Nebivolol Versus Sustained Release Metoprolol Succinate in Patients With Chronic Kidney Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01291888
Recruitment Status : Completed
First Posted : February 9, 2011
Last Update Posted : August 5, 2015
Forest Laboratories
Information provided by (Responsible Party):
Rajiv Saran, University of Michigan

Brief Summary:

The investigators postulate that nebivolol will be more effective than an equivalent dose of a comparative BB, specifically sustained release metoprolol succinate, in improving the availability of NO, lowering blood pressure, and reducing albuminuria with implications for slowing progression of CKD and cardiovascular protection in this high risk population.

The objective of this proposal is to conduct a randomized pilot clinical trial to determine the relative efficacy and tolerability of nebivolol versus sustained release metoprolol succinate in improving blood pressure in patients with CKD and albuminuria. The primary endpoint would be a decrease in asymmetric dimethyl arginine (ADMA). Secondary endpoints would include a reduction in blood pressure, urinary F2-isoprostanes and albuminuria.

Condition or disease
Chronic Kidney Disease

  Show Detailed Description

Study Type : Observational
Actual Enrollment : 50 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Efficacy and Tolerability of Nebivolol Versus Sustained Release Metoprolol Succinate in Patients With Chronic Kidney Disease: A Single-center Randomized Trial.
Study Start Date : March 2011
Actual Primary Completion Date : January 2014
Actual Study Completion Date : January 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Diseases
U.S. FDA Resources

Primary Outcome Measures :
  1. Primary Efficacy [ Time Frame: Baseline to End of Study ]
    The primary efficacy variable will be the change in ADMA level from baseline to end of study.

Secondary Outcome Measures :
  1. Secondary Efficacy [ Time Frame: Baseline to End of Study ]
    Secondary efficacy parameters will include: the change in blood pressure, GFR, urinary albumin excretion, and biomarkers including urinary F2-Isoprostanes, BNP, hsCRP, Cystatin C, and a measure of insulin resistance-the homeostatic model assessment (HOMA) from baseline to end of study

Biospecimen Retention:   Samples Without DNA
A total of 30 ml blood (CBC with differential and platelets-3ml, comprehensive panel-5-7ml, biomarkers-20ml) will be drawn by venipuncture typically from the antecubital vein at baseline visit (30ml), and week 6-study midpoint (30ml) and end of study (30ml). At the screening visit only 10ml blood will be required (CBC and Comprehensive Panel).

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
A total of 50 patients with CKD meeting the inclusion and exclusion criteria listed below will after informed consent be randomized to either nebivolol or sustained release metoprolol succinate and followed for 3 months or early termination of the study.

Inclusion Criteria:

  • Age > 18 years old and < 85 years old
  • Willing and able to comply with all study procedures
  • Blood pressure on standard antihypertensive therapy, which may include: a diuretic, ACE-I, ARB, CCB, and/or an alpha adrenergic antagonist, and a blood pressure ≤ 180 mm Hg systolic and ≥ 130 mm Hg systolic. The blood pressure will be taken after a period of 15 minutes of resting in the sitting posture
  • Clinically stable patients with CKD (GFR 20-60 ml/min/1.73 m²) by the abbreviated MDRD equation and with a rate of decline of GFR no greater than 1 ml/min/1.73 m² per month over the prior three months and with albuminuria (urine albumin:creatinine ratio) in a spot urine sample of between 100-3000 mcg/g of creatinine). Albumin excretion (i.e., urine albumin:creatinine ratio) will be checked prior to enrollment in two separate (collected at least one week apart) spot early morning urine specimens
  • Females of child bearing potential must have a negative pregnancy test at screening. Females considered not of childbearing potential include those who have been in menopause at least 2 years, had tubal ligation at least 1 year prior to screening or who have had a total hysterectomy

Exclusion Criteria:

  • Use of a BB in the 3 months prior to study enrollment, other than atenolol or metoprolol
  • Uncontrolled hypertension with a blood pressure > 160/100 mm Hg or those with changes to their antihypertensive regime during the last 2 months
  • Concurrent disease or conditions that would interfere with study participation or safety, such as bleeding disorders, history of syncope or vertigo, severe gastrointestinal reflux (GERD) or gastric ulcers, heart failure, symptomatic coronary or peripheral vascular disease, arrhythmia, serious neurological disorders including seizures or organ transplantation
  • Diabetics that are uncontrolled (HbA1c consistently > 9.0 g/dL), unstable, newly diagnosed, or have undergone major changes in therapy within the last 2 months
  • Any severe co-morbid condition that would limit life expectancy to < 6 months
  • Advanced CKD with an eGFR < 20 ml/min/1.73 m²
  • Patients with albuminuria due to causes other than diabetes mellitus or hypertension
  • Hepatic enzyme concentrations > 2 times the upper limit of normal
  • HIV infection, hepatic cirrhosis or other preexisting liver disease; or positive HIV, Hepatitis B or C test at screening
  • Use of any investigational product or investigational medical device within the last 60 days of screening
  • History of alcohol and or drug abuse
  • Any condition that in view of the investigators places the subject at high risk of poor treatment or compliance or of not completing the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01291888

United States, Michigan
University of Michigan Health Systems
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
University of Michigan
Forest Laboratories
Principal Investigator: Rajiv Saran, MD, MS, MRCP University of Michigan

Responsible Party: Rajiv Saran, MBBS, MD, MS, MRCP, University of Michigan Identifier: NCT01291888     History of Changes
Other Study ID Numbers: HUM00034784
First Posted: February 9, 2011    Key Record Dates
Last Update Posted: August 5, 2015
Last Verified: August 2015

Additional relevant MeSH terms:
Kidney Diseases
Renal Insufficiency, Chronic
Urologic Diseases
Renal Insufficiency
Anti-Arrhythmia Agents
Antihypertensive Agents
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
Vasodilator Agents
Adrenergic beta-1 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists