Clinical trial NCT01805804: Valsartan to Prevent Left Ventricle Remodeling in Pacemaker Patients
Official title: Randomized, Placebo Controlled Blinded Study to Assess the Efficacy of Valsartan to Prevent Left Ventricle Remodeling in Patients With Dual Chamber Pacemaker
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: First Time Dual Chamber Pacemaker Implantation
Keywords: dual chamber pacing, left ventricle remodeling, valsartan
Lead sponsor: Medical University of Silesia
Sponsor class: OTHER
Collaborators: name: Polpharma Pharmaceutical Company
First posted: 2013-03-06
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Dual chamber pacing is known to induce left ventricle remodeling and may eventually lead to heart failure. The investigators aim to test hypothesis that valsartan started immediately after dual chamber pacemaker implantation will prevent left ventricle remodeling in twelve months long follow up in comparison with placebo. Echocardiographic assessment of left ventricle remodeling will be correlated with plasma activity of matrix metalloproteinases and their tissue inhibitors, indices of functional capacity such as plasma level of NTproBNP and distance in meters during six minute walking test.


Eligibility criteria: Inclusion Criteria:

* informed written consent
* age ≥ 18 years
* first time pacemaker implantation for trifascicular block, atrioventricular second or third degree block
* left ventricle ejection fraction ≥ 40%

Exclusion Criteria:

* significant valvular heart disease
* ischaemic heart disease requiring further revascularization
* symptomatic hypotension
* orthostatic disorders
* pregnancy, breast feeding, child bearing potential
* previous use of angiotensin receptor blocking agents
* known hypersensitivity to valsartan
* significant liver disorders
* significant renal disorders, including renal artery stenosis
* hyperaldosteronism
* chronic use of nonsteroid antiinflammatory drugs
* chronic use of lithium salts
* Patient's reluctance or disability to obey protocol and/or follow the scheduled visits
* any significant disease to reduce the expected life duration \< 12 months
* participation in any other trial within the last 30 days before randomization
* any situation that would put more risk on patient

Primary outcomes:
measure: change in echocardiographically assessed left ventricle dimensions and left ventricle function
timeFrame: baseline and 12 months
Secondary outcomes:
measure: change in plasma level of matrix metalloproteinase 9
timeFrame: baseline and 12 months
measure: change in plasma level of NTproBNP
timeFrame: baseline and 12 months
measure: change in atrial arrhythmia burden assessed from pacemaker memory
timeFrame: baseline and 12 months
measure: change in the rate of occurrence of any major adverse cardiovascular event
timeFrame: 2 weeks, 3 months, 6 months, 9 months and 12 months
measure: change in plasma level of tissue necrosis factor alpha
timeFrame: baseline and 12 months
measure: change in plasma level of tissue inhibitor of matrix metalloproteinase 3
timeFrame: baseline and 12 months
measure: change in distance walked during six minute walking test
timeFrame: baseline and 12 months
Other outcomes:
Locations:
city: Zabrze
country: Poland
facility: II Dept. of Cardiology in Zabrze Medical University of Silesia
state: Upper Silesia
Study officials:
affiliation: Medical University of Silesia
name: Ewa Nowalany-Kozielska, MD PhD Associate Professor
role: STUDY_DIRECTOR
References:
citation: Suzuki H, Geshi E, Nanjyo S, Nakano H, Yamazaki J, Sato N, Tanaka K, Takano T, Yagi H, Shibata T, Mochizuki S, Katagiri T. Inhibitory effect of valsartan against progression of left ventricular dysfunction after myocardial infarction: T-VENTURE study. Circ J. 2009 May;73(5):918-24. doi: 10.1253/circj.cj-08-0959. Epub 2009 Apr 2.
citation: Miyazaki S, Kasai T, Miyauchi K, Miyazaki T, Akimoto Y, Takagi A, Aihara K, Kawamura M, Suwa S, Kojima S, Sumiyoshi M, Daida H. Changes of matrix metalloproteinase-9 level is associated with left ventricular remodeling following acute myocardial infarction among patients treated with trandolapril, valsartan or both. Circ J. 2010 Jun;74(6):1158-64. doi: 10.1253/circj.cj-09-0412. Epub 2010 Apr 6.
citation: Garcia RA, Brown KL, Pavelec RS, Go KV, Covell JW, Villarreal FJ. Abnormal cardiac wall motion and early matrix metalloproteinase activity. Am J Physiol Heart Circ Physiol. 2005 Mar;288(3):H1080-7. doi: 10.1152/ajpheart.00860.2004. Epub 2004 Oct 14.
citation: Tomasik A, Jachec W, Wojciechowska C, Kawecki D, Bialkowska B, Romuk E, Gabrysiak A, Birkner E, Kalarus Z, Nowalany-Kozielska E. Randomized placebo controlled blinded study to assess valsartan efficacy in preventing left ventricle remodeling in patients with dual chamber pacemaker--Rationale and design of the trial. Contemp Clin Trials. 2015 May;42:239-43. doi: 10.1016/j.cct.2015.03.015. Epub 2015 Apr 7.