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

NCT01291888 | Completed

• 1 other identifier: HUM00034784
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Kidney Disease

Outcome Measures

Primary Outcomes (1)

• Primary Efficacy

  The primary efficacy variable will be the change in ADMA level from baseline to end of study.

  Baseline to End of Study

Secondary Outcomes (1)

• Secondary Efficacy

  Baseline to End of Study

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Michigan: lead
• Forest Laboratories: collaborator

Study Sites (1)

University of Michigan Health Systems

Ann Arbor, Michigan, 48109, United States

Location

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).

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Rajiv Saran, MD, MS, MRCP

  University of Michigan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MBBS, MD, MS, MRCP

Study Record Dates

• First Submitted: February 8, 2011
• First Posted: February 9, 2011
• Study Start: March 1, 2011
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: August 5, 2015

Record last verified: 2015-08

Locations

US (1)