HypertensionNCT01587742
IMI PROTECT (Work Package 2): Calcium Channel Blockers and Cancer
An observational study of Hypertension, run by GlaxoSmithKline.
Trial summary
The studies described in this protocol are all performed within the framework of PROTECT (Pharmacoepidemiological Research on Outcomes of Therapeutics by a European ConsorTium) Workpackage 2 (WP2) and Workgroup 1. Read more about this study
- Who is it for?
- Ages 18 to 79 years
- Conditions the study is for
- Hypertension
- What is being tested?
- CCB use
- How many people
- 1 participants
- Where
- No sites listed yet
- Study dates
- Nov 2011to Aug 2014
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The study population will consist of CCB first-time users and non-users from January 1, 1996 to December 31, 2009, aged 18 to 79 years enrolled in the GPRD, THIN or Danish National database
Who may be able to join
- First time users or non-users of a CCB from January 1, 1996 to December 31, 2009
- Patients aged 18 to 79 years
Who cannot join
- Patients with any cancer recorded in the GPRD or the Danish database prior to cohort entry
- Patients aged less than 18 years or more than 79 years
About this study
Official title: IMI PROTECT (Work Package 2): Calcium Channel Blocker Treatments and Cancer Risk
The studies described in this protocol are all performed within the framework of PROTECT (Pharmacoepidemiological Research on Outcomes of Therapeutics by a European ConsorTium) Workpackage 2 (WP2) and Workgroup 1. The primary aim of these studies is to develop, test and disseminate methodological standards for the design, conduct and analysis of Pharmacoepidemiological (PE) studies applicable to different safety issues and using different data sources. To achieve this, results from PE studies on 5 key adverse events (AEs) performed in different databases will be evaluated. Therefore, emphasis will be on the methodological aspects of the studies in this protocol and not on the clinical consequences of the association under investigation. The standards to develop will contribute to decreasing the discrepancies in results from different studies in the future and increase the usefulness and reliability of these studies for benefit-risk assessment in the EU.
Within WP2, five possible adverse event - drug pairs have been selected for analyses; one of these includes the possible role of calcium channel blockers (CCBs) in the risk of cancer. Analyses will address the hypothesis that CCBs modify the risk of cancer (all forms of cancer combined and various groups of cancers).
Read more
This hypothesis will be investigated using two sources of data: the UK General Practice Research Database (GPRD) and the Danish national databases. Investigations in the UK may also use The Health Improvement Network (THIN).
The primary objective of the study is to investigate the possible association between use of CCBs and risk of all forms of cancer combined, among adult patients (18 to 79 years of age during the study period, January 1, 1996 to December 31, 2009). The study will be conducted using three databases with different study designs (descriptive, cohort, population based cohort study and nested case-control) across different databases (GPRD, THIN, Danish databases) and to compare the results between databases, across designs to evaluate the impact of design/database/population differences on the outcome of the studied association.
Secondary objectives are to investigate the potential association between use of CCBs and risk of all forms of breast cancer in women; all forms of prostate cancer; and all forms of colon cancer using the same age groups and databases).
Read the detailed description
Conducting studies on the possible association between CCBs and cancer using a pharmaco-epidemiological approach based on data collected in existing databases and cancer registries is challenging. The challenge lies in working within the limitations of the available data (in terms of quality and completeness) and simultaneously maximizing the value of the available data through thoughtful study design and statistical analysis.
CCBs represent a chemically and pharmacologically diverse group of agents that are widely used for the treatment of hypertension and angina. It has been proposed that CCBs may interfere with apoptosis, leading to an increased potential for abnormal cell proliferation and tumor growth. The underlying biological mechanism for this effect is thought to be linked to the role of transmembrane Ca2+. This hypothesis has been critically reviewed and results have shown that the action of CCBs on apoptosis are complex with both increases and decreases in intracellular Ca2+ linked to this form of programmed cell death (2). CCBs have also been shown to inhibit apoptosis in certain non-transformed cell lines but promote apoptosis in other non-transformed and transformed cell lines. The results from non-human genotoxicity studies have shown no link between CCB use and tumor development
Epidemiologic studies have also provided inconsistent results. While only a few follow-up analyses reported an increased risk for all cancer or breast cancer, further observational studies have so far provided no evidence to support the hypothesis that long-term use of CCBs might be carcinogenic. As a whole, these studies have been limited by lack of statistical power and/or inadequate methods for defining the exposure window of antihypertensive treatment in relation to the index date (cancer outcome), making the establishment of a causal relationship between CCBs use and risk of cancer problematical. Studies often assumed a relatively short period of CCB use (usually between 2 months and 1 year) before entering the study as users. In other cases, information on the use of CCBs was only available at study entry or during follow-up. Overall, most studies were limited by follow-up periods that could be considered too brief to measure a carcinogenic effect. The vast majority of studies collected information from electronic medical or administrative databases.
The current study aims to learn from the experience, strengths and limitations of previous research to present a best-practice approach to addressing the hypothesis in question. Combined with the objectives of the PROTECT program, we hope that this study will help to provide a framework for guiding methodological choices in future research and contribute to increasing the usefulness and reliability of pharmacoepidemiological studies for benefit-risk assessment and decision making.
- Conditions
- Hypertension
- Being tested
- CCB use
- Keywords
- Calcium channel blockers, cancer
- Medical subject headings
- Hypertension, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CCB useDrug
Prescription of CCB during the study period between January 1, 1996 to December 31, 2009. The CCBs administered to the patients include isradipine and lacidipine.
| Study group | Role | What they receive |
|---|---|---|
| Patients with a diagnosis of any cancer type | All patients of the study population with a diagnosis of any cancer type based on Read codes and ICD-10 codes Receives: Drug: CCB use | |
| Patients with a diagnosis of breast cancer | All patients of the study population with a diagnosis of breast cancer based on Read codes and ICD-10 codes Receives: Drug: CCB use | |
| Patients with a diagnosis of prostate cancer | All patients of the study population with a diagnosis of prostate cancer based on Read codes and ICD-10 codes Receives: Drug: CCB use | |
| Patients with a diagnosis of colon cancer | All patients of the study population with a diagnosis of colon cancer based on Read codes and ICD-10 codes Receives: Drug: CCB use | |
| Patients without a diagnosis of any cancer type | All patients of the study population without a diagnosis of any cancer type Receives: Drug: CCB use |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in incidence of primary cancer (all forms) cases, defined by Read codes in GPRD/THIN and ICD-10 codes in the Danish data
Measured: During Jan 1, 1996 to Dec 31, 2009 , cancer outcomes will be assessed as those occurring six months - 1 year, 1-4 years and more than 5 years following initiation of CCB therapy
Secondary outcomes (3)
Change in incidence of breast cancer cases in women only defined by Read codes in GPRD/THIN and ICD-10 codes in the Danish data
Measured: During Jan 1, 1996 to Dec 31, 2009, cancer outcomes will be assessed as those occurring six months - 1 year, 1-4 years and more than 5 years following initiation of CCB therapy
Change in incidence of prostate cancer cases only, defined by Read codes in GPRD/THIN and ICD-10 codes in the Danish data
Measured: During Jan 1, 1996 to Dec 31, 2009, cancer outcomes will be assessed as those occurring six months - 1 year, 1-4 years and more than 5 years following initiation of CCB therapy
Change in incidence of colon cancer cases only, defined by Read codes in GPRD/THIN and ICD-10 codes in the Danish data
Measured: During Jan 1, 1996 to Dec 31, 2009, cancer outcomes will be assessed as those occurring six months - 1 year, 1-4 years and more than 5 years following initiation of CCB therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2012 (estimated)
- Study startNov 2011
- Primary completionFeb 2014
- Study completionAug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypertensionStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Time perspective
- Retrospective
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01587742
- Sponsor's protocol ID
- 115736
- Other IDs
- WEUKBRE5558
- Status last verified
- Dec 2014
- First submitted
- 23 Apr 2012
- Last updated
- 23 Dec 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- IMI PROTECT (Work Package 2): Calcium Channel Blocker Treatments and Cancer Risk
- ClinicalTrials.gov ID
- NCT01587742
- Acronym / sponsor ID
- 115736
- Conditions
- Hypertension
- Keywords
- Calcium channel blockers, cancer
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- Nov 2011
- Primary completion
- Feb 2014 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 30 Apr 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The studies described in this protocol are all performed within the framework of PROTECT (Pharmacoepidemiological Research on Outcomes of Therapeutics by a European ConsorTium) Workpackage 2 (WP2) and Workgroup 1. The primary aim of these studies is to develop, test and disseminate methodological standards for the design, conduct and analysis of Pharmacoepidemiological (PE) studies applicable to different safety issues and using different data sources. To achieve this, results from PE studies on 5 key adverse events (AEs) performed in different databases will be evaluated. Therefore, emphasis will be on the methodological aspects of the studies in this protocol and not on the clinical consequences of the association under investigation. The standards to develop will contribute to decreasing the discrepancies in results from different studies in the future and increase the usefulness and reliability of these studies for benefit-risk assessment in the EU.
Within WP2, five possible adverse event - drug pairs have been selected for analyses; one of these includes the possible role of calcium channel blockers (CCBs) in the risk of cancer. Analyses will address the hypothesis that CCBs modify the risk of cancer (all forms of cancer combined and various groups of cancers).
This hypothesis will be investigated using two sources of data: the UK General Practice Research Database (GPRD) and the Danish national databases. Investigations in the UK may also use The Health Improvement Network (THIN).
The primary objective of the study is to investigate the possible association between use of CCBs and risk of all forms of cancer combined, among adult patients (18 to 79 years of age during the study period, January 1, 1996 to December 31, 2009). The study will be conducted using three databases with different study designs (descriptive, cohort, population based cohort study and nested case-control) across different databases (GPRD, THIN, Danish databases) and to compare the results between databases, across designs to evaluate the impact of design/database/population differences on the outcome of the studied association.
Secondary objectives are to investigate the potential association between use of CCBs and risk of all forms of breast cancer in women; all forms of prostate cancer; and all forms of colon cancer using the same age groups and databases).
Detailed description
Conducting studies on the possible association between CCBs and cancer using a pharmaco-epidemiological approach based on data collected in existing databases and cancer registries is challenging. The challenge lies in working within the limitations of the available data (in terms of quality and completeness) and simultaneously maximizing the value of the available data through thoughtful study design and statistical analysis.
CCBs represent a chemically and pharmacologically diverse group of agents that are widely used for the treatment of hypertension and angina. It has been proposed that CCBs may interfere with apoptosis, leading to an increased potential for abnormal cell proliferation and tumor growth. The underlying biological mechanism for this effect is thought to be linked to the role of transmembrane Ca2+. This hypothesis has been critically reviewed and results have shown that the action of CCBs on apoptosis are complex with both increases and decreases in intracellular Ca2+ linked to this form of programmed cell death (2). CCBs have also been shown to inhibit apoptosis in certain non-transformed cell lines but promote apoptosis in other non-transformed and transformed cell lines. The results from non-human genotoxicity studies have shown no link between CCB use and tumor development
Epidemiologic studies have also provided inconsistent results. While only a few follow-up analyses reported an increased risk for all cancer or breast cancer, further observational studies have so far provided no evidence to support the hypothesis that long-term use of CCBs might be carcinogenic. As a whole, these studies have been limited by lack of statistical power and/or inadequate methods for defining the exposure window of antihypertensive treatment in relation to the index date (cancer outcome), making the establishment of a causal relationship between CCBs use and risk of cancer problematical. Studies often assumed a relatively short period of CCB use (usually between 2 months and 1 year) before entering the study as users. In other cases, information on the use of CCBs was only available at study entry or during follow-up. Overall, most studies were limited by follow-up periods that could be considered too brief to measure a carcinogenic effect. The vast majority of studies collected information from electronic medical or administrative databases.
The current study aims to learn from the experience, strengths and limitations of previous research to present a best-practice approach to addressing the hypothesis in question. Combined with the objectives of the PROTECT program, we hope that this study will help to provide a framework for guiding methodological choices in future research and contribute to increasing the usefulness and reliability of pharmacoepidemiological studies for benefit-risk assessment and decision making.
Study design
- Time perspective
- Retrospective
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Patients with a diagnosis of any cancer type | – | Drug: CCB useAll patients of the study population with a diagnosis of any cancer type based on Read codes and ICD-10 codes |
| Patients with a diagnosis of breast cancer | – | Drug: CCB useAll patients of the study population with a diagnosis of breast cancer based on Read codes and ICD-10 codes |
| Patients with a diagnosis of prostate cancer | – | Drug: CCB useAll patients of the study population with a diagnosis of prostate cancer based on Read codes and ICD-10 codes |
| Patients with a diagnosis of colon cancer | – | Drug: CCB useAll patients of the study population with a diagnosis of colon cancer based on Read codes and ICD-10 codes |
| Patients without a diagnosis of any cancer type | – | Drug: CCB useAll patients of the study population without a diagnosis of any cancer type |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The study population will consist of CCB first-time users and non-users from January 1, 1996 to December 31, 2009, aged 18 to 79 years enrolled in the GPRD, THIN or Danish National database
Key inclusion criteria (2 listed)
- First time users or non-users of a CCB from January 1, 1996 to December 31, 2009
- Patients aged 18 to 79 years
Key exclusion criteria (2 listed)
- Patients with any cancer recorded in the GPRD or the Danish database prior to cohort entry
- Patients aged less than 18 years or more than 79 years
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CCB usePrescription of CCB during the study period between January 1, 1996 to December 31, 2009. The CCBs administered to the patients include isradipine and lacidipine. | Drug | Patients with a diagnosis of any cancer type, Patients with a diagnosis of breast cancer, Patients with a diagnosis of colon cancer, Patients with a diagnosis of prostate cancer, Patients without a diagnosis of any cancer type |
Primary outcome
Change in incidence of primary cancer (all forms) cases, defined by Read codes in GPRD/THIN and ICD-10 codes in the Danish data
Time frame: During Jan 1, 1996 to Dec 31, 2009 , cancer outcomes will be assessed as those occurring six months - 1 year, 1-4 years and more than 5 years following initiation of CCB therapy
3 secondary outcomes
Change in incidence of breast cancer cases in women only defined by Read codes in GPRD/THIN and ICD-10 codes in the Danish data
Time frame: During Jan 1, 1996 to Dec 31, 2009, cancer outcomes will be assessed as those occurring six months - 1 year, 1-4 years and more than 5 years following initiation of CCB therapy
Change in incidence of prostate cancer cases only, defined by Read codes in GPRD/THIN and ICD-10 codes in the Danish data
Time frame: During Jan 1, 1996 to Dec 31, 2009, cancer outcomes will be assessed as those occurring six months - 1 year, 1-4 years and more than 5 years following initiation of CCB therapy
Change in incidence of colon cancer cases only, defined by Read codes in GPRD/THIN and ICD-10 codes in the Danish data
Time frame: During Jan 1, 1996 to Dec 31, 2009, cancer outcomes will be assessed as those occurring six months - 1 year, 1-4 years and more than 5 years following initiation of CCB therapy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Dec 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
Questions about this trial
What is this clinical trial studying?
An observational study of Hypertension, run by GlaxoSmithKline.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in incidence of primary cancer (all forms) cases, defined by Read codes in GPRD/THIN and ICD-10 codes in the Danish data (time frame: During Jan 1, 1996 to Dec 31, 2009 , cancer outcomes will be assessed as those occurring six months - 1 year, 1-4 years and more than 5 years following initiation of CCB therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Dec 2014.