A multi-center, randomized, double-blind, placebo-controlled clinical trial to evaluate the effect of 52 weeks treatment with vildagliptin on left ventricular function in patients with type 2 diabetes and congestive heart failure.

• Register: EUCTR
• Last refreshed on: 9 December 2013
• Main ID: EUCTR2008-005012-41-DK
• Date of registration: 14/06/2010
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A multi-center, randomized, double-blind, placebo-controlled clinical trial to evaluate the effect of 52 weeks treatment with vildagliptin on left ventricular function in patients with type 2 diabetes and congestive heart failure.
• Scientific title: A multi-center, randomized, double-blind, placebo-controlled clinical trial to evaluate the effect of 52 weeks treatment with vildagliptin on left ventricular function in patients with type 2 diabetes and congestive heart failure.
• Date of first enrolment: 24/06/2010
• Target sample size: 246
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-005012-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: Single blind: Double blind: yes Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: yes Other:

Countries of recruitment

Czech Republic, Denmark, Estonia, Germany, Greece, Italy, Latvia, Lithuania, Slovakia

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patients must give written informed consent before any assessment is performed.
2. Patients 18-85 years old (inclusive) at Visit 1.
3. Patients with T2DM, diagnosed at least 3 months prior to Visit 1, either untreated (defined as not taking anti-diabetic therapy for at least 8 weeks prior to Visit 1) or treated with anti-diabetic therapy (defined as metformin, sulfonylurea, insulin, alpha-glucosidase inhibitors, or glinides as monotherapy or combination therapy for at least 8 weeks prior to Visit 1) and maintaining dietary advice and exercise habits during the full course of the study.
4. Stable dose of anti-diabetic therapy over the past 4 weeks prior to Visit 1 (stable insulin therapy is defined as ± 20% of total daily units) for patients on anti-diabetic treatment.
5. CHF (NYHA Class I, Class II, or Class III) at Visit 1.
• Treatment of heart failure should be according to local/national guidelines [ACC/AHA 2005], [ESC/EASD 2007] and dosage of beta-blockers, angiotensin converting enzyme-inhibitors(ACE-Is) or angiotensin receptor blockers (ARBs) should have been stable for one month prior to visit 1.
6. LVEF < 40% (results must be available at Visit 2, prior to randomization)
7. HbA1c in the range of = 6.5% to 10% at Visit 1.
8. Body Mass Index (BMI) in the range of 22-42 kg/m2, inclusive, at Visit 1.

For detailed inclusion criteria, please refer to the full protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Fasting Plasma Glucose (FPG) = 270 mg/dL (15 mmol/L) at Visit 1.
2. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL).
3. A history of:
• type 1 diabetes, diabetes that is a result of pancreatic injury, or secondary forms of diabetes, e.g. Cushing’s syndrome and acromegaly.
• acute metabolic diabetic complications such as ketoacidosis or hyperosmolar state (coma) within the past 6 months.
4. Patients that have been enrolled in a vildagliptin clinical trial or taken other DPP-4 inhibitor, GLP-1 mimetics (e.g. exenatide), GLP-1 analogues (e.g. liraglutide) studies within 6 months prior to visit 1.
5. Patients taking vildagliptin at any time.
6. Patients taking thiazolidinediones (TZDs). TZDs given up to 6 months prior to Visit 1 are allowed.
7. Acute infections which may affect blood glucose control within 4 weeks prior to visit 1 and other concurrent medical condition that may interfere with the interpretation of efficacy and safety data during the study
8. Any of the following within the past 6 months:
• myocardial infarction (MI) (if the visit 1 ECG reveals patterns consistent with a MI and the date of the event cannot be determined, then the patient can enter the study at the discretion of the investigator and the sponsor);
• coronary artery bypass surgery or percutaneous coronary intervention
• unstable angina
• stroke
9. Any of the following ECG abnormalities:
• Torsades de pointes, sustained and clinically relevant ventricular tachycardia or ventricular fibrillation
• second degree AV block (Mobitz 1 and 2); patients with pacemakers are not excluded.
• third degree AV block; patients with pacemakers are not excluded.
• prolonged QTc (> 500 ms) per Bazett´s method.
10. GFR (estimated by Cockcroft-Gault formula) < 30 mL/min at Visit 1.

For detailed exclusion criteria, please refer to the full protocol.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Type 2 Diabetes

Intervention(s)

Trade Name: Galvus
Product Name: vildagliptin
Product Code: LAF237
Pharmaceutical Form: Tablet
INN or Proposed INN: vildagliptin
Current Sponsor code: LAF237A
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: • To evaluate the effect of vildagliptin on left ventricular function in patients with T2DM and CHF (NYHA class I-III) by showing that vildagliptin is at least not inferior to placebo with respect to change in left ventricular ejection fraction (LVEF) after 52 weeks of treatment.

Primary end point(s): The primary outcome variable is change from baseline in LVEF (%) at Week 52, regardless of rescue medication use. Baseline is the measurement obtained on the day of Screening (Week -2, Visit 1).

Secondary Objective: • To evaluate the overall safety and tolerability of vildagliptin versus placebo in patients with T2DM and CHF (NYHA class I – III) over 52 weeks of treatment with special regards to signs and symptoms of heart failure.
• To evaluate the efficacy of vildagliptin in patients with T2DM and CHF (NYHA class I-III) by assessing the HbA1c reduction with vildagliptin compared to placebo after 16 weeks of treatment.

Secondary ID(s)

CLAF237A23118

2008-005012-41-CZ