Cardiovascular DiseasesPhase 2NCT00770575
Efficacy Study of Pioglitazone and Atorvastatin Combination Therapy in Treating Subjects With Elevated Risk for Cardiovascular Disease
A Phase 2 study testing Pioglitazone and atorvastatin and Atorvastatin in people with Cardiovascular Diseases, run by Takeda.
Trial summary
The purpose of this study is to determine the effect of pioglitazone, once daily (QD), and atorvastatin combination therapy compared to atorvastatin monotherapy in patients at risk for cardiovascular disease. Read more about this study
- Who is it for?
- Ages 30 to 70 years
- Conditions the study is for
- Cardiovascular Diseases
- What is being tested?
- Pioglitazone and atorvastatin and Atorvastatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 148 participants
- Where
- No sites listed yet
- Study dates
- Jun 2005to Oct 2006
- Phase
- Phase 2
- 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 30 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Intima-media thickness of Common Carotid Artery greater than or equal to 0.8 mm (at least on one side).
- Increased cardiovascular risk defined as one or more of the following:
- medical history of infarction
- coronary angiography with proven cardiovascular disease
- instable Angina pectoris
- duplex-sonography of cervical or leg vessels with proven atherosclerotic vascular alterations
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- electrocardiogram with ischemia
- stroke
- transient ischemic attack
- peripheral arterial occlusion
- vessel surgery
- hypertension (RR greater than 140/90)
- antihypertensives
- high density lipoprotein less than 40 mg/dl.
- Body mass index greater than or equal to 25 kg/m2.
- Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.
Who cannot join
- History of overt type-2-diabetes according to the World Health Organization criteria.
- History of type-1-diabetes.
- History of more than one unexplained hypoglycemic episode within the last 6 months.
- Statin therapy within the last 4 weeks.
- Anamnestic history of hypersensitivity to the study drugs or to drugs with similar chemical structures.
- History of severe or multiple allergies.
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- Treatment with any other investigational drug within 3 months before trial entry.
- Progressive fatal disease.
- Myopathy.
- Drug or alcohol abuse within the last 5 years.
- Smoker defined as patient with evidence or history of tobacco or nicotine use within the last 6 months before the screening visit.
- A history of heart failure (New York Heart Association stage II - IV) or significant respiratory, gastrointestinal, hepatic (glutamate-pyruvate-transaminase time greater than 2.5 times the normal reference range), renal (creatinine greater than 2.0 mg/dl) or hematological disease.
- Blood donation within the last 30 days.
- Is required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:
- ciclosporin
- erythromycin
- clarithromycin
- itraconazole
- ketoconazole
- nefazodone
- niacin
- gemfibrozil and other fibrates
- HIV-Protease-Inhibitors
- Pre-treatment with thiazolidinediones within 3 months before trial entry.
About this study
Official title: Double Blinded Study of the Effects of Pioglitazone in Combination With Atorvastatin in Comparison to Atorvastatin Treatment Alone on Intima-Media Thickness in Patients at Risk for Vascular Complications
The purpose of this study is to determine the effect of pioglitazone, once daily (QD), and atorvastatin combination therapy compared to atorvastatin monotherapy in patients at risk for cardiovascular disease.
Read the detailed description
Carotid intima-media thickness is a well described surrogate marker for cardiovascular risk. A thickened carotid intima media layer correlates not only with the presence of cardiovascular risk factors but also the risk of future macrovascular events such as myocardial infarction and stroke. The interventional approach of cardiovascular risk factors with angiotensin converting enzyme system blockers, calcium antagonists or beta blockers can result in reduction of progression or even net regression of carotid intima-media thickness. The most potent agents, however, are statins which have consistently shown effects on carotid intima-media thickness in patients with hypercholesterolemia and/or atherosclerotic disease.
Peroxisome proliferator activator receptor-gamma activation by thiazolidinediones is a promising new approach which reduces insulin resistance and improves lipid profile. In addition to their metabolic activities, peroxisome proliferator activator receptor-gamma activators were shown to exert anti-inflammatory effects, to improve endothelial function and to inhibit atherogenesis in diabetic and in non-diabetic atherosclerosis-prone animal models. Treatment with peroxisome proliferator activator receptor-gamma agonists have shown to reduce arterial pressure and carotid intima-media thickness in diabetic and non-diabetic patients at risk for cardiovascular disease.
The aim of this study is to evaluate the effect of Pioglitazone in addition to Atorvastatin compared to Atorvastatin alone on vascular risk markers and intima-media thickness in patients with elevated risk for cardiovascular disease.
- Conditions
- Cardiovascular Diseases
- Being tested
- Pioglitazone and atorvastatin, Atorvastatin
- Keywords
- Biological Markers, Biochemical Markers, Carotid Artery, Internal, Carotid Artery, Common, Marker, Surrogate, Vascular Diseases, Diabetes Mellitus, Drug Therapy
- Medical subject headings
- Cardiovascular Diseases, Vascular Diseases, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pioglitazone and atorvastatinDrug
Also called ACTOS®, AD4833
Pioglitazone 30 mg, capsules, orally, once daily and atorvastatin 20 mg, tablets, orally, once daily for 4 weeks; increase to:
Pioglitazone 45 mg, capsules, orally, once daily and atorvastatin 40 mg, tablets, orally, once daily for up to 20 weeks.
AtorvastatinDrug
Pioglitazone placebo-matching capsules, orally, once daily and atorvastatin 20 mg, tablets, orally, once daily for 4 weeks; increased to
Pioglitazone placebo-matching capsules, orally, once daily and atorvastatin 40 mg, tablets, orally, once daily for up to 20 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Pioglitazone 30mg to 45 mg QD + Atorvastatin 20 mg to 40 mg QD | Experimental | Not described Receives: Drug: Pioglitazone and atorvastatin |
| Atorvastatin 20mg to 40 mg QD | Active comparator | Not described Receives: Drug: Atorvastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the intima-media thickness of the common carotid artery.
Measured: Week 24.
Secondary outcomes (11)
Change in the intima-media thickness of the internal carotid artery.
Measured: Week 24.
Change in the intima-media thickness of the carotid bulbus.
Measured: Week 24.
Change from Baseline in Efficacy Laboratory findings (Interleukin-6, high sensitive C reactive peptide and monocyte chemotactic protein-1)
Measured: Week: 24.
Change from Baseline in Efficacy Laboratory findings (matrix metalloproteinase-9, soluble CD40 Ligand, P-Selectin, soluble intracellular adhesion molecule 1 and soluble vascular cell adhesion molecule 1).
Measured: Week: 24.
Change from Baseline in Efficacy Laboratory findings (adiponectin, tissue plasminogen activator, Plasma glucose, Insulin and Intact proinsulin).
Measured: Week: 24.
Change from Baseline in Efficacy Laboratory findings (blood lipids (total cholesterol, high density lipoprotein, triglycerides) and low density lipoprotein-subfractions).
Measured: Week: 24.
Change from Baseline in Glycosylated Hemoglobin.
Measured: Week: 24.
Change from Baseline in Beta cell function (Homeostatic Model Assessment - beta cell response Score).
Measured: Week: 24.
Change from Baseline in Insulin sensitivity using the Homeostatic Model Assessment - Sensitivity Score).
Measured: Week: 24.
Change from Baseline in Microcirculation assessment.
Measured: Week: 24.
Change from Baseline in Pulse wave velocity.
Measured: Weeks: 12 and 24.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2008 (estimated)
- Study startJun 2005
- Primary completionOct 2006
- Study completionOct 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiovascular DiseasesStudies of the same condition, open and under way.
- More trials run by TakedaThe 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 148 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Head of Clinical Research/Licensing/New Products, Study director, Takeda Pharma Gmbh, Aachen (Germany)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00770575
- Sponsor's protocol ID
- ATS K015
- Other IDs
- 2004-004463-30, D-PIO-106, U1111-1115-9124, 2004
- Status last verified
- Jul 2010
- First submitted
- 9 Oct 2008
- Last updated
- 5 Jul 2010
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double Blinded Study of the Effects of Pioglitazone in Combination With Atorvastatin in Comparison to Atorvastatin Treatment Alone on Intima-Media Thickness in Patients at Risk for Vascular Complications
- ClinicalTrials.gov ID
- NCT00770575
- Acronym / sponsor ID
- ATS K015
- Conditions
- Cardiovascular Diseases
- Keywords
- Biological Markers, Biochemical Markers, Carotid Artery, Internal, Carotid Artery, Common, Marker, Surrogate, Vascular Diseases, Diabetes Mellitus, Drug Therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 148 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- Jun 2005
- Primary completion
- Oct 2006 (actual)
- Study completion
- Oct 2006 (actual)
- First posted
- 10 Oct 2008 (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 purpose of this study is to determine the effect of pioglitazone, once daily (QD), and atorvastatin combination therapy compared to atorvastatin monotherapy in patients at risk for cardiovascular disease.
Detailed description
Carotid intima-media thickness is a well described surrogate marker for cardiovascular risk. A thickened carotid intima media layer correlates not only with the presence of cardiovascular risk factors but also the risk of future macrovascular events such as myocardial infarction and stroke. The interventional approach of cardiovascular risk factors with angiotensin converting enzyme system blockers, calcium antagonists or beta blockers can result in reduction of progression or even net regression of carotid intima-media thickness. The most potent agents, however, are statins which have consistently shown effects on carotid intima-media thickness in patients with hypercholesterolemia and/or atherosclerotic disease.
Peroxisome proliferator activator receptor-gamma activation by thiazolidinediones is a promising new approach which reduces insulin resistance and improves lipid profile. In addition to their metabolic activities, peroxisome proliferator activator receptor-gamma activators were shown to exert anti-inflammatory effects, to improve endothelial function and to inhibit atherogenesis in diabetic and in non-diabetic atherosclerosis-prone animal models. Treatment with peroxisome proliferator activator receptor-gamma agonists have shown to reduce arterial pressure and carotid intima-media thickness in diabetic and non-diabetic patients at risk for cardiovascular disease.
The aim of this study is to evaluate the effect of Pioglitazone in addition to Atorvastatin compared to Atorvastatin alone on vascular risk markers and intima-media thickness in patients with elevated risk for cardiovascular disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pioglitazone 30mg to 45 mg QD + Atorvastatin 20 mg to 40 mg QD | Experimental | Drug: Pioglitazone and atorvastatin |
| Atorvastatin 20mg to 40 mg QD | Active comparator | Drug: Atorvastatin |
Who may qualify
- Ages
- 30 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Intima-media thickness of Common Carotid Artery greater than or equal to 0.8 mm (at least on one side).
- Increased cardiovascular risk defined as one or more of the following:
- Body mass index greater than or equal to 25 kg/m2.
- Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.
Key exclusion criteria (24 listed)
- History of overt type-2-diabetes according to the World Health Organization criteria.
- History of type-1-diabetes.
- History of more than one unexplained hypoglycemic episode within the last 6 months.
- Statin therapy within the last 4 weeks.
- Anamnestic history of hypersensitivity to the study drugs or to drugs with similar chemical structures.
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 |
|---|---|---|
| Pioglitazone and atorvastatinAlso: ACTOS®, AD4833Pioglitazone 30 mg, capsules, orally, once daily and atorvastatin 20 mg, tablets, orally, once daily for 4 weeks; increase to: Pioglitazone 45 mg, capsules, orally, once daily and atorvastatin 40 mg, tablets, orally, once daily for up to 20 weeks. | Drug | Pioglitazone 30mg to 45 mg QD + Atorvastatin 20 mg to 40 mg QD |
| AtorvastatinPioglitazone placebo-matching capsules, orally, once daily and atorvastatin 20 mg, tablets, orally, once daily for 4 weeks; increased to Pioglitazone placebo-matching capsules, orally, once daily and atorvastatin 40 mg, tablets, orally, once daily for up to 20 weeks. | Drug | Atorvastatin 20mg to 40 mg QD |
Primary outcome
Change in the intima-media thickness of the common carotid artery.
Time frame: Week 24.
11 secondary outcomes
Change in the intima-media thickness of the internal carotid artery.
Time frame: Week 24.
Change in the intima-media thickness of the carotid bulbus.
Time frame: Week 24.
Change from Baseline in Efficacy Laboratory findings (Interleukin-6, high sensitive C reactive peptide and monocyte chemotactic protein-1)
Time frame: Week: 24.
Change from Baseline in Efficacy Laboratory findings (matrix metalloproteinase-9, soluble CD40 Ligand, P-Selectin, soluble intracellular adhesion molecule 1 and soluble vascular cell adhesion molecule 1).
Time frame: Week: 24.
Change from Baseline in Efficacy Laboratory findings (adiponectin, tissue plasminogen activator, Plasma glucose, Insulin and Intact proinsulin).
Time frame: Week: 24.
Change from Baseline in Efficacy Laboratory findings (blood lipids (total cholesterol, high density lipoprotein, triglycerides) and low density lipoprotein-subfractions).
Time frame: Week: 24.
Change from Baseline in Glycosylated Hemoglobin.
Time frame: Week: 24.
Change from Baseline in Beta cell function (Homeostatic Model Assessment - beta cell response Score).
Time frame: Week: 24.
Change from Baseline in Insulin sensitivity using the Homeostatic Model Assessment - Sensitivity Score).
Time frame: Week: 24.
Change from Baseline in Microcirculation assessment.
Time frame: Week: 24.
Change from Baseline in Pulse wave velocity.
Time frame: Weeks: 12 and 24.
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 5 Jul 2010.
- ACTOS® Package InsertLink provided by the sponsor.
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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.
Head of Clinical Research/Licensing/New Products study director
Takeda Pharma Gmbh, Aachen (Germany)
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pioglitazone and atorvastatin and Atorvastatin in people with Cardiovascular Diseases, run by Takeda.
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 16 inclusion and 24 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 5 Jul 2010. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 the intima-media thickness of the common carotid artery. (time frame: Week 24.). 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 5 Jul 2010.