Hypertension in Hemodialysis Patients (Aim 3)

• Sponsor: Indiana University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00582114
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Enrollment: 200
• Location: 1
• Arms: 2
• Duration (Months): 97
• Patients Per Site Per Month: 2.1

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Hemodialysis; Hypertension; Left Ventricular Hypertrophy	Drug: Lisinopril; Drug: Atenolol	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Hypertension in Hemodialysis Patients
• Study Start Date: Aug 1, 2005
• Actual Primary Completion Date: Sep 1, 2013
• Actual Study Completion Date: Sep 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
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.

Outcome Measures

Primary Outcome Measures

1. The Primary End Point is the Regression of Left Ventricular Hypertrophy (LVH) by Echocardiographic Criteria From Baseline to 1 Year. [Baseline, 6 months, 12 months]

   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

1. Serious Adverse Events and Cardiovascular Events That Led to Trial Termination [1 yr]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Indiana University
• ClinicalTrials.gov Identifier: NCT00582114
• Other Study ID Numbers: 0306-13; R01DK062030; NIH-NIDDK-5RO1-062030
• First Posted: Dec 28, 2007
• Last Update Posted: Jan 18, 2016
• Last Verified: Dec 1, 2015

• Keywords provided by Indiana University: Hemodialysis; Hypertension; Left ventricular hypertrophy
• Additional relevant MeSH terms: Hypertension; Hypertrophy, Left Ventricular; Hypertrophy; Atenolol; Lisinopril

Study Results

Participant Flow

Arm/Group Title	Atenolol	Lisinopril
Arm/Group Description	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.	Lisinopril: Patients will be randomized into two groups, one that is beta blocker based, the other 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.
Period Title: Overall Study
STARTED	100	100
COMPLETED	58	46
NOT COMPLETED	42	54

Baseline Characteristics

Arm/Group Title	Atenolol	Lisinopril	Total
Arm/Group Description	Atenolol: Patients will be randomized into two groups, one that is beta blocker based, the other 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.	Lisinopril: Patients will be randomized into two groups, one that is beta blocker based, the other 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.	Total of all reporting groups
Overall Participants	100	100	200
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.5 (11.7)	53.1 (13.5)	52.7 (12.6)
Sex: Female, Male (Count of Participants)
Female	27 27%	42 42%	69 34.5%
Male	73 73%	58 58%	131 65.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 1%	0 0%	1 0.5%
Not Hispanic or Latino	99 99%	100 100%	199 99.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (participants) [Number]
Blacks	86 86%	86 86%	172 86%
Non-blacks	14 14%	14 14%	28 14%
Region of Enrollment (participants) [Number]
United States	100 100%	100 100%	200 100%
Etiology of chronic kidney disease (participants) [Number]
Diabetes mellitus	29 29%	27 27%	56 28%
Hypertension	54 54%	46 46%	100 50%
Glomerulonephritis	4 4%	5 5%	9 4.5%
Polycystic kidney disease	0 0%	1 1%	1 0.5%
Other etiologies	13 13%	21 21%	34 17%
Dialysis vintage (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	4.2 (4.4)	3.9 (4.2)	4.1 (4.3)
Anuric (participants) [Number]
Number [participants]	68 68%	66 66%	134 67%
Education (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	12 (2)	12 (2)	12 (2)
Comorbid conditions (participants) [Number]
Diabetes mellitus	43 43%	43 43%	86 43%
Hospitalized heart failure	25 25%	37 37%	62 31%
Coronary artery disease	22 22%	31 31%	53 26.5%
Coronary revascularization	4 4%	15 15%	19 9.5%
Cerebrovascular disease	13 13%	20 20%	33 16.5%
Peripheral vascular disease	10 10%	11 11%	21 10.5%
Marital status (participants) [Number]
Single	53 53%	56 56%	109 54.5%
Married	23 23%	19 19%	42 21%
Divorced/separated	18 18%	15 15%	33 16.5%
Widowed	6 6%	10 10%	16 8%
Employed (participants) [Number]
Working	11 11%	7 7%	18 9%
Not working	67 67%	70 70%	137 68.5%
Retired	22 22%	23 23%	45 22.5%
Income (participants) [Number]
< $25,000	84 84%	80 80%	164 82%
>= $25,000	10 10%	7 7%	17 8.5%
Refused	6 6%	13 13%	19 9.5%
Smoking (participants) [Number]
Current smoker	43 43%	43 43%	86 43%
Non-smoker	57 57%	57 57%	114 57%
Alcohol (participants) [Number]
Drinks alcohol	27 27%	19 19%	46 23%
Does not drink alcohol	73 73%	81 81%	154 77%
Height (inches) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [inches]	68.3 (4.1)	67.6 (3.7)	67.9 (3.9)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	85.1 (21.7)	80.9 (24.3)	83 (23.1)
Body mass index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	28.4 (7)	27.5 (8.3)	27.9 (7.7)
Access type (participants) [Number]
Fistula	59 59%	59 59%	118 59%
Graft	16 16%	14 14%	30 15%
Catheter	25 25%	27 27%	52 26%
Blood flow rate (mL/min) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mL/min]	394.3 (30.9)	392.4 (36.4)	393.4 (33.7)
Dialysate flow rate (mL/min) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mL/min]	779.6 (61.9)	761.3 (82)	770.4 (73)
Dialysis duration (minutes) [Mean (Standard Deviation) ]
Prescribed dialysis duration	239.4 (19)	239.4 (25.9)	239.4 (22.7)
Delivered dialysis duration	224.1 (34.7)	219.8 (33.7)	222 (34.2)
Urea reduction ratio (%) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [%]	74 (8)	76 (8)	75 (8)
Albumin (g/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [g/dL]	3.6 (0.5)	3.6 (0.5)	3.6 (0.5)
Hemoglobin (g/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [g/dL]	11.3 (1.2)	11.3 (1.4)	11.3 (1.3)
Creatinine (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	10.3 (3.5)	10 (3.6)	10.1 (3.6)

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population 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. The analysis was performed by intention to treat, if the patient received at least one dose of the randomized drug regardless of the availability of a post-baseline echocardiogram.

Arm/Group Title	Atenolol	Lisinopril
Arm/Group Description	Atenolol: Patients will be randomized into two groups, one that is beta blocker based, the other 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.	Lisinopril: Patients will be randomized into two groups, one that is beta blocker based, the other 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.
Measure Participants	100	100
LVMI Change from baseline, 6 months	-8.4 (5.1)	-3.4 (5.5)
LVMI Change from baseline, 12 months	-21.5 (5.7)	-15.1 (6.2)

2. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Atenolol	Lisinopril
Arm/Group Description	Atenolol: Patients will be randomized into two groups, one that is beta blocker based, the other 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.	Lisinopril: Patients will be randomized into two groups, one that is beta blocker based, the other 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.
Measure Participants	100	100
Incidence rate, cardiovasular events	24.6	58
Incidence rate, combined MI, stroke, CHF, CV death	13.5	31
Incidence rate, congest heart failure	6.2	20.2
Incidence rate, all-cause hospitalizations	89.9	144.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atenolol, Lisinopril
	Comments	Cardiovascular events were counted by subject and included the following: myocardial infarction, stroke, hospitalization for congestive heart failure, hospitalized angina, arrhythmias, cardiac arrest, coronary revascularization and heart valve replacement. The duration of participation in the study per subject, which according to the trial design could be up to 12 months, was determined. Incidence rate ratio (IRR) by treatment was then determined along with the 95%confidence intervals (95% CIs).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	2.36
	Confidence Interval	(2-Sided) 95%; 1.36 to 4.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Atenolol, Lisinopril
	Comments	As a post hoc analysis, we determined the narrower definition of cardiovascular events per group that included myocardial infarction, stroke, congestive heart failure or cardiovascular death. The duration of participation in the study per subject, which according to the trial design could be up to 12 months, was determined. Incidence rate ratio (IRR) by treatment was then determined along with the 95%confidence intervals (95% CIs).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.02
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	2.29
	Confidence Interval	(2-Sided) 95%; 1.07 to 5.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Atenolol, Lisinopril
	Comments	Hospitalization for congestive heart failure between groups was analyzed. The duration of participation in the study per subject, which according to the trial design could be up to 12 months, was determined. Incidence rate ratio (IRR) by treatment was then determined along with the 95%confidence intervals.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.02
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	3.13
	Confidence Interval	(2-Sided) 95%; 1.08 to 10.99
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Atenolol, Lisinopril
	Comments	All-cause hospitalizations between groups were analyzed. The duration of participation in the study per subject, which according to the trial design could be up to 12 months, was determined. Incidence rate ratio (IRR) by treatment was then determined along with the 95%confidence intervals.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.61
	Confidence Interval	(2-Sided) 95%; 1.18 to 2.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Atenolol		Lisinopril
Arm/Group Description	Atenolol: Patients will be randomized into two groups, one that is beta blocker based, the other 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.		Lisinopril: Patients will be randomized into two groups, one that is beta blocker based, the other 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.
All Cause Mortality
	Atenolol		Lisinopril
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Atenolol		Lisinopril
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	58/100 (58%)		70/100 (70%)
Cardiac disorders
Angina	0/100 (0%)	0	2/100 (2%)	2
Arrhythmia	2/100 (2%)	2	3/100 (3%)	5
Cardiac arrest	0/100 (0%)	0	2/100 (2%)	2
Congestive heart failure	5/100 (5%)	5	10/100 (10%)	15
Myocardial infarction	2/100 (2%)	2	3/100 (3%)	3
Peripheral vascular disease	1/100 (1%)	1	5/100 (5%)	6
Revascularization	3/100 (3%)	4	4/100 (4%)	4
Stroke	2/100 (2%)	2	2/100 (2%)	2
Valve replacement surgery	1/100 (1%)	1	1/100 (1%)	1
Cardiovascular death	2/100 (2%)	2	3/100 (3%)	3
Endocrine disorders
Parathyroidectomy	3/100 (3%)	3	1/100 (1%)	1
Hyperglycemia	1/100 (1%)	2	3/100 (3%)	3
Hypoglycemia	2/100 (2%)	3	4/100 (4%)	4
Gastrointestinal disorders
Bowel-related	3/100 (3%)	3	5/100 (5%)	5
Gastrointestinal bleed	2/100 (2%)	4	5/100 (5%)	7
General disorders
Noncardiovascular death	2/100 (2%)	2	1/100 (1%)	1
Falls	6/100 (6%)	6	3/100 (3%)	3
Hypertensive crisis	3/100 (3%)	3	10/100 (10%)	11
Hypotension with hospitalization	6/100 (6%)	8	5/100 (5%)	5
Miscellaneous	12/100 (12%)	14	18/100 (18%)	24
Hepatobiliary disorders
Biliary-related	1/100 (1%)	1	2/100 (2%)	2
Infections and infestations
Infections	24/100 (24%)	30	20/100 (20%)	29
Musculoskeletal and connective tissue disorders
Fractures	7/100 (7%)	7	1/100 (1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer-related complications	2/100 (2%)	4	2/100 (2%)	3
Nervous system disorders
Central nervous system	3/100 (3%)	3	3/100 (3%)	5
Renal and urinary disorders
Access-related	17/100 (17%)	24	19/100 (19%)	30
Hyperkalemia	3/100 (3%)	3	10/100 (10%)	10
Other (Not Including Serious) Adverse Events
	Atenolol		Lisinopril
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	44/100 (44%)		29/100 (29%)
Gastrointestinal disorders
Gastrointestinal disorders	5/100 (5%)	6	6/100 (6%)	6
General disorders
Fatigue	20/100 (20%)	25	6/100 (6%)	12
bradycardia	2/100 (2%)	3	1/100 (1%)	1
Intradialytic hypotension	6/100 (6%)	7	4/100 (4%)	4
tachycardia	1/100 (1%)	1	1/100 (1%)	1
Dialysis access-related events	0/100 (0%)	0	1/100 (1%)	1
Hypertension	1/100 (1%)	1	2/100 (2%)	3
Other	19/100 (19%)	23	17/100 (17%)	29
Infections and infestations
Upper respiratory infection	1/100 (1%)	1	2/100 (2%)	4
Skin and subcutaneous tissue disorders
Rash	1/100 (1%)	2	2/100 (2%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.