Hypertension in Hemodialysis Patients (Aim 3)

• ClinicalTrials.gov Identifier: NCT00582114
• Recruitment Status: Terminated
• First Posted: December 28, 2007
• Results First Posted: January 18, 2016
• Last Update Posted: January 18, 2016
• Sponsor: Indiana University
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by (Responsible Party): Indiana University

Study Description

Brief Summary:

We will directly test the hypothesis that an initial strategy of lisinopril-based therapy will be more effective than atenolol-based therapy in causing regression of left ventricular hypertrophy (LVH) over one year in patients with hemodialysis hypertension despite similar degree of BP reduction.

Condition or disease	Intervention/treatment	Phase
Hemodialysis; Hypertension; Left Ventricular Hypertrophy	Drug: Lisinopril; Drug: Atenolol	Phase 3

Detailed Description:

This is a parallel group, active control, single-center, open-label, randomized controlled trial comparing the safety and efficacy of initial therapy with an angiotensin converting enzyme (ACE) inhibitor (lisinopril) vs. beta-blocker therapy (atenolol) each administered three times weekly after dialysis.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Hypertension in Hemodialysis Patients
• Study Start Date: August 2005
• Actual Primary Completion Date: September 2013
• Actual Study Completion Date: September 2013

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 1; Atenolol	Drug: Atenolol; Patients will be randomized into two groups, one that is beta blocker based, the other angiotensin converting enzyme (ACE) inhibitor (lisinopril) based. Patients who are on no medications will receive atenolol 25 mg. t.i.w. or lisinopril 10 mg. t.i.w. for one month at the end of which, dose will be titrated to twice the drug doses following monthly interval to another doubling of dose. If BP is still poorly controlled felodipine will be added. Other antihypertensive therapies will be added to control home BP to <140/90 mm Hg.
Experimental: 2; Lisinopril	Drug: Lisinopril; Patients will be randomized into two groups, one that is beta blocker based, the other angiotensin converting enzyme (ACE) inhibitor (lisinopril) based. Patients who are on no medications will receive atenolol 25 mg. t.i.w. or lisinopril 10 mg. t.i.w. for one month at the end of which, dose will be titrated to twice the drug doses following monthly interval to another doubling of dose. If BP is still poorly controlled felodipine will be added. Other antihypertensive therapies will be added to control home BP to <140/90 mm Hg.

Outcome Measures

Primary Outcome Measures :

1. The Primary End Point is the Regression of Left Ventricular Hypertrophy (LVH) by Echocardiographic Criteria From Baseline to 1 Year. [ Time Frame: Baseline, 6 months, 12 months ]
   The primary outcome of the study was the average reduction in left ventricular mass indexed for body surface area from baseline to 1 year. A mixed model was used with left ventricular mass index (LVMI) as the outcome variable. Fixed effects were indicator variables for time, treatment and their interaction. Random effect was subject and statistical inference was made using the maximum likelihood estimator. No imputation was made for missing data.

Other Outcome Measures:

1. Serious Adverse Events and Cardiovascular Events That Led to Trial Termination [ Time Frame: 1 yr ]
   Cardiovascular events were counted by subject and included the following: myocardial infarction (MI), stroke, hospitalization for congestive heart failure (CHF), hospitalized angina, arrhythmias, cardiac arrest, coronary revascularization and heart valve replacement. Adverse events reported are those during the course of 12 months of participation in the trial. All serious adverse events were adjudicated by R.A. and A.D.S. who were masked to the drug assignment at the time of adjudication. The duration of participation in the study per subject, which according to the trial design could be up to 12 months, was determined. The cardiovascular event rate was calculated by treatment group assignment. Incidence rate ratio (IRR) by treatment was then determined along with the 95% confidence intervals (95% CIs). As a post hoc analysis, we also determined the narrower definition of cardiovascular events per group that included MI, stroke, CHF, or cardiovascular death.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Patients on chronic hemodialysis for > 3 mos.
2. Compliance with hemodialysis treatments as defined by less than one missed dialysis per month
3. Hypertension as diagnosed by ambulatory blood pressure monitoring (ABPM) >135/75 mm Hg after participation in the ultrafiltration (UF) Trial, or those on no antihypertensive medications but unwilling to do UF Trial.
4. Presence of LVH on echocardiogram defined as left ventricular mass index (LVMi) >104 g/m2 in women and >116 g/m2 in men.
5. Willingness to give informed consent.

Exclusion criteria:

1. Vascular event (stroke, myocardial infarction or limb ischemia requiring bypass) within previous six months
2. Noncompliance with hemodialysis treatments
3. Known drug abuse
4. Chronic obstructive pulmonary disorder (COPD) requiring home oxygen
5. Congestive Heart Failure Class III or IV.
6. Body mass index > 40 kg/m2.
7. Known contraindication to atenolol (severe heart failure, bradycardia, bronchial asthma, intolerance or allergy) or lisinopril (cough, pregnancy, intolerance or allergy)

Contacts and Locations

Locations

United States, Indiana

Indiana University

Indianapolis, Indiana, United States, 46202

Sponsors and Collaborators

Indiana University

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Rajiv Agarwal, MD; Indiana University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Agarwal R, Sinha AD, Pappas MK, Abraham TN, Tegegne GG. Hypertension in hemodialysis patients treated with atenolol or lisinopril: a randomized controlled trial. Nephrol Dial Transplant. 2014 Mar;29(3):672-81. doi: 10.1093/ndt/gft515. Epub 2014 Jan 6.

• Responsible Party: Indiana University
• ClinicalTrials.gov Identifier: NCT00582114 History of Changes
• Other Study ID Numbers: 0306-13; R01DK062030 ( U.S. NIH Grant/Contract ); NIH-NIDDK-5RO1-062030
• First Posted: December 28, 2007
• Results First Posted: January 18, 2016
• Last Update Posted: January 18, 2016
• Last Verified: December 2015

Keywords provided by Indiana University:

Hemodialysis; Hypertension; Left ventricular hypertrophy

Additional relevant MeSH terms:

Atenolol; Hypertension; Hypertrophy, Left Ventricular; Hypertrophy; Vascular Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Cardiomegaly; Heart Diseases; Lisinopril; Angiotensin-Converting Enzyme Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Cardiotonic Agents; Protective Agents; Physiological Effects of Drugs; Anti-Arrhythmia Agents; Sympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic beta-1 Receptor Antagonists; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents