Candesartan added” therapy for treatment optimization of symptomatic heart failure with diastolic dysfunction in diabetic and hypertensive patients. A randomized, placebo-controlled, double-blind, parallel-group and multicentre clinical phase III study investigating the effects on NT-proBNP over 6 months. - CAN-DHF

• Conditions: Symptomatic heart failure with diastolic dysfunction in diabetic and hypertensive patients; MedDRA version: 9.1Level: LLTClassification code 10019279Term: Heart failure; MedDRA version: 9.1Level: LLTClassification code 10052337Term: Diastolic dysfunction

• Registration Number: EUCTR2007-003070-26-DE
• Lead Sponsor: Takeda Pharma GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-07-10
• Last Update Posted: 9 October 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

- Male or female patient of at least 45 years of age
- Diabetes mellitus type 2 - insulin dependent or orally treated or managed by diet for at least
3 months
- Normotension or controlled hypertension with sSBP < 140 mmHg and/or sDBP < 90 mmHg
- Regular sinus rhythm or atrial fibrillation with a medicamentally achieved rate control of less
than 100 bpm as confirmed by ECG-recordings (see also additional criteria 4.4)
- Echocardiographic evidence of a preserved LVEF = 45% (assessed by the modified Simpson-
method) with further doppler-echocardiographic criteria for diastolic dysfunction grade I-IV.
Each grade must be confirmed by 3 of the following 5 parameters
(validated for sinus rhythm):
Grade E/A DT S/D E/E’ VP_
Impaired relaxation (I) =0,75 >220 >1 <10 >45
Pseudonormalisation (II) 0,75-1, 5 150-220 <1 =10 <45
Restrictive filling (III/IV*) >1,5 =150 <<1 =10 <45
* The lack of E/A- reversibility under valsalva manoeuvre connotes grade IV

- NYHA-classification of II or III in a stable condition since at least 3 months
- Existing background HF-therapy with an ACEI alone or together with further preparations in a
constant regimen since at least 1 month, in case of ß-blockers since at least 3 months
- NT-proBNP = 220 pg/ml measured at screening visit or collected from a dated previous
laboratory document not older than 3 months
- No previous therapy with ARBs during the last 4 weeks prior to the study
- A woman of childbearing potential must have a negative pregnancy test before study start
and must plan not to become pregnant during the study
- A woman of non-childbearing potential can be included if she was surgically sterilized or
hysterectomized at least three months before study start or when the postmenopausal status
was confirmed by a period of amenorrhoe of at least 12 months plus concomitant adequate
hormone levels (i.e., FSH > 40 MIE/ml and estrogen < 30 pg/ml or negative estrogen test)
- Available signed written informed consent

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

The following criteria must not be met to enrol a single patient into the study:
- Impaired renal function (serum creatinine > 2.2 mg/dl or > 194 µmol/l)
- Known bilateral renal artery stenosis (RAS) or interventional treatment for RAS in the last year
- State after kidney transplantation
- Serum potassium > 5.5 mmol/l or HbA1C > 9.5 %
- Cor pulmonale or primary pulmonary disease with dyspnea at rest
- Known disposition to episodes of symptomatic hypotension or sSBP < 95 mmHg at baseline
- Acute coronary syndrome or unstable angina pectoris and any coronary artery disease that
was not stable during the last 3 months prior to inclusion
- CABG or PTCA (incl. stent implantation) within 3 months before inclusion
- Myocardial infarction or stroke within 6 months before inclusion
- Patients who are dependent on a permanently paced pacemaker (i.e. a patient with a device
that is not pacing during the echocardiographic examination can enter the study)
- Open heart surgery for other reasons than coronary revascularization
- Tachycardia at rest > 100 bpm as confirmed by ECG-recordings
- Known clinically relevant rhythm disorders (e.g., tachyarrhythmias, salves of supraventricular
or ventricular extrasystoles or atrial fibrillation without ventricular rate control) or symptoms
suggesting a significant rhythm disorder (e.g., recurrent syncopes)
- Primary valvular diseases and/or restrictive or obstructive cardiomyopathy
- Existing ventricular assist devices
- Relevant liver diseases (cholestasis or ALAT/ASAT > 2xULN or ?GT > 3xULN)
- History of primary hyperaldosteronism, of cancer in the last 5 years (exception: non-
metastasizing skin cancer) or of another wasting disease with life expectancy of < 2 years
- Known hypersensitivity to Candesartan Cilexetil
- Need for maintenance therapy with NSAIDs or Cox-2-inhibitors
- Use of other ARBs throughout the entire study period
- Any history of life-threatening diseases
- History of drug addiction and/or an extensive use of alcohol
- Female patients who are pregnant or breast feeding
- Sexually active women of childbearing potential not consistently and correctly practicing
highly effective birth control with a low failure rate (less than 1% / year) such as implants,
injectables, combined oral contraceptives, hormonal intrauterine devices (IUDs), sexual
abstinence or vasectomised partner
- Psychological and/or emotional problems, which render the informed consent invalid or limit
the ability of the patient to comply with the study requirements
- Patient is an employee or at least in dependence of the investigator and/or the sponsor or of
another institution directly involved in the study or other trials under the investigator's direction
- Participation in another clinical investigation within 30 days prior to enrolment or for the course
of the present study (incl. studies for compassionate use or experimental medical devices)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified