InflammationPhase 2NCT00770497
Efficacy Study of Pioglitazone and Ramipril Combination Therapy in Treating Non-diabetic Hypertensive Patients.
A Phase 2 study testing Pioglitazone, Pioglitazone and ramipril and Ramipril in people with Inflammation and Hypertension, run by Takeda at 13 sites in Germany.
Trial summary
The purpose of this study is to determine the effects of pioglitazone, once daily (QD), on low grade inflammation and vascular function in hypertensive patients. Read more about this study
- Who is it for?
- Ages 30 to 75 years
- Conditions the study is for
- Inflammation, Hypertension
- What is being tested?
- Pioglitazone, Pioglitazone and ramipril and Ramipril
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 172 participants
- Where
- 13 sitesGermany
- Study dates
- Mar 2007to May 2008
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Has arterial hypertension.
- Is on stable treatment with an Angiotensin Converting Enzyme inhibitor at least for 12 weeks.
- Has a high sensitive C-Reactive Protein value greater than 1.0 mg/L and less than 10.0 mg/L.
- 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
- Manifests or has newly detected diabetes mellitus type 2 according to World Health Organization criteria.
- Has Type 1 Diabetes.
- Has acute infections.
- Chronic inflammatory diseases which cause elevated CRP-values (e.g. rheumatic diseases, pyelonephritis or osteomyelitis).
- Use of acetyl salicylic acid and/or Non-steroidal Anti-inflammatory Drugs or Cox-2-inhibitors within the last 4 weeks prior to screening visit, use of Rifampicin within the last 12 weeks prior to screening visit.
- Uncontrolled hypertension (repeated blood pressure greater than 180/100 mmHg for at least three times within two weeks); persistent hypotension (systolic less than 90 mmHg) or hemodynamic instability.
Show all 23Show fewer
- Anamnestic history of hypersensitivity to the study drugs or to drugs with similar chemical structures.
- History of severe or multiple allergies.
- Treatment with any other investigational drug within 3 months before trial entry.
- Has a progressive, fatal disease.
- History of drug or alcohol abuse within the last 5 years.
- A history of significant cardiovascular (New York Heart Association stage I - IV, hemodynamic relevant aortic or mitral valve stenosis, hypertrophic obstructive cardiomyopathy), respiratory, gastrointestinal, hepatic (alanine aminotransferase greater than 2.5 times the normal reference range), renal (creatinine greater than 2.0 mg/dL), or hematological disease, history of macular edema.
- State after kidney transplantation, hemodynamic relevant renal artery stenosis (bilateral or unilateral in case of single kidney).
- Blood donation within the last 30 days.
- Serum potassium greater than 5.5 mmol/L.
- History of hyperaldosteronism.
- Treatment with thiazolidinediones within 3 months prior to screening.
- Acute myocardial infarction, open heart surgery or cerebral events (stroke/transient ischemic attack) within 30 days prior to screening visit.
- If statin therapy applicable: Change of medication within the last 12 weeks.
- History of angioneurotic edema (hereditary or idiopathic as consequence of previous Angiotensin Converting Enzyme inhibitor treatment).
- Dialysis or hemofiltration.
- Low Density Lipoprotein apheresis with dextran sulphate.
- Allergic to toxic agents derived from insects.
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
Germany13 sites
Study site
Berlin, State of Berlin
Study site
Blankenhain, Thuringia
Study site
Cologne, North Rhine-Westphalia
Study site
Deggingen, Baden-Wurttemberg
Study site
Dresden, Saxony
Study site
Essen, North Rhine-Westphalia
Study site
Hanover, Lower Saxony
Study site
Mainz, Rhineland-Palatinate
Study site
Rottweil, Baden-Wurttemberg
Study site
Schauenburg, Rhineland-Palatinate
Study site
Spaichingen, Baden-Wurttemberg
Study site
Weilersbach, Bavaria
Study site
Werne, North Rhine-Westphalia
About this study
Official title: Effect of Pioglitazone Compared to a Combination Therapy With Ramipril and to a Ramipril Monotherapy on Low Grade Inflammation and Vascular Function in Patients With Increased Cardiovascular Risk and an Activated Inflammation. A Randomized Double-blinded Phase II Study.
The purpose of this study is to determine the effects of pioglitazone, once daily (QD), on low grade inflammation and vascular function in hypertensive patients.
Read the detailed description
Patients with insulin resistance and an activated inflammation are prone for cardiovascular complications like myocardial infarction or stroke. Pharmacological interventions reducing vascular inflammation are thought to reduce cardiovascular risk in diabetic and in non-diabetic patients.
Intervention with ACE inhibitors like ramipril is an established and widely used treatment for patients with high blood pressure, proven to reduce cardiovascular risk. Treatment of non-diabetic patients with pioglitazone has shown to improve the cardiovascular risk profile in non-diabetic patients beyond its effect on blood glucose levels.
The purpose of this study is to evaluate effects on low grade inflammation and vascular function of pioglitazone in non-diabetic, hypertensive patients with pre treatment with angiotensin converting enzyme inhibitors (that will be replaced by the study medication at time of randomization).
- Conditions
- Inflammation, Hypertension
- Being tested
- Pioglitazone, Pioglitazone and ramipril, Ramipril
- Keywords
- drug effects, Hypertension, Vascular Resistance, Drug Therapy, physiopathology, vascular
- Medical subject headings
- Inflammation, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PioglitazoneDrug
Also called ACTOS®, AD4833
Pioglitazone 15 mg, tablets, orally, once daily and ramipril placebo-matching tablets, orally, once daily for two weeks; increased to:
Pioglitazone 30 mg, tablets, orally, once daily and ramipril placebo-matching tablets, orally, once daily for up to 10 weeks.
Pioglitazone and ramiprilDrug
Also called ACTOS®, AD4833
Pioglitazone 15 mg, tablets, orally, once daily and ramipril 2.5 mg, tablets, orally, once daily for two weeks; increased to:
Pioglitazone 30 mg, tablets, orally, once daily and ramipril 5 mg, tablets, orally, once daily for up to 10 weeks.
RamiprilDrug
Pioglitazone placebo-matching tablets, orally, once daily and ramipril 2.5 mg, tablets, orally, once daily for two weeks; increased to:
Pioglitazone placebo-matching tablets, orally, once daily and ramipril 5 mg, tablets, orally, once daily for up to 10 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Pioglitazone 15 mg to 30 mg QD | Experimental | Not described Receives: Drug: Pioglitazone |
| Pioglitazone 15 mg to 30 mg QD + Ramipril 2.5 mg to 5 mg QD | Active comparator | Not described Receives: Drug: Pioglitazone and ramipril |
| Ramipril 2.5 mg to 5 mg QD | Active comparator | Not described Receives: Drug: Ramipril |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the high-sensitivity C-reactive Protein value.
Measured: Week: 12.
Secondary outcomes (28)
Change from Baseline in Glucose tolerance as assessed by an oral glucose tolerance test.
Measured: Week: 12.
Change from Baseline in Insulin sensitivity according to the Homeostatic Model Assessment - Sensitivity score and Insulin Secretion.
Measured: Weeks: 6 and 12.
Change from Baseline in Glycosylated Hemoglobin levels.
Measured: Week: 12.
Change from Baseline in C-Peptide levels.
Measured: Weeks: 6 and 12.
Change from Baseline in Proinsulin intact levels.
Measured: Weeks: 6 and 12.
Change from Baseline in 24 hours Blood Pressure Profile.
Measured: Week: 12.
Change from Baseline in high-sensitivity C-reactive Protein levels.
Measured: Weeks: 6 and 10.
Change from Baseline in Adiponectin levels.
Measured: Weeks: 6 and 12.
Change from Baseline in Monocyte Chemoattractant Protein-1 levels.
Measured: Weeks: 6 and 12.
Change from Baseline in Matrix metalloproteinase-9 levels.
Measured: Weeks: 6 and 12.
Change from Baseline in P-selectin levels.
Measured: Weeks: 6 and 12.
Change from Baseline in Plasminogen Activator Inhibitor-1 levels.
Measured: Weeks: 6 and 12.
Change from Baseline in Relaxin levels.
Measured: Weeks: 6 and 12.
Change from Baseline in Endothelin 1-21 levels.
Measured: Weeks: 6 and 12.
Change from Baseline in Nitrotyrosine levels.
Measured: Weeks: 6 and 12.
Change from Baseline in Asymmetric Dimethylarginine levels.
Measured: Weeks: 6 and 12.
Change from Baseline in Myeloperoxidase levels.
Measured: Weeks: 6 and 12.
Change from Baseline in levels of Oxidative Stress as assessed by Per-Ox-Assay.
Measured: Weeks: 6 and 12.
Change from Baseline in Total Cholesterol levels.
Measured: Weeks: 6 and 12.
Change from Baseline in Triglycerides levels.
Measured: Weeks: 6 and 12.
Change from Baseline in High Density Lipoprotein levels.
Measured: Weeks: 6 and 12.
Change from Baseline in Low Density Lipoprotein levels.
Measured: Weeks: 6 and 12.
Change from Baseline in Oxidized Low Density Lipoprotein levels.
Measured: Weeks: 6 and 12.
Change from Baseline in Soluble Intercellular Adhesion Molecule levels.
Measured: Weeks: 6 and 12.
Change from Baseline in Soluble Vascular Cell Adhesion Molecule levels.
Measured: Weeks: 6 and 12.
Change from Baseline in Osteoprotegrin levels.
Measured: Weeks: 6 and 12.
Change from Baseline in 11-dihydroxy-thromboxan B2 levels.
Measured: Weeks: 6 and 12.
Change from Baseline in Placental Growth Factor levels.
Measured: Weeks: 6 and 12.
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 startMar 2007
- Primary completionMay 2008
- Study completionMay 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for InflammationStudies 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
- 172 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Medical Adviser Clinical Research, Study director, Takeda Pharma Gmbh, Aachen (Germany)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00770497
- Sponsor's protocol ID
- ATS K023
- Other IDs
- 2006-004028-35, D-PIO-110, U1111-1115-9194
- 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
- Effect of Pioglitazone Compared to a Combination Therapy With Ramipril and to a Ramipril Monotherapy on Low Grade Inflammation and Vascular Function in Patients With Increased Cardiovascular Risk and an Activated Inflammation. A Randomized Double-blinded Phase II Study.
- ClinicalTrials.gov ID
- NCT00770497
- Acronym / sponsor ID
- ATS K023
- Conditions
- Inflammation, Hypertension
- Keywords
- drug effects, Hypertension, Vascular Resistance, Drug Therapy, physiopathology, vascular
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 172 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- Mar 2007
- Primary completion
- May 2008 (actual)
- Study completion
- May 2008 (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 effects of pioglitazone, once daily (QD), on low grade inflammation and vascular function in hypertensive patients.
Detailed description
Patients with insulin resistance and an activated inflammation are prone for cardiovascular complications like myocardial infarction or stroke. Pharmacological interventions reducing vascular inflammation are thought to reduce cardiovascular risk in diabetic and in non-diabetic patients.
Intervention with ACE inhibitors like ramipril is an established and widely used treatment for patients with high blood pressure, proven to reduce cardiovascular risk. Treatment of non-diabetic patients with pioglitazone has shown to improve the cardiovascular risk profile in non-diabetic patients beyond its effect on blood glucose levels.
The purpose of this study is to evaluate effects on low grade inflammation and vascular function of pioglitazone in non-diabetic, hypertensive patients with pre treatment with angiotensin converting enzyme inhibitors (that will be replaced by the study medication at time of randomization).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Pioglitazone 15 mg to 30 mg QD | Experimental | Drug: Pioglitazone |
| Pioglitazone 15 mg to 30 mg QD + Ramipril 2.5 mg to 5 mg QD | Active comparator | Drug: Pioglitazone and ramipril |
| Ramipril 2.5 mg to 5 mg QD | Active comparator | Drug: Ramipril |
Who may qualify
- Ages
- 30 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Has arterial hypertension.
- Is on stable treatment with an Angiotensin Converting Enzyme inhibitor at least for 12 weeks.
- Has a high sensitive C-Reactive Protein value greater than 1.0 mg/L and less than 10.0 mg/L.
- 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 (23 listed)
- Manifests or has newly detected diabetes mellitus type 2 according to World Health Organization criteria.
- Has Type 1 Diabetes.
- Has acute infections.
- Chronic inflammatory diseases which cause elevated CRP-values (e.g. rheumatic diseases, pyelonephritis or osteomyelitis).
- Use of acetyl salicylic acid and/or Non-steroidal Anti-inflammatory Drugs or Cox-2-inhibitors within the last 4 weeks prior to screening visit, use of Rifampicin within the last 12 weeks prior to screening visit.
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 |
|---|---|---|
| PioglitazoneAlso: ACTOS®, AD4833Pioglitazone 15 mg, tablets, orally, once daily and ramipril placebo-matching tablets, orally, once daily for two weeks; increased to: Pioglitazone 30 mg, tablets, orally, once daily and ramipril placebo-matching tablets, orally, once daily for up to 10 weeks. | Drug | Pioglitazone 15 mg to 30 mg QD |
| Pioglitazone and ramiprilAlso: ACTOS®, AD4833Pioglitazone 15 mg, tablets, orally, once daily and ramipril 2.5 mg, tablets, orally, once daily for two weeks; increased to: Pioglitazone 30 mg, tablets, orally, once daily and ramipril 5 mg, tablets, orally, once daily for up to 10 weeks. | Drug | Pioglitazone 15 mg to 30 mg QD + Ramipril 2.5 mg to 5 mg QD |
| RamiprilPioglitazone placebo-matching tablets, orally, once daily and ramipril 2.5 mg, tablets, orally, once daily for two weeks; increased to: Pioglitazone placebo-matching tablets, orally, once daily and ramipril 5 mg, tablets, orally, once daily for up to 10 weeks. | Drug | Ramipril 2.5 mg to 5 mg QD |
Primary outcome
Change in the high-sensitivity C-reactive Protein value.
Time frame: Week: 12.
28 secondary outcomes
Change from Baseline in Glucose tolerance as assessed by an oral glucose tolerance test.
Time frame: Week: 12.
Change from Baseline in Insulin sensitivity according to the Homeostatic Model Assessment - Sensitivity score and Insulin Secretion.
Time frame: Weeks: 6 and 12.
Change from Baseline in Glycosylated Hemoglobin levels.
Time frame: Week: 12.
Change from Baseline in C-Peptide levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in Proinsulin intact levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in 24 hours Blood Pressure Profile.
Time frame: Week: 12.
Change from Baseline in high-sensitivity C-reactive Protein levels.
Time frame: Weeks: 6 and 10.
Change from Baseline in Adiponectin levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in Monocyte Chemoattractant Protein-1 levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in Matrix metalloproteinase-9 levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in P-selectin levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in Plasminogen Activator Inhibitor-1 levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in Relaxin levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in Endothelin 1-21 levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in Nitrotyrosine levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in Asymmetric Dimethylarginine levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in Myeloperoxidase levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in levels of Oxidative Stress as assessed by Per-Ox-Assay.
Time frame: Weeks: 6 and 12.
Change from Baseline in Total Cholesterol levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in Triglycerides levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in High Density Lipoprotein levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in Low Density Lipoprotein levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in Oxidized Low Density Lipoprotein levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in Soluble Intercellular Adhesion Molecule levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in Soluble Vascular Cell Adhesion Molecule levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in Osteoprotegrin levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in 11-dihydroxy-thromboxan B2 levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in Placental Growth Factor levels.
Time frame: Weeks: 6 and 12.
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.
Medical Adviser Clinical Research study director
Takeda Pharma Gmbh, Aachen (Germany)
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pioglitazone, Pioglitazone and ramipril and Ramipril in people with Inflammation and Hypertension, run by Takeda at 13 sites in Germany.
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 4 inclusion and 23 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.
Where is the study taking place?
The record lists 13 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
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 high-sensitivity C-reactive Protein value. (time frame: Week: 12.). 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.