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

NCT01138124 | Completed Results

• 3 other identifiers: 114427EPI40634WEUSKOP4774
• Study Type: observational
• Target: 54,202
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Renal Pelvis Cancer; Restless Legs Syndrome; Epilepsy; Neuropathic Pain; Chronic Pancreatitis; Hypertension; Pancreatic Cancer; Diabetes; Renal Cancer; Renal Cell Carcinoma

Keywords

renal cell carcinoma; epidemiology; pancreatic cancer; renal cancer; renal pelvis cancer; GPRD; case-control; Gapabentin

Outcome Measures

Primary Outcomes (8)

• Number of Pancreatic Cancer Cases and Matched Controls With the Indicated Exposure to Gabapentin

  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).

  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

• Number of Pancreatic Cancer Cases and Matched Controls With the Indicated Number of Gabapentin Prescriptions

  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).

  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

• Number of Pancreatic Cancer Cases and Matched Controls With the Indicated Duration of Exposure to Gabapentin

  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).

  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

• Number of Pancreatic Cancer Cases and Matched Controls With the Indicated Cumulative Dose of Gabapentin

  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).

  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

• Number of Renal Cancer Cases and Matched Controls With the Indicated Exposure to Gabapentin

  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).

  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.

• Number of Renal Cancer Cases and Matched Controls With the Indicated Number of Gabapentin Prescriptions

  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).

  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.

• Number of Renal Cancer Cases and Matched Controls With the Indicated Duration of Exposure to Gabapentin

  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).

  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.

• Number of Renal Cancer Cases and Matched Controls With the Indicated Cumulative Dose of Gabapentin

  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).

  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.

Study Arms (1)

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

Interventions

Gabapentin prescriptions DRUG

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.

UK GPRD 1993-2008

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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.)

Sponsors & Collaborators

• GlaxoSmithKline: lead

MeSH Terms

Conditions

Restless Legs Syndrome; Epilepsy; Neuralgia; Pancreatitis, Chronic; Hypertension; Pancreatic Neoplasms; Diabetes Mellitus; Kidney Neoplasms; Carcinoma, Renal Cell

Condition Hierarchy (Ancestors)

Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Parasomnias; Mental Disorders; Brain Diseases; Central Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pancreatitis; Pancreatic Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Vascular Diseases; Cardiovascular Diseases; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Endocrine System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2010
• First Posted: June 7, 2010
• Study Start: March 1, 2010
• Primary Completion: August 1, 2010
• Study Completion: August 1, 2010
• Last Updated: May 30, 2017
• Results First Posted: January 7, 2011

Record last verified: 2017-05