancer
Squamous Cell Carcinoma
Adenocarcinoma
Drug: Alendronate
Drug: Etidronate
Drug: Ibandronate
Drug: Risedronate
Drug: Raloxifene

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Retrospective
Official Title: The Risk of Esophageal Cancer in Relation to the Treatment and Prevention of Osteoporosis in Women

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Percentage of Participants With Exposure to Study Drugs (Case-Cohort Analysis) [ Time Frame: Exposure to study drug at least 720 days before disease onset ] [ Designated as safety issue: No ]
    To determine the use of study drugs (alendronate, etidronate, ibandronate, risedronate, and raloxifene) among female participants with esophageal cancer (cases) and a comparison subcohort, a case-cohort analysis was performed using women meeting criteria from the General Practice Research Database (GPRD, United Kingdom). Exposure to osteoporosis drugs administered 720 days before cancer onset was determined in cases and compared to contemporaneous assessments in a comparison subcohort matched by year of birth and membership in the GPRD on the case's onset date. Cases were confirmed and case onset dates determined by electronic algorithm (based on electronic medical record data) or by medical record review.

  • Number of Cases of Esophageal Cancer Per 100,000 Woman-Years (Intent-to-Treat Analysis) [ Time Frame: Up to approximately 7.3 years of follow-up ] [ Designated as safety issue: Yes ]
    To assess the relative risk of esophageal cancer associated with osteoporosis study drugs (alendronate, etidronate, ibandronate, risedronate, and raloxifene), initiators of osteoporosis drugs and non-initiators (comparators, women sharing match criteria with the initiator) entered an inception cohort for every three-month period, beginning in the first quarter of 1996. Assignment to study drug exposure group remained fixed from the start of follow-up, analogous to an intent-to-treat analysis. The risk of esophageal cancer among initiators of study drug compared to non-initiators of study drug was estimated through calculation of a hazard ratio. For calculation of 721+ day hazard ratios, only esophageal cancer cases occurring at least 721 days from initiation of study drug were used. For calculation of 1441+ day hazard ratios, only esophageal cancer cases occurring at least 1441 days from initiation of study drug were used.


Enrollment: 684815
Study Start Date: February 2010
Study Completion Date: February 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Esophageal Cancer Cases
Participants with any United Kingdom General Practice Research Database (GPRD) Medical code for esophageal cancer (cases). Cases were confirmed and case onset dates determined by electronic algorithm (based on electronic medical record data) or by medical record review.
Drug: Alendronate
Other Name: FOSAMAX®
Drug: Etidronate
Other Name: DIDRONEL®
Drug: Ibandronate
Other Name: BONIVA®
Drug: Risedronate
Other Names:
  • ACTONEL®
  • ATELVIA®
Drug: Raloxifene
Other Name: EVISTA®
Comparison Sample (Case-Cohort)
Participants who were matched to cases by age and membership in the GPRD on the case's onset date, and had not experienced any form of esophageal cancer or Paget's Disease and had not received oral or intravenous steroids or chemotherapy or radiotherapy, as indicated by GPRD codes.
Drug: Alendronate
Other Name: FOSAMAX®
Drug: Etidronate
Other Name: DIDRONEL®
Drug: Ibandronate
Other Name: BONIVA®
Drug: Risedronate
Other Names:
  • ACTONEL®
  • ATELVIA®
Drug: Raloxifene
Other Name: EVISTA®
Non-treated Comparators
Participants who did not initiate treatment of osteoporosis with a study drug
Alendronate
Participants initiating treatment for osteoporosis with alendronate
Drug: Alendronate
Other Name: FOSAMAX®
Etidronate
Participants initiating treatment for osteoporosis with etidronate
Drug: Etidronate
Other Name: DIDRONEL®
Ibandronate
Participants initiating treatment for osteoporosis with ibandronate
Drug: Ibandronate
Other Name: BONIVA®
Risedronate
Participants initiating treatment for osteoporosis with risedronate
Drug: Risedronate
Other Names:
  • ACTONEL®
  • ATELVIA®
Raloxifene
Participants initiating treatment for osteoporosis with raloxifene
Drug: Raloxifene
Other Name: EVISTA®

  Eligibility

Ages Eligible for Study:   55 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Women who have at least two years of experience in the GPRD and are 55 or older between 1996 and 2008; all cases of esophageal cancer were identified and matched to all women in the comparison sample (all women with same year of birth drawn from the random subsample of 25,000).

Criteria

Inclusion Criteria:

  • Cases:

    • Women in the database aged 55 or older between 1996 and 2008 with diagnosis of esophageal cancer
  • Comparator Controls:

    • Each case was matched to all women in the random subcohort of 25,000 who had the same year of birth as the case and were in the database at the time of diagnosis.

Exclusion Criteria:

  • Women with diagnosis of any other cancer or Paget's Disease or who have received oral or intravenous steroids before the index date
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01077817

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
World Health Information Science Consultants, LLC
Investigators
Study Director: Alec Walker, MD, DrPH World Health Information Science Consultants, LLC
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01077817     History of Changes
Other Study ID Numbers: 0217A-352, EP02001.029, 2010_015
Study First Received: February 26, 2010
Results First Received: November 1, 2012
Last Updated: February 21, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma, Squamous Cell
Esophageal Neoplasms
Osteoporosis
Bone Diseases
Bone Diseases, Metabolic
Carcinoma
Digestive System Diseases
Digestive System Neoplasms
Esophageal Diseases
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Head and Neck Neoplasms
Musculoskeletal Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Alendronate
Etidronic Acid
Ibandronic acid
Raloxifene
Risedronic acid
Bone Density Conservation Agents
Calcium Channel Blockers
Cardiovascular Agents
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists

ClinicalTrials.gov processed this record on November 25, 2014