Hypertension in Hemodialysis Patients (Aim 3)
Primary Purpose
Hemodialysis, Hypertension, Left Ventricular Hypertrophy
Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Lisinopril
Atenolol
Sponsored by
About this trial
This is an interventional treatment trial for Hemodialysis focused on measuring Hemodialysis, Hypertension, Left ventricular hypertrophy
Eligibility Criteria
Inclusion Criteria:
- Patients on chronic hemodialysis for > 3 mos.
- Compliance with hemodialysis treatments as defined by less than one missed dialysis per month
- 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.
- Presence of LVH on echocardiogram defined as left ventricular mass index (LVMi) >104 g/m2 in women and >116 g/m2 in men.
- Willingness to give informed consent.
Exclusion criteria:
- Vascular event (stroke, myocardial infarction or limb ischemia requiring bypass) within previous six months
- Noncompliance with hemodialysis treatments
- Known drug abuse
- Chronic obstructive pulmonary disorder (COPD) requiring home oxygen
- Congestive Heart Failure Class III or IV.
- Body mass index > 40 kg/m2.
- Known contraindication to atenolol (severe heart failure, bradycardia, bronchial asthma, intolerance or allergy) or lisinopril (cough, pregnancy, intolerance or allergy)
Sites / Locations
- Indiana University
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
1
2
Arm Description
Atenolol
Lisinopril
Outcomes
Primary Outcome Measures
The Primary End Point is the Regression of Left Ventricular Hypertrophy (LVH) by Echocardiographic Criteria From Baseline to 1 Year.
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT00582114
First Posted
December 20, 2007
Last Updated
December 14, 2015
Sponsor
Indiana University
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1. Study Identification
Unique Protocol Identification Number
NCT00582114
Brief Title
Hypertension in Hemodialysis Patients (Aim 3)
Official Title
Hypertension in Hemodialysis Patients
Study Type
Interventional
2. Study Status
Record Verification Date
December 2015
Overall Recruitment Status
Terminated
Why Stopped
Stopped by data safety monitoring board
Study Start Date
August 2005 (undefined)
Primary Completion Date
September 2013 (Actual)
Study Completion Date
September 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Indiana University
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
4. Oversight
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemodialysis, Hypertension, Left Ventricular Hypertrophy
Keywords
Hemodialysis, Hypertension, Left ventricular hypertrophy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
200 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Active Comparator
Arm Description
Atenolol
Arm Title
2
Arm Type
Experimental
Arm Description
Lisinopril
Intervention Type
Drug
Intervention Name(s)
Lisinopril
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Atenolol
Intervention Description
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.
Primary Outcome Measure Information:
Title
The Primary End Point is the Regression of Left Ventricular Hypertrophy (LVH) by Echocardiographic Criteria From Baseline to 1 Year.
Description
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.
Time Frame
Baseline, 6 months, 12 months
Other Pre-specified Outcome Measures:
Title
Serious Adverse Events and Cardiovascular Events That Led to Trial Termination
Description
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.
Time Frame
1 yr
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients on chronic hemodialysis for > 3 mos.
Compliance with hemodialysis treatments as defined by less than one missed dialysis per month
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.
Presence of LVH on echocardiogram defined as left ventricular mass index (LVMi) >104 g/m2 in women and >116 g/m2 in men.
Willingness to give informed consent.
Exclusion criteria:
Vascular event (stroke, myocardial infarction or limb ischemia requiring bypass) within previous six months
Noncompliance with hemodialysis treatments
Known drug abuse
Chronic obstructive pulmonary disorder (COPD) requiring home oxygen
Congestive Heart Failure Class III or IV.
Body mass index > 40 kg/m2.
Known contraindication to atenolol (severe heart failure, bradycardia, bronchial asthma, intolerance or allergy) or lisinopril (cough, pregnancy, intolerance or allergy)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rajiv Agarwal, MD
Organizational Affiliation
Indiana University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
24398888
Citation
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.
Results Reference
derived
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Hypertension in Hemodialysis Patients (Aim 3)
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