Risk of Cancer Among Pantoprazole Users

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01322633
• Collaborator: (none)
• Enrollment: 61,864
• Duration (Months): 104

Study Details

Study Description

Brief Summary

The primary objective is to assess whether the risk of gastric cancer is increased in pantoprazole users compared to users of other proton pump inhibitors.

Condition or Disease	Intervention/Treatment	Phase
Esophagitis	Other: Does not apply; Other: Does not apply

Detailed Description

All subjects who met the inclusion criteria were included in the study.

Study Design

• Study Type: Observational
• Actual Enrollment: 61864 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Long-Term Prospective Observational Study of the Risk of Cancer Among Pantoprazole Users
• Study Start Date: Jul 1, 2004
• Actual Primary Completion Date: Mar 1, 2013
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Pantoprazole Patients who received treatment with pantoprazole tablets for at least 240 days within a 12-month period from 2000 through 2003.	Other: Does not apply; This is a non-interventional study, therefore the intervention type / name do not apply.
Other proton pump inhibitors Patients who received treatment with any other proton pump inhibitor for at least 240 days within a 12-month period from 1996 through 2003.	Other: Does not apply; This is a non-interventional study, therefore the intervention type / name do not apply.

Outcome Measures

Primary Outcome Measures

1. Incidence Rate of Gastric Cancer [1 year after index date up to diagnosis of gastric cancer, death, withdrawal from KPNC membership, date when other PPI participants switched to pantoprazole or end of the study (up to Year 7.5)]

   Incidence rate was expressed as cases per 100,000 person-years with 95 percent (%) confidence intervals. Incidence rates were estimated from 1 year after the index date and were censored at the earliest of following events: diagnosis of gastric cancer, death, withdrawal from KPNC membership or end of the study, whichever occurred first for pantoprazole group. For other PPI group, data was also censored in case participants switched to pantoprazole group. Index date: the earliest date at which participant had achieved 240 days of study drug exposure within a 12 month time period before the study start date. Person-year was estimated by calculating all of the years that participants in a study were followed. Person-year calculations were adjusted for anticipated mortality based on United States (US) life tables.

Secondary Outcome Measures

1. Incidence Rate of Composite Gastrointestinal Cancers [1 year after index date up to diagnosis of gastrointestinal cancer, death, withdrawal from KPNC membership, date when other PPI participants switched to pantoprazole or end of the study (up to Year 7.5)]

   Incidence rate was expressed as cases per 100,000 person-years with 95 percent (%) confidence intervals. Incidence rates were estimated from 1 year after the index date and were censored at the earliest of following events: diagnosis of cancer of colon, pancreas, liver or small intestine, death, withdrawal from KPNC membership or end of the study, whichever occurred first for pantoprazole group. For other PPI group, data was also censored in case participants switched to pantoprazole group. Index date: the earliest date at which participant had achieved 240 days of study drug exposure within a 12 month time period before the study start date. Person-year was estimated by calculating all of the years that participants in a study were followed. Person-year calculations were adjusted for anticipated mortality based on United States (US) life tables.

2. Incidence Rate of Overall Cancer [1 year after index date up to diagnosis of any cancer, death, withdrawal from KPNC membership, date when other PPI participants switched to pantoprazole or end of the study (up to Year 7.5)]

   Incidence rate was expressed as cases per 100,000 person-years with 95 percent (%) confidence intervals. Incidence rates were estimated from 1 year after the index date and were censored at the earliest of following events: diagnosis of any type of cancer (excluding non-melanoma skin cancers), death, withdrawal from KPNC membership or end of the study, whichever occurred first for pantoprazole group. For other PPI group, data was also censored in case participants switched to pantoprazole group. Index date: the earliest date at which participant had achieved 240 days of study drug exposure within a 12 month time period before the study start date. Person-year was estimated by calculating all of the years that participants in a study were followed. Person-year calculations were adjusted for anticipated mortality based on United States (US) life tables.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients who have used pantoprazole or other proton pump inhibitors, enrollment in the health maintenance organization for at least 6 months, age 18 years or older.

Exclusion Criteria:

• Use of any proton pump inhibitor before study entry, any cancer diagnosis recorded in the medical history, diagnosis of Zollinger-Ellison Syndrome in medical history.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01322633
• Other Study ID Numbers: 3001A1-100034; B1791018
• First Posted: Mar 24, 2011
• Last Update Posted: Feb 20, 2014
• Last Verified: Jan 1, 2014

• Keywords provided by Pfizer: Pantoprazole; proton pump inhibitor; gastric cancer; digestive system cancer; cancer
• Additional relevant MeSH terms: Esophagitis

Study Results

Participant Flow

Arm/Group Title	Pantoprazole	Other Proton Pump Inhibitors (PPI)
Arm/Group Description	Participants enrolled in Kaiser Permanente Northern California (KPNC) health maintenance organization who received treatment with pantoprazole (Protonix, pantoprazole sodium) tablets as per standard clinical practice for at least 240 days within a 12-month period during 4 years (from 2000 to 2003) before the start of study, were observed for up to 7.5 years.	Participants enrolled in KPNC health maintenance organization who received treatment with any PPI other than pantoprazole (any combination of omeprazole, lansoprazole, rabeprazole, or esomeprazole) as per standard clinical practice for at least 240 days within a 12-month period during 8 years (from 1996 to 2003) before the start of study, were observed for up to 7.5 years.
Period Title: Overall Study
STARTED	34178	27686
COMPLETED	34178	27686
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Pantoprazole	Other Proton Pump Inhibitors (PPI)	Total
Arm/Group Description	Participants enrolled in Kaiser Permanente Northern California (KPNC) health maintenance organization who received treatment with pantoprazole (Protonix, pantoprazole sodium) tablets as per standard clinical practice for at least 240 days within a 12-month period during 4 years (from 2000 to 2003) before the start of study, were observed for up to 7.5 years.	Participants enrolled in KPNC health maintenance organization who received treatment with any PPI other than pantoprazole (any combination of omeprazole, lansoprazole, rabeprazole, or esomeprazole) as per standard clinical practice for at least 240 days within a 12-month period during 8 years (from 1996 to 2003) before the start of study, were observed for up to 7.5 years.	Total of all reporting groups
Overall Participants	34178	27686	61864
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	59	60	60
Sex: Female, Male (Count of Participants)
Female	19033 55.7%	15611 56.4%	34644 56%
Male	15145 44.3%	12075 43.6%	27220 44%

Outcome Measures

1. Primary Outcome

Title	Incidence Rate of Gastric Cancer
Description	Incidence rate was expressed as cases per 100,000 person-years with 95 percent (%) confidence intervals. Incidence rates were estimated from 1 year after the index date and were censored at the earliest of following events: diagnosis of gastric cancer, death, withdrawal from KPNC membership or end of the study, whichever occurred first for pantoprazole group. For other PPI group, data was also censored in case participants switched to pantoprazole group. Index date: the earliest date at which participant had achieved 240 days of study drug exposure within a 12 month time period before the study start date. Person-year was estimated by calculating all of the years that participants in a study were followed. Person-year calculations were adjusted for anticipated mortality based on United States (US) life tables.
Time Frame	1 year after index date up to diagnosis of gastric cancer, death, withdrawal from KPNC membership, date when other PPI participants switched to pantoprazole or end of the study (up to Year 7.5)

Outcome Measure Data

Analysis Population Description

Analysis population included all participants who met the inclusion criteria.

Arm/Group Title	Pantoprazole	Other Proton Pump Inhibitors (PPI)
Arm/Group Description	Participants enrolled in Kaiser Permanente Northern California (KPNC) health maintenance organization who received treatment with pantoprazole (Protonix, pantoprazole sodium) tablets as per standard clinical practice for at least 240 days within a 12-month period during 4 years (from 2000 to 2003) before the start of study, were observed for up to 7.5 years.	Participants enrolled in KPNC health maintenance organization who received treatment with any PPI other than pantoprazole (any combination of omeprazole, lansoprazole, rabeprazole, or esomeprazole) as per standard clinical practice for at least 240 days within a 12-month period during 8 years (from 1996 to 2003) before the start of study, were observed for up to 7.5 years.
Measure Participants	34178	27686
Number (95% Confidence Interval) [incidence per 100000 person-years]	19.88	23.73

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pantoprazole, Other Proton Pump Inhibitors (PPI)
	Comments	Analysis was based on hazard ratio using Cox proportional hazard regression method adjusted for sex, age, cumulative PPI dose, total years of PPI treatment, diabetes, hepatitis C, hepatitis B and year of index date.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.68
	Confidence Interval	(2-Sided) 95%; 0.24 to 1.93
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Incidence Rate of Composite Gastrointestinal Cancers
Description	Incidence rate was expressed as cases per 100,000 person-years with 95 percent (%) confidence intervals. Incidence rates were estimated from 1 year after the index date and were censored at the earliest of following events: diagnosis of cancer of colon, pancreas, liver or small intestine, death, withdrawal from KPNC membership or end of the study, whichever occurred first for pantoprazole group. For other PPI group, data was also censored in case participants switched to pantoprazole group. Index date: the earliest date at which participant had achieved 240 days of study drug exposure within a 12 month time period before the study start date. Person-year was estimated by calculating all of the years that participants in a study were followed. Person-year calculations were adjusted for anticipated mortality based on United States (US) life tables.
Time Frame	1 year after index date up to diagnosis of gastrointestinal cancer, death, withdrawal from KPNC membership, date when other PPI participants switched to pantoprazole or end of the study (up to Year 7.5)

Outcome Measure Data

Analysis Population Description

Analysis population included all participants who met the inclusion criteria.

Arm/Group Title	Pantoprazole	Other Proton Pump Inhibitors (PPI)
Arm/Group Description	Participants enrolled in Kaiser Permanente Northern California (KPNC) health maintenance organization who received treatment with pantoprazole (Protonix, pantoprazole sodium) tablets as per standard clinical practice for at least 240 days within a 12-month period during 4 years (from 2000 to 2003) before the start of study, were observed for up to 7.5 years.	Participants enrolled in KPNC health maintenance organization who received treatment with any PPI other than pantoprazole (any combination of omeprazole, lansoprazole, rabeprazole, or esomeprazole) as per standard clinical practice for at least 240 days within a 12-month period during 8 years (from 1996 to 2003) before the start of study, were observed for up to 7.5 years.
Measure Participants	34178	27686
Number (95% Confidence Interval) [incidence per 100000 person-years]	168.41	129.25

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pantoprazole, Other Proton Pump Inhibitors (PPI)
	Comments	Analysis was based on hazard ratio using Cox proportional hazard regression method adjusted for sex, age, cumulative PPI dose, total years of PPI treatment, diabetes, hepatitis C, hepatitis B and year of index date.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 95%; 0.65 to 1.40
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Incidence Rate of Overall Cancer
Description	Incidence rate was expressed as cases per 100,000 person-years with 95 percent (%) confidence intervals. Incidence rates were estimated from 1 year after the index date and were censored at the earliest of following events: diagnosis of any type of cancer (excluding non-melanoma skin cancers), death, withdrawal from KPNC membership or end of the study, whichever occurred first for pantoprazole group. For other PPI group, data was also censored in case participants switched to pantoprazole group. Index date: the earliest date at which participant had achieved 240 days of study drug exposure within a 12 month time period before the study start date. Person-year was estimated by calculating all of the years that participants in a study were followed. Person-year calculations were adjusted for anticipated mortality based on United States (US) life tables.
Time Frame	1 year after index date up to diagnosis of any cancer, death, withdrawal from KPNC membership, date when other PPI participants switched to pantoprazole or end of the study (up to Year 7.5)

Outcome Measure Data

Analysis Population Description

Analysis population included all participants who met the inclusion criteria.

Arm/Group Title	Pantoprazole	Other Proton Pump Inhibitors (PPI)
Arm/Group Description	Participants enrolled in Kaiser Permanente Northern California (KPNC) health maintenance organization who received treatment with pantoprazole (Protonix, pantoprazole sodium) tablets as per standard clinical practice for at least 240 days within a 12-month period during 4 years (from 2000 to 2003) before the start of study, were observed for up to 7.5 years.	Participants enrolled in KPNC health maintenance organization who received treatment with any PPI other than pantoprazole (any combination of omeprazole, lansoprazole, rabeprazole, or esomeprazole) as per standard clinical practice for at least 240 days within a 12-month period during 8 years (from 1996 to 2003) before the start of study, were observed for up to 7.5 years.
Measure Participants	34178	27686
Number (95% Confidence Interval) [incidence per 100000 person-years]	1465.21	1369.88

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pantoprazole, Other Proton Pump Inhibitors (PPI)
	Comments	Analysis was based on hazard ratio using Cox proportional hazard regression method adjusted for sex, age, cumulative PPI dose, total years of PPI treatment, diabetes, hepatitis C, hepatitis B and year of index date.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.06
	Confidence Interval	(2-Sided) 95%; 0.93 to 1.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Adverse Event Reporting Description	The study used de-identified patient-level electronic health related databases (e-HRD), in which it was not possible to link a particular product and medical event for any participant. Thus, minimum criteria for reporting an adverse event were not available and adverse events were not reportable as individual AE reports.
Arm/Group Title	Pantoprazole		Other Proton Pump Inhibitors (PPI)
Arm/Group Description	Participants enrolled in Kaiser Permanente Northern California (KPNC) health maintenance organization who received treatment with pantoprazole (Protonix, pantoprazole sodium) tablets as per standard clinical practice for at least 240 days within a 12-month period during 4 years (from 2000 to 2003) before the start of study, were observed for up to 7.5 years.		Participants enrolled in KPNC health maintenance organization who received treatment with any PPI other than pantoprazole (any combination of omeprazole, lansoprazole, rabeprazole, or esomeprazole) as per standard clinical practice for at least 240 days within a 12-month period during 8 years (from 1996 to 2003) before the start of study, were observed for up to 7.5 years.
All Cause Mortality
	Pantoprazole		Other Proton Pump Inhibitors (PPI)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Pantoprazole		Other Proton Pump Inhibitors (PPI)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Pantoprazole		Other Proton Pump Inhibitors (PPI)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.