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Trial registered on ANZCTR


Registration number
ACTRN12608000534381
Ethics application status
Approved
Date submitted
19/09/2008
Date registered
21/10/2008
Date last updated
21/10/2008
Type of registration
Retrospectively registered

Titles & IDs
Public title
Double blind, randomised, comparative, multicentre, parallel-group study design to evaluate the effects of Pioglitazone on cardiovascular risk markers in type 2 diabetes mellitus
Scientific title
In patients with type 2 diabetes the evaluation of Pioglitazone versus glibenclamide or metformin on markers of inflammation, platelets activation, thrombogenesis and oxidative stress
Universal Trial Number (UTN)
Trial acronym
PRISCA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes 3728 0
Condition category
Condition code
Metabolic and Endocrine 3899 3899 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Pioglitazone via oral route 30-45 mg/day for a period of 16 weeks.
At randomization Pioglitazone 30 mg/day will be given. At follow-up visits response to treatment will be assessed. Patient should be considered as non responder and it is suggested to be titrated to on higher dose (45 mg/day) when fasting blood glucose is >140mg/dL.
Intervention code [1] 3441 0
Prevention
Comparator / control treatment
Control group 1 for patients with Body Mass Index (BMI) <27: Glibenclamide via oral route 5-15 mg/day for a period of 16 weeks.
At randomization Glibenclamide 5 mg/day will be given. At follow-up visits response to treatment will be assessed. Patient should be considered as non responder and it is suggested to be titrated to on higher dose (10 or 15 mg/day) when fasting blood glucose is >140mg/dL.

Control group 2 for patients with BMI>=27: Metformin via oral route 850-2550 mg/day for a period of 16 weeks.
At randomization Metformin 850 mg/day will be given. At follow-up visits response to treatment will be assessed. Patient should be considered as non responder and it is suggested to be titrated to on higher dose (1700 or 2550 mg/day) when fasting blood glucose is >140mg/dL.
Control group
Active

Outcomes
Primary outcome [1] 4867 0
Change from baseline of C-reactive protein assessed by blood analysis
Timepoint [1] 4867 0
The overall treatment period was of 16 weeks. The parameter will be evaluated at randomization and after 8 and 16 weeks after randomization.
Secondary outcome [1] 8098 0
Changes from baseline of markers of inflammatory response: adhesion proteins (P-selectin, E-selectin, Intracellular Cell Adhesion Molecule-1 [ICAM-1] and Vascular Cell Adhesion Molecule-1 [VCAM-1]), CD40L and Interleukin-6 [IL-6] assessed by blood analysis
Timepoint [1] 8098 0
The parameters will be evaluated at randomization and 8 and 16 weeks after randomization.
Secondary outcome [2] 8211 0
Changes from baseline of markers of platelet activation and thrombogenesis (urinary levels of 11-dehydroThromboxane B2, circulating levels of Tissue Factor [TF], Plasminogen Activator Inhibitor-1 [PAI-1]) assessed by urinary and blood analysis
Timepoint [2] 8211 0
The parameters will be evaluated at randomization and 8 and 16 weeks after randomization.
Secondary outcome [3] 8212 0
Changes from baseline of markers of oxidative stress (8-iso-prostaglandin-F2 alpha, nitro-tirosine) assessed by urinary and blood analysis
Timepoint [3] 8212 0
The parameters will be evaluated at randomization and 8 and 16 weeks after randomization.
Secondary outcome [4] 8213 0
Changes from baseline of standard glucidic parameters (fasting blood glucose, Glycosilated haemoglobin [HbA1c], serum insulin)assessed by blood analysis
Timepoint [4] 8213 0
Fasting blood glucose will be evaluated at randomization and 4, 8 and 16 weeks after randomization.
HbA1c will be evaluated at the start of a run-in period (one week before randomization), and 8 and 16 weeks after randomization.
Insulin will be evaluated at randomization and 8 and 16 weeks after randomization.
Secondary outcome [5] 8214 0
Changes from baseline of standard lipidic parameters (total cholesterol, High Density Lipoprotein Cholesterol [HDL-C], Low Density Lipoprotein Cholesterol [LDL-C], Very Low Density Lipoprotein Cholesterol [VLDL-C], triglycerides, free fatty acids) assessed by blood analysis
Timepoint [5] 8214 0
The parameters will be evaluated at randomization and 16 weeks after randomization.
Secondary outcome [6] 8215 0
Safety of the investigational study drug by adverse event recording will be assessed and standard haematology and blood chemistry parameters and vital signs will be measured.
For example the decrease in the levels of liver enzymes will be evaluated by haematology parameters.
Timepoint [6] 8215 0
Adverse events will be recorded at 4,8 and 16 weeks after randomization.

Eligibility
Key inclusion criteria
diagnosis of type 2 diabetes mellitus
age >=35 and <=75 years
subjects of either sex
HbA1c levels <=9.0%
treatment only by diet from at least 3 months
female patients had to be postmenopausal, hysterectomised or surgically sterilized or using reliable and adequate contraceptive methods (oral contraception or Intra-uterine Devices [IUD])
female (childbearing potential) patients had to show a negative response to pregnancy test
a co-operative attitude and ability to be trained to use correctly the investigational study drugs and to attain the study procedures
written informed consent provided
Minimum age
35 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Type 1 diabetes mellitus;
Treatment with other oral antidiabetics drugs or insulin in the 3 months preceding study entry;
Pregnant or lactating females;
Any disease with malabsorption;
Acute or chronic pancreatitis;
Familiar polyposis coli;
Past medical history of myocardial infarction, transient ischemic attacks (TIAs) or stroke;
Congestive heart failure (New York Heart Association [NYHA] I-IV class);
Significant liver (Alanine aminoytransferase [ALT] > 2.5 upper limit of normal range) or renal (serum creatinine > 1.2 mg/dL) impairment;
Anaemia of any aetiology (defined as haemoglobin levels < 10.5 g/dL) or any other clinically relevant haematological disease;
Diagnosis or suspicion of any neoplastic disease;
History of chronic alcohol or drug/substance abuse, or presence of other conditions potentially able to affect study subjects’ compliance;
Concomitant therapy with statins, antioxidant drugs (e.g. vitamins, Q10 coenzyme, Superoxide dismutase [SOD]), beta-blockers, non steroidal antinflammatory drugs (NSAIDS), aspirin, corticosteroids;
Known allergy, sensitivity or intolerance to study drugs and/or study drugs formulation ingredients;
Participation in another trial in the 3 months preceding study entry

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 1227 0
Italy
State/province [1] 1227 0

Funding & Sponsors
Funding source category [1] 3907 0
Commercial sector/Industry
Name [1] 3907 0
Takeda Italia Farmaceutici S.p.A.
Address [1] 3907 0
Via Elio Vittorini 129
00144 Rome, ITALY
Country [1] 3907 0
Italy
Primary sponsor type
Commercial sector/Industry
Name
Takeda Italia Farmaceutici S.p.A.
Address
Via Elio Vittorini 129
00144 Rome, ITALY
Country
Italy
Secondary sponsor category [1] 3505 0
None
Name [1] 3505 0
Address [1] 3505 0
Country [1] 3505 0

Ethics approval
Ethics application status
Approved

Summary
Brief summary
Besides its critical role in metabolic homeostasis, PPAR-gamma modulates several cellular responses involved in atherothrombosis, thus exerting a possible effect on inflammatory response of endothelium, vessel smooth muscular cells and monocytes-macrophages. These observations suggest that pioglitazone might positively influence the progression of the atherosclerotic process in diabetes and can be regarded as a new therapeutical approach to reduce cardiovascular events.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 28960 0
Address 28960 0
Country 28960 0
Phone 28960 0
Fax 28960 0
Email 28960 0
Contact person for public queries
Name 12117 0
Antonio Nicolucci
Address 12117 0
Consorzio Mario Negri Sud
Via Nazionale 8/A
66030 S. Maria Imbaro (CH), Italy
Country 12117 0
Italy
Phone 12117 0
+390872570260
Fax 12117 0
Email 12117 0
nicolucci@negrisud.it
Contact person for scientific queries
Name 3045 0
Antonio Nicolucci
Address 3045 0
Consorzio Mario Negri Sud
Via Nazionale 8/A
66030 S. Maria Imbaro (CH), Italy
Country 3045 0
Italy
Phone 3045 0
+390872570260
Fax 3045 0
Email 3045 0
nicolucci@negrisud.it

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary