Hypertension, Transplant; Failure, Kidney
Conditions
Keywords
kidney, transplant, hypertension, nebivolol, metoprolol, bystolic, toprol
Brief summary
In an open label analysis, nebivolol has been shown to have a positive impact on quality of life in the general hypertensive population. That is, patients treated with nebivolol reported less side effects compared to those treated with metoprolol. Also, more nebivolol treated patients reached normalization of blood pressure. Although there is no data, it is believed that the impact would be similar in renal transplant recipients. The primary goal of this study is to determine if nebivolol will improve the quality of life measurements of kidney transplant recipients as compared to those treated with metoprolol succinate. This will be measured by comparing the scores of four quality of life questionnaires taken before and after 12 weeks of treatment with study drug. Other aims of this study are to determine if the use of nebivolol is cost-effective in the renal transplant recipient; determine if there is a change in urine protein excretion and renal function with the use of nebivolol; and determine the number of patients that maintain or achieve a target blood pressure of ≤ 120/80 mmHg.
Interventions
DRUGNebivolol
Subject will take nebivolol daily for 12 weeks.
DRUGMetoprolol succinate
Subject will take metoprolol succinate daily for 12 weeks.
Sponsors
Forest Laboratories
Lahey Clinic
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Adult renal transplant recipients, men and women between 18 and 75 years of age, inclusive. * Patients must be \> 3 months post-transplant. * Patients must have stable renal function (stable renal function will be defined as those patients without infection or hospitalization \[for any reason\] over the past 30 days, and patients with \< 20% change in their serum creatinine over the past 30 days. * Patients receiving corticosteroids must be receiving a daily dose of \< 7.5 mg of prednisone (or therapeutic equivalents based on glucocorticoid equivalency scale). * All eligible patients must be receiving antihypertensive medication management which must include metoprolol tartrate or metoprolol succinate. * Patients may be on more than one medication to control their hypertension. Use of any other FDA-approved antihypertensive agent is permitted. * All eligible patients will either be at goal blood pressure (\<120/80 mmHg) or have Pre-hypertension (\<140/90 mmHg) or Stage I hypertension (\<160/100 mmHg) at the time of study inclusion. * Patients who are able to comprehend and satisfactorily comply with protocol requirements. * Patients who signed the written informed consent given prior to entering any study procedure.
Exclusion criteria
* Patients with Stage II/uncontrolled hypertension (\>159/99 mmHg). * Patients with an easily identifiable etiology for fatigue (i.e. anemia, iron-deficiency, poor sleep patterns, etc.). * Patients who have a medical condition that, in the Investigator's opinion, would expose them to an increased risk of a significant adverse event or interfere with assessments of safety and efficacy during the course of the trial (i.e. arrhythmia). * Patients with any current malignancy, or any clinically significant hematological, endocrine, cardiovascular, hepatic, gastrointestinal or neurological disease (including any form of epilepsy). If there is a history of such disease but the condition has been stable for at least the past year and is judged by the investigator not to interfere with the patient's participation in the study, the patient may be included. * Patients who are judged by the investigator to be unable or unlikely to follow the study protocol and complete all scheduled visits. * Patients with any contraindications to beta blocker therapy as listed in the package labeling for both metoprolol succinate and nebivolol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life | 12 weeks; Baseline scores were measured at the Initial Screening/Enrollment Visit (Visit 1 - beginning of week 1); Follow-Up scores were measured at the End of the Study (Visit 2 - End of week 12) | Primary outcome measure will be the change from the Screening/Enrollment Visit to the End of the Study/Early Termination visit in scores of four quality of life questionnaires. The four quality of life questionnaires that were used included the following: 1. Short Form (SF)-36v2 Health Survey (Score Range = 0-100; the lower the score the more disability) 2. Sexual Dysfunction Tool for Men = International Index of Erectile Function (IIEF) Questionnaire (Score Range = 5-25; a score of 22-25 = No erectile dysfunction; 17-21 = Mild erectile dysfunction; 12-16 = Mild to moderate erectile dysfunction; 8-11 = Moderate erectile dysfunction; 5-7 = Severe erectile dysfunction) 3. Sexual Dysfunction Tool for Women = Changes in Sexual Functioning Questionnaire (CSFQ-14-F; Score Range = 14-70; a score at or below 42 is indicative of sexual dysfunction) 4. Multidimensional Assessment of Fatigue (MAF) Scale (Score Range = 1-50; the higher the score the more fatigue) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Blood Pressure | 12 weeks | Evaluate the baseline and follow-up systolic and diastolic blood pressures for all subjects in both groups. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nebivolol Nebivolol: Subject will take nebivolol daily for 12 weeks. | 6 |
| Metoprolol Succinate Metoprolol succinate: Subject will take metoprolol succinate daily for 12 weeks. | 5 |
| Total | 11 |
Baseline characteristics
| Characteristic | Nebivolol | Metoprolol Succinate | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 5 Participants | 11 Participants |
| Region of Enrollment United States | 6 participants | 5 participants | 11 participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 6 | 0 / 5 |
| serious Total, serious adverse events | 0 / 6 | 0 / 5 |
Outcome results
Primary
Quality of Life
Primary outcome measure will be the change from the Screening/Enrollment Visit to the End of the Study/Early Termination visit in scores of four quality of life questionnaires. The four quality of life questionnaires that were used included the following: 1. Short Form (SF)-36v2 Health Survey (Score Range = 0-100; the lower the score the more disability) 2. Sexual Dysfunction Tool for Men = International Index of Erectile Function (IIEF) Questionnaire (Score Range = 5-25; a score of 22-25 = No erectile dysfunction; 17-21 = Mild erectile dysfunction; 12-16 = Mild to moderate erectile dysfunction; 8-11 = Moderate erectile dysfunction; 5-7 = Severe erectile dysfunction) 3. Sexual Dysfunction Tool for Women = Changes in Sexual Functioning Questionnaire (CSFQ-14-F; Score Range = 14-70; a score at or below 42 is indicative of sexual dysfunction) 4. Multidimensional Assessment of Fatigue (MAF) Scale (Score Range = 1-50; the higher the score the more fatigue)
Time frame: 12 weeks; Baseline scores were measured at the Initial Screening/Enrollment Visit (Visit 1 - beginning of week 1); Follow-Up scores were measured at the End of the Study (Visit 2 - End of week 12)
Population: Adult (\>18 years of age) renal transplant recipients, both men and women, requiring pharmacotherapy for high blood pressure were evaluated for inclusion in this analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nebivolol | Quality of Life | Baseline SF-36 (mental) Score | 40.6 units on a scale | Standard Deviation 12 |
| Nebivolol | Quality of Life | Baseline MAF Score | 27.7 units on a scale | Standard Deviation 8.3 |
| Nebivolol | Quality of Life | Follow-Up SF-36 (physical) Score | 46.6 units on a scale | Standard Deviation 13.6 |
| Nebivolol | Quality of Life | Follow-Up CSFQ | 53.0 units on a scale | Standard Deviation 5.7 |
| Nebivolol | Quality of Life | Change from Baseline CSFQ | 4.5 units on a scale | Standard Deviation 6.4 |
| Nebivolol | Quality of Life | Follow-Up MAF Score | 22.1 units on a scale | Standard Deviation 12.2 |
| Nebivolol | Quality of Life | Baseline SF-36 (physical) Score | 41.1 units on a scale | Standard Deviation 5.3 |
| Nebivolol | Quality of Life | Change from Baseline MAF | -5.6 units on a scale | Standard Deviation 6.3 |
| Nebivolol | Quality of Life | Change from Baseline SF-36 (physical) | 5.5 units on a scale | Standard Deviation 10.1 |
| Nebivolol | Quality of Life | Follow-Up SF-36 (mental) Score | 48 units on a scale | Standard Deviation 11.7 |
| Nebivolol | Quality of Life | Change from Baseline SF-36 (mental) | 7.4 units on a scale | Standard Deviation 8 |
| Nebivolol | Quality of Life | Baseline IIEF Score | 10.3 units on a scale | Standard Deviation 15.3 |
| Nebivolol | Quality of Life | Change from Baseline IIEF | 6.7 units on a scale | Standard Deviation 9.9 |
| Nebivolol | Quality of Life | Baseline CSFQ | 48.7 units on a scale | Standard Deviation 0.6 |
| Nebivolol | Quality of Life | Follow-Up IIEF Score | 16.3 units on a scale | Standard Deviation 14.6 |
| Metoprolol | Quality of Life | Follow-Up CSFQ | 49 units on a scale | Standard Deviation 0 |
| Metoprolol | Quality of Life | Baseline SF-36 (mental) Score | 40.3 units on a scale | Standard Deviation 11.1 |
| Metoprolol | Quality of Life | Follow-Up SF-36 (mental) Score | 42.7 units on a scale | Standard Deviation 13.3 |
| Metoprolol | Quality of Life | Change from Baseline SF-36 (mental) | 2.4 units on a scale | Standard Deviation 7.1 |
| Metoprolol | Quality of Life | Baseline MAF Score | 31.7 units on a scale | Standard Deviation 8.6 |
| Metoprolol | Quality of Life | Change from Baseline MAF | -13.9 units on a scale | Standard Deviation 9.1 |
| Metoprolol | Quality of Life | Baseline IIEF Score | 15 units on a scale | Standard Deviation 9.8 |
| Metoprolol | Quality of Life | Follow-Up IIEF Score | 14.3 units on a scale | Standard Deviation 12.3 |
| Metoprolol | Quality of Life | Change from Baseline IIEF | -1.3 units on a scale | Standard Deviation 0.6 |
| Metoprolol | Quality of Life | Baseline CSFQ | 49 units on a scale | Standard Deviation 0 |
| Metoprolol | Quality of Life | Change from Baseline CSFQ | 0 units on a scale | Standard Deviation 0 |
| Metoprolol | Quality of Life | Follow-Up SF-36 (physical) Score | 43.6 units on a scale | Standard Deviation 15.1 |
| Metoprolol | Quality of Life | Change from Baseline SF-36 (physical) | -2.3 units on a scale | Standard Deviation 8.4 |
| Metoprolol | Quality of Life | Follow-Up MAF Score | 17.8 units on a scale | Standard Deviation 12.2 |
| Metoprolol | Quality of Life | Baseline SF-36 (physical) Score | 45.9 units on a scale | Standard Deviation 13.3 |
Secondary
Blood Pressure
Evaluate the baseline and follow-up systolic and diastolic blood pressures for all subjects in both groups.
Time frame: 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nebivolol | Blood Pressure | Baseline Diastolic Blood Pressure | 73.2 mmHg | Standard Deviation 8.5 |
| Nebivolol | Blood Pressure | Change from Baseline Diastolic Blood Pressure | 1.6 mmHg | Standard Deviation 4.8 |
| Nebivolol | Blood Pressure | Follow-Up Systolic Blood Pressure | 142.8 mmHg | Standard Deviation 10.7 |
| Nebivolol | Blood Pressure | Change from Baseline Systolic Blood Pressure | 3.6 mmHg | Standard Deviation 8.9 |
| Nebivolol | Blood Pressure | Follow-Up Diastolic Blood Pressure | 76.0 mmHg | Standard Deviation 5.7 |
| Nebivolol | Blood Pressure | Baseline Systolic Blood Pressure | 142.3 mmHg | Standard Deviation 14.6 |
| Metoprolol | Blood Pressure | Change from Baseline Diastolic Blood Pressure | -4.0 mmHg | Standard Deviation 11.2 |
| Metoprolol | Blood Pressure | Baseline Systolic Blood Pressure | 138.8 mmHg | Standard Deviation 14.3 |
| Metoprolol | Blood Pressure | Baseline Diastolic Blood Pressure | 77.0 mmHg | Standard Deviation 9.9 |
| Metoprolol | Blood Pressure | Follow-Up Diastolic Blood Pressure | 73.0 mmHg | Standard Deviation 13.7 |
| Metoprolol | Blood Pressure | Follow-Up Systolic Blood Pressure | 136.0 mmHg | Standard Deviation 13.9 |
| Metoprolol | Blood Pressure | Change from Baseline Systolic Blood Pressure | -2.8 mmHg | Standard Deviation 9.9 |