The main objective is to illuminate the effect of S 44121 (restores the Ca²+ release channel function by improving the rebinding of the channel-stabilizing subunit (calstabin)) versus placebo administered orally for a total of 12 weeks on MTWA in…
ID
Source
Brief title
Condition
- Heart failures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Alteration in presence or absence of MTWA before and after drug admission.
Secondary outcome
na
Background summary
The risk of sudden cardiac death (SCD) is increased among patients with reduced
left ventricular (LV) function. An electrocardiographic marker, the microvolt
T wave alternans (MTWA) has been approved for cardiovascular risk
stratification in heart failure patients. Changes in membrane voltage (V m),
caused by steep action potential duration (APD) restitution, or - alternatively
- from Ca 2+ cycling dynamics have been suggested as underlying cellular
mechanisms causing MTWA, but definitive proof is lacking.
Presumably, the alteration of the Ca²+ transient reflect an alternation of the
release of Ca²+ from the sarcoplasmatic reticulum (SR). Given that electrical
alternans in ventricular muscle is eliminated by all interventions that abolish
mechanical alternans (e.g. ryanodine and caffeine), it would appear that
mechanical alternans is responsible for electrical alternans. Therefore this
study will focus on the Ca2+ cycling dynamics where S 44121 will offer us a
unique possibility to study the effect of this drug on calcium cycling dynamics
and therefore its effect on MTWA.
Study objective
The main objective is to illuminate the effect of S 44121 (restores the Ca²+
release channel function by improving the rebinding of the channel-stabilizing
subunit (calstabin)) versus placebo administered orally for a total of 12 weeks
on MTWA in patients with chronic heart failure (CHF) and left ventricular
systolic dysfunction who received an implanted cardioverter defibrillator (ICD)
for primary or secondary prevention of ventricular arrhythmia.
Study design
This is an observational study. After obtaining informed consent MTWA will be
measured after the required heart rate is reached before and 12-14 weeks after
administration of the S 44121 or placebo.
Study burden and risks
The MTWA recordings are non invasive and take maximally 20 minutes extra time.
There is no extra risk or benefit to the patients in participating in this
study.
Meibergdreef 9
1105 AZ Amsterdam
NL
Meibergdreef 9
1105 AZ Amsterdam
NL
Listed location countries
Age
Inclusion criteria
-Male or female, Aged >=18 years and<= 85 years
-Received an lCD for primary or secondary prevention of ventricular arrhythmia at least 3 months
before selection,
-Symptomatic chronic heart failure for at least 6 months before selection,
-NYHA functional class I, II or Ill,
-Stable condition with regards to heart failure symptoms for at least 4 weeks before selection,
-Ischemic disease or idiopathic dilated cardiomyopathy as main cause for CHF,
-Treated with optimal and unchanged CHF treatment and dosages for at least 4 weeks before
selection,
-Treated with a maximal tolerated dosis beta-blocker for at least 3 months before selection
(Patient can receive less than the daily target dose of the bela-blocker recommended in the ESC
guidelines 2008)
- Regular sinusal or atrial rhythm, paced or spontaneous, and provided that atrial contraction
preceeds ventricular contraction
Exclusion criteria
-Women who are pregnant,
-Women who are breast·feeding,
-Women of childbearing potential not using estro-progestative or progestative or intra-uterine
contraception, or women using estro-progestative or progestative or intra-uterine contraception,
but who consider stopping it during the planned duration of the study,
-Participation in another drug or device trial at the same time or during the 30 days prior to
selection. Marketed drugs used for unapproved indications are considered to be investigational
drugs,
-Unstable condition within the previous 4 weeks before selection (e.g. documented hospital
admission due to worsening of chronic heart failure)
-Recent (less than 3 months before selection): myocardial infarction, unstable angina, coronary
revascularisation,cerebral stroke or TIA
- Severe valvular disease, congenital heart disease or pericardia! disease,
-Scheduled surgery for valvular heart disease, for revascularisation (PC I or CABG),
-Jntracardiac thrombus,
-Active myocarditis,
-Previous cardiac transplantation or on Jist for cardiac transplantation,
-Cardiac resynchronisation therapy (CRT) started within the previous 3 months before selection,
-Change in the anti-arrhythmic treatment or dose within the previous 4 weeks before selection,
-Episode of reverted ventricular fibrillation or Torsade de Pointes in the last 4 weeks,
-History of cardioversion or ablation for to treat atrial fibrillation or ventricular tachycardia in the
previous 3 months before selection,
-Atrio-ventricular block of second or third degree (documented on a resting ECG),
-Corrected QT interval duration (Bazett's formula) > 480 ms,
·Family history of long QT syndrome or congenital long QT syndrome,
-INR < 1.4 or > 3.4 in patients taking anti-vitamin K oral anticoagulation,
-Severe or uncontrolled hypertension (systolic blood pressure> 180 mmHg or diastolic blood
pressure> 110 mmHg),
-Unstable clinical condition or change in the CHF or anti-arrhythmic treatment or dosage since the
selection visit,
- Biological parameters: Sodium or Potassium out of range, creatinine > 200 ~molll, ALA T and/or
ASAT > x3 ULN
-Systolic blood pressure < 90 mmHg
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL37991.018.11 |