Hypertension in Hemodialysis Patients (Aim 3)

This study has been terminated.
(Stopped by data safety monitoring board)
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Indiana University
ClinicalTrials.gov Identifier:
NCT00582114
First received: December 20, 2007
Last updated: December 14, 2015
Last verified: December 2015
  Purpose
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 Intervention Phase
Hemodialysis
Hypertension
Left Ventricular Hypertrophy
Drug: Lisinopril
Drug: Atenolol
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Hypertension in Hemodialysis Patients

Resource links provided by NLM:


Further study details as provided by Indiana University:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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:
  • Serious Adverse Events and Cardiovascular Events That Led to Trial Termination [ Time Frame: 1 yr ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 200
Study Start Date: August 2005
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00582114

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):
Responsible Party: Indiana University
ClinicalTrials.gov Identifier: NCT00582114     History of Changes
Other Study ID Numbers: 0306-13  R01DK062030  NIH-NIDDK-5RO1-062030 
Study First Received: December 20, 2007
Results First Received: October 5, 2015
Last Updated: December 14, 2015
Health Authority: United States: Federal Government

Keywords provided by Indiana University:
Hemodialysis
Hypertension
Left ventricular hypertrophy

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

ClinicalTrials.gov processed this record on July 24, 2016