Sunitinib and Atrial Trabeculae Contractility (SCAR)

Radboud University Medical Center

Status: Completed

Conditions: Cardiotoxicity; Ischemia; Heart Failure

Study type: Observational

Funder types: Other

Identifiers

NCT01246778

SCAR

Details and patient eligibility

About

Rationale:

Recently, sunitinib (a tyrosine kinase inhibitor that is used for treatment of metastatic renal carcinoma and gastrointestinal stroma tumors) has been associated with development of heart failure, possibly by off-target inhibition of AMP-protein kinase. The investigators hypothesize that sunitinib reduces the contractile ability of myocardium and the tolerance against ischemia-reperfusion and that activators of AMP-protein kinase such as atorvastatin and AICAR reverse this unwanted effect of sunitinib.

Objectives:

The primary objective of the study is to investigate the effect of sunitinib on ex-vivo atrial contractile force in absence and presence of ischemia-reperfusion.

A secondary objective is to explore if atorvastatin or AICAR prevent sunitinib-induced deterioration of contractile function of human atrial trabeculas. Study design: Lab

Full description

Study population: 44 (+22) patients undergoing CABG cardiac surgery with extracorporal circulation Intervention (if applicable): none (pharmacological interventions will only be performed ex-vivo in isolated atrial tissue) Main study parameters/endpoints The developed force in ex vivo atrial trabeculas during standardized stimulation.

Enrollment: 20 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Cardiac surgery with extracorporal circulation

Exclusion criteria

• Use of oral antiarrhythmics
• theophylline use
• Use of sulfonylureas
• Atrial arrythmias
• Right ventricular failure

Trial design

20 participants in 2 patient groups

With/without sunitinib

Description:

Two trabeculas will be isolated and one will be exposed to sunitinib and the other to normal buffer solution. Both will be stimulated to contraction during 200 minutes.

With/without sunitinib IP

Description:

Two trabeculas will be isolated and one will be exposed to sunitinib and the other to normal buffer solution. Both will be stimulated to contraction and ischemia/reperfusion