Gabapentin and Risk of Pancreatic Cancer and Renal Cancer (GPRD)

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01138124
First received: June 3, 2010
Last updated: June 23, 2011
Last verified: June 2011
  Purpose

High doses of gabapentin are associated with pancreatic acinar cell tumors in rats, but there has been no post marketing pancreatic carcinogenicity signal with gabapentin as reported by spontaneous reports in the Adverse Events Reporting System or in the published literature. In a published case-control screening study of the association of gabapentin with 55 cancers, the only cancer that met the screening criteria for possibly increased cancer risk with gabapentin exposure was renal (including renal pelvis) cancer. This association was judged to be likely due to or substantially accentuated by confounding by cigarette smoking, hypertension, and lifestyle (Cancer Causes Control 2009;20:1821-1835).

The primary objective of this study is to determine whether exposure to gabapentin is associated with an increased risk of developing pancreatic cancer or renal cancer in the United Kingdom (UK) General Practice Research Database (GPRD). Almost all members of the UK population are registered with a General Practice, which centralizes the medical information not only from the general practitioners themselves but also from specialist referrals and hospital attendances. Over 487 General Practices contribute data to the GPRD.

The study cohort from which cases and controls are drawn is all subjects in the GPRD 1993-2008. Gabapentin was approved in the UK in May 1993. Entry into the study cohort begins Jan 1, 1993 for all those who are registered in GPRD before that time, and at the time of registration if later than Jan 1, 1993. Patients with a first diagnosis of the respective cancer 1995-2008 are risk set matched with up to 10 controls within the same General Practice for age at cohort entry (within two years), sex, and year of entry into the study cohort (within one year). For cases, the index date is the date of first diagnosis of the respective cancer. The index date for controls is set as the date at which the follow-up time from cohort entry is the same as the case. The index date is chosen so as to give the control equal follow-up time to that of the case for ascertainment of use of gabapentin. Cases and controls will be required to have at least 2 years of follow-up in the study cohort before their index date. Data on gabapentin prescriptions are obtained for cases and controls from study cohort entry to the index date.

Crude and adjusted odds ratios and 95% confidence intervals (CI) will be produced from conditional logistic regression models, with additional analyses evaluating for latency and dose-response. For pancreatic cancer, covariates are smoking, body mass index, diabetes, epilepsy, neuropathic pain, and chronic pancreatitis. For renal cancer, covariates are smoking, body mass index, diabetes, hypertension, diuretic use, epilepsy, and neuropathic pain.


Condition Intervention
Renal Pelvis Cancer
Restless Legs Syndrome
Epilepsy
Neuropathic Pain
Chronic Pancreatitis
Hypertension
Pancreatic Cancer
Diabetes
Renal Cancer
Renal Cell Carcinoma
Drug: Gabapentin prescriptions

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Retrospective
Official Title: Risk of Pancreatic Cancer and Renal Cancer in Patients Exposed to Gabapentin in the United Kingdom General Practice Research Database

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Pancreatic Cancer Cases and Matched Controls With the Indicated Exposure to Gabapentin [ Time Frame: The case index date (ID) was the date of incident pancreatic cancer diagnosis ascertained in the GPRD study cohort 1995-2008. The matched control ID was the date at which the follow-up time from his/her cohort entry was the same as that for the case ] [ Designated as safety issue: Yes ]
    Incident pancreatic cancer. Gabapentin Exposure Description: Without 2 year lag = Gabapentin prescription from cohort entry to index date. With 2 year lag = Gabapentin prescription from cohort entry to 2 years prior to index date (to control for prediagnostic prescribing for pain symptoms possibly related to cancer).

  • Number of Pancreatic Cancer Cases and Matched Controls With the Indicated Number of Gabapentin Prescriptions [ Time Frame: The case index date (ID) was the date of incident pancreatic cancer diagnosis ascertained in the GPRD study cohort 1995-2008. The matched control ID was the date at which the follow-up time from his/her cohort entry was the same as that for the case ] [ Designated as safety issue: Yes ]
    Incident pancreatic cancer. Gabapentin Exposure Description: Without 2 year lag = Gabapentin exposure from cohort entry to index date. With 2 year lag = Gabapentin exposure from cohort entry to 2 years prior to index date (to control for prediagnostic prescribing for pain symptoms possibly related to cancer). Tertiles without 2 year lag: Tertile 1 (1-2 prescriptions),Tertile 2 (3-8 prescriptions), and Tertile 3 (9-218 prescriptions). Tertile's with 2 year lag: Tertile 1 (1-2 prescriptions), Tertile 2 (3-10 prescriptions),Tertile 3 (11-191 prescriptions).

  • Number of Pancreatic Cancer Cases and Matched Controls With the Indicated Duration of Exposure to Gabapentin [ Time Frame: The case index date (ID) was the date of incident pancreatic cancer diagnosis ascertained in the GPRD study cohort 1995-2008. The matched control ID was the date at which the follow-up time from his/her cohort entry was the same as that for the case ] [ Designated as safety issue: Yes ]
    Incident pancreatic cancer. Gabapentin Exposure Description: Without 2 year lag = Gabapentin exposure from cohort entry to index date. With 2 year lag = Gabapentin exposure from cohort entry to 2 years prior to index date (to control for prediagnostic prescribing for pain symptoms possibly related to cancer). Tertile's without 2 year lag: Tertile 1 (0.01 - 1.55 months), Tertile 2 (1.56 - 6.44 months), and Tertile 3 (6.45 - 78.36 months). Tertile's with 2 year lag: Tertile 1 (0.01 - 1.78 months), Tertile 2 (1.79 - 7.20 months), and Tertile 3 (7.21 - 64.13 months).

  • Number of Pancreatic Cancer Cases and Matched Controls With the Indicated Cumulative Dose of Gabapentin [ Time Frame: The case index date (ID) was the date of incident pancreatic cancer diagnosis ascertained in the GPRD study cohort 1995-2008. The matched control ID was the date at which the follow-up time from his/her cohort entry was the same as that for the case ] [ Designated as safety issue: Yes ]
    Incident pancreatic cancer. Gabapentin Exposure Description: Without 2 year lag = Gabapentin exposure from cohort entry to index date. With 2 year lag = Gabapentin exposure from cohort entry to 2 years prior to index date (to control for prediagnostic prescribing for pain symptoms possibly related to cancer). Tertile's without 2 year lag: Tertile 1 (0.01 - 33.6 grams), Tertile 2 (33.7 - 185.0 grams), and Tertile 3 (185.1 - 7500.2 grams). Tertile's with 2 year lag: Tertile 1 (0.01 - 39.0 grams), Tertile 2 (39.1 - 210.0 grams), and Tertile 3 (210.1 - 5623.8 grams).

  • Number of Renal Cancer Cases and Matched Controls With the Indicated Exposure to Gabapentin [ Time Frame: The case index date (ID) was the date of incident renal cancer diagnosis ascertained in the GPRD study cohort 1995-2008. The matched control ID was the date at which the follow-up time from his/her cohort entry was the same as that for the case. ] [ Designated as safety issue: Yes ]
    Incident renal cancer. Gabapentin Exposure Description: Without 2 year lag = Gabapentin prescription from cohort entry to index date. With 2 year lag = Gabapentin prescription from cohort entry to 2 years prior to index date (to control for prediagnostic prescribing for pain symptoms possibly related to cancer).

  • Number of Renal Cancer Cases and Matched Controls With the Indicated Number of Gabapentin Prescriptions [ Time Frame: The case index date (ID) was the date of incident renal cancer diagnosis ascertained in the GPRD study cohort 1995-2008. The matched control ID was the date at which the follow-up time from his/her cohort entry was the same as that for the case. ] [ Designated as safety issue: Yes ]
    Incident renal cancer. Gabapentin Exposure Description: Without 2 year lag = Gabapentin exposure from cohort entry to index date. With 2 year lag = Gabapentin exposure from cohort entry to 2 years prior to index date (to control for prediagnostic prescribing for pain symptoms possibly related to cancer). Tertiles without 2 year lag: Tertile 1 (1-2 prescriptions),Tertile 2 (3-8 prescriptions), and Tertile 3 (9-218 prescriptions). Tertile's with 2 year lag: Tertile 1 (1-2 prescriptions), Tertile 2 (3-10 prescriptions),Tertile 3 (11-191 prescriptions).

  • Number of Renal Cancer Cases and Matched Controls With the Indicated Duration of Exposure to Gabapentin [ Time Frame: The case index date (ID) was the date of incident renal cancer diagnosis ascertained in the GPRD study cohort 1995-2008. The matched control ID was the date at which the follow-up time from his/her cohort entry was the same as that for the case. ] [ Designated as safety issue: Yes ]
    Incident renal cancer. Gabapentin Exposure Description: Without 2 year lag = Gabapentin exposure from cohort entry to index date. With 2 year lag = Gabapentin exposure from cohort entry to 2 years prior to index date (to control for prediagnostic prescribing for pain symptoms possibly related to cancer). Tertile's without 2 year lag: Tertile 1 (0.01 - 1.55 months), Tertile 2 (1.56 - 6.44 months), and Tertile 3 (6.45 - 78.36 months). Tertile's with 2 year lag: Tertile 1 (0.01 - 1.78 months), Tertile 2 (1.79 - 7.20 months), and Tertile 3 (7.21 - 64.13 months).

  • Number of Renal Cancer Cases and Matched Controls With the Indicated Cumulative Dose of Gabapentin [ Time Frame: The case index date (ID) was the date of incident renal cancer diagnosis ascertained in the GPRD study cohort 1995-2008. The matched control ID was the date at which the follow-up time from his/her cohort entry was the same as that for the case. ] [ Designated as safety issue: Yes ]
    Incident renal cancer. Gabapentin Exposure Description: Without 2 year lag = Gabapentin exposure from cohort entry to index date. With 2 year lag = Gabapentin exposure from cohort entry to 2 years prior to index date (to control for prediagnostic prescribing for pain symptoms possibly related to cancer). Tertile's without 2 year lag: Tertile 1 (0.01 - 33.6 grams), Tertile 2 (33.7 - 185.0 grams), and Tertile 3 (185.1 - 7500.2 grams). Tertile's with 2 year lag: Tertile 1 (0.01 - 39.0 grams), Tertile 2 (39.1 - 210.0 grams), and Tertile 3 (210.1 - 5623.8 grams).


Enrollment: 54202
Study Start Date: March 2010
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
UK GPRD 1993-2008
The study cohort from which cases and controls are drawn is all subjects in the United Kingdom (UK) General Practice Research Database (GPRD) 1993-2008. Each member of the UK population is registered with a General Practice, which centralizes the medical information not only from the general practitioners themselves but also from specialist referrals and hospital attendances. Over 487 General Practices contribute data to the GPRD. Entry into the study cohort begins Jan 1, 1993 for all those who are registered in GPRD before that time, and at the time of registration if later than Jan 1, 1993.
Drug: Gabapentin prescriptions
The exposure of interest is gabapentin use as defined by prescriptions recorded by the GPRD general practitioner (British National Formulary codes). Data on prescriptions for gabapentin will be extracted for each case and control from entry into the study cohort up to the index date (the exposure window). Gabapentin exposure will be parameterized as follows: (1) Ever versus never exposed; (2) Number of prescriptions; (3) Duration of exposure; and (4) Cumulative dose. These parameterizations will also be examined with a 2 year lag time from the index date, limiting the exposure window from entry into the study cohort up to 2 years prior to the index date.

Detailed Description:

Patients were not recruited for nor enrolled in this study. This study is a retrospective observational study. Data from medical records or insurance claims databases are anonymised and used to develop a patient cohort. All diagnoses and treatment are recorded in the course of routine medical practice. Actual number of patients could be less than , as it is possible for a patient to be represented in more than one of the four arms (See "Participant Flow: Overall Study" Table) because of the risk set sampling.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

The study cohort from which cases and controls are drawn is all subjects in the UK GPRD 1993-2008. Entry into the study cohort begins Jan 1, 1993 for all those who are registered in GPRD before that time, and at the time of registration if later than Jan 1, 1993. Follow-up ends Dec 31, 2008, or earlier if the respective cancer is diagnosed, or if the subject leaves the GPRD for any reason including death. There are several advantages to the GPRD dataset for this study. It is a large dataset with detailed longitudinal prescription data, and long term follow-up (mean 7 years) to allow for latency in carcinogenicity. It provides good representation of the elderly who are disproportionately affected by pancreatic and renal cancers, and routinely includes data recorded by general practitioners on potential risk factors such as smoking and body mass index.

Criteria

Inclusion Criteria:

  • The study cohort from which cases and controls are drawn is all subjects in the UK GPRD 1993-2008. Entry into the study cohort begins Jan 1, 1993 for all those who are registered in GPRD before that time, and at the time of registration if later than Jan 1, 1993. Follow-up ends Dec 31, 2008, or earlier if the respective cancer is diagnosed, or if the subject leaves the GPRD for any reason including death.

Exclusion Criteria:

  • Cases and controls will be required to have at least 2 years of follow-up in the study cohort before their index date (For cases, the index date is the date of first diagnosis of the respective cancer. The index date for controls is set as the date at which the follow-up time from cohort entry is the same as the case.)
  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: NCT01138124

Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT01138124     History of Changes
Other Study ID Numbers: 114427, EPI40634, WEUSKOP4774
Study First Received: June 3, 2010
Results First Received: December 16, 2010
Last Updated: June 23, 2011
Health Authority: United States: No Health Authority

Keywords provided by GlaxoSmithKline:
renal cell carcinoma
epidemiology
pancreatic cancer
renal cancer
renal pelvis cancer
GPRD
case-control
Gapabentin

Additional relevant MeSH terms:
Hypertension
Pancreatic Neoplasms
Carcinoma, Renal Cell
Neuralgia
Pancreatitis
Restless Legs Syndrome
Pancreatitis, Chronic
Carcinoma
Kidney Neoplasms
Vascular Diseases
Cardiovascular Diseases
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Pain
Neurologic Manifestations
Nervous System Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases

ClinicalTrials.gov processed this record on October 19, 2014