Predischarge Initiation of Ivabradine in the Management of Heart Failure (PRIME-HF)

• Sponsor: Duke University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02827500
• Collaborator: Amgen (Industry)
• Enrollment: 104
• Locations: 20
• Arms: 2
• Duration (Months): 27.5
• Patients Per Site: 5.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The PRIME-HF study is a multi-center, patient-level, randomized, open-label study of approximately 450 patients with reduced (left ventricular ejection fraction) LVEF of ≤ 35% and heart-rate ≥70 beats per minute (bpm) who are being discharged from the hospital following stabilization from acute heart failure (HF)(primary or secondary) and will be randomized to a treatment strategy of predischarge initiation of ivabradine or usual care.

All participants should have a follow-up visit within 7-14 days of hospital discharge. Heart rate and systolic blood pressure will be assessed at this clinical visit. For participants randomized to predischarge initiation of ivabradine and on ivabradine 5mg BID, the heart rate may be used to adjust the dose the dose to 2.5mg BID or 7.5mg BID. For participants randomized to usual care, ivabradine may be initiated at the provider's discretion. All participants will have a second follow-up study visit 6 weeks (42 +/- 14 days) post-discharge. Heart rate, systolic blood pressure and quality of life (KCCQ and PGA) will be assessed. For participants already taking ivabradine in either treatment group, the heart rate may again be used to adjust the dose of ivabradine. For participants not yet receiving ivabradine, it may be initiated at the provider's discretion. All participants will receive a 90 (+/-7) day post-discharge phone call by site to assess for event status and tolerability of ivabradine. All participants will have a final study visit at 180 (+/-14) days post-discharge. Heart rate, systolic blood pressure and quality of life (Kansas City Cardiomyopathy Questionnaire and Patient Global Assessment) will be assessed. The attending physician may initiate ivabradine per usual care clinical practice.

The primary hypothesis of the PRIME-HF study is that, compared with usual care, a treatment strategy of initiation of ivabradine prior to discharge for a hospitalization with acute HF will be associated with a greater proportion of participants using ivabradine at 180 days. Secondary objectives are to assess the impact of predischarge initiation of ivabradine on:Heart Rate (Change in heart rate from baseline to 180 days and Median heart rate at 180 days) and Patient-Centered Outcomes (Kansas City Cardiomyopathy Questionnaire (KCCQ) and Patient Global Assessment (PGA)). Tertiary objectives will be to explore the impact of predischarge initiation of ivabradine on other assessments of evidence-based implementation of ivabradine and beta-blockers at 180 days. Evaluations will incorporate data based on whether or not indication status was retained and whether or not an ivabradine prescription was provided. Tolerability of ivabradine and adverse events during study follow-up.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure	Drug: ivabradine; Other: Usual Care	Phase 4

Detailed Description

• Purpose of the study The primary hypothesis of the PRIME-HF study is that, compared with usual care, a treatment strategy of initiation of ivabradine prior to discharge for a hospitalization with acute HF (primary or secondary) will be associated with a greater proportion of participants using ivabradine at 180 days. Secondary objectives are to assess the impact of predischarge initiation of ivabradine on:Heart Rate (Change in heart rate from baseline to 180 days and Median heart rate at 180 days) and Patient-Centered Outcomes (Kansas City Cardiomyopathy Questionnaire (KCCQ) and Patient Global Assessment (PGA)). Tertiary objectives will be to explore the impact of predischarge initiation of ivabradine on other assessments of evidence-based implementation of ivabradine and beta-blockers at 180 days. Evaluations will incorporate data based on whether or not indication status was retained and whether or not an ivabradine prescription was provided. Tolerability of ivabradine and adverse events during study follow-up will be assessed. Barriers to acquisition of ivabradine will be explored.

• Background & significance Heart failure is a major public health issue. More than 5 million Americans have HF and the prevalence is expected to increase as the population ages and survival from coronary, hypertensive, and valvular heart disease improves. Data from randomized clinical trials have established the efficacy of a number of medical and device therapies for patients with chronic Heart failure with reduced ejection fraction (HFrEF), but patient outcomes remain poor, especially after a hospitalization for heart failure. The 1-year mortality rate after a HF hospitalization is 20-30%, and this number has been relatively unchanged over the past decade. These data suggest that there is an unmet need for novel treatment strategies and supports the assessment of new approaches in the post-acute HF setting.

There is also wide variation in the implementation of clinical trial evidence into routine practice. Previous data highlight a multi-year gap between the generation of new evidence through clinical trials and the adoption of the data into routine clinical practice. This gap in care translates into many unnecessary deaths and hospitalizations each year for patients with HFrEF. While there are multiple reasons for this quality gap, clinical inertia has most often been noted as a major barrier. Ivabradine have been approved for use in Europe for several years for patients with symptomatic chronic HFrEF (LVEF <35%) and a heart rate >75 bpm on guideline-directed medical therapy (or intolerance/contra-indication to beta-blocker use). Ivabradine was recently approved for use in the United States. However, no US data exist regarding the potential adoption of ivabradine into routine clinical care.

Since ivabradine is a newly approved drug, this study also serves as a strategy trial to challenge study sites to explore drug acquisition for a drug that has been proven efficacious to the heart failure population and has been added to 2016 ACC/AHA/HFSA guidelines, however, has not been adopted rapidly into clinical practice. Ivabradine is not being provided for this study. Data are being captured to assess the number of subjects who were able to obtain ivabradine pre and post discharge as well as the barriers to acquisition.

Previous data for patients with HFrEF suggest that the hospital setting may provide a unique opportunity for patients to initiate guideline-directed medical therapy. In the Initiation Management Predischarge: Process for Assessment of Carvedilol Therapy in HF (IMPACT-HF) study, patients with an LVEF<40% hospitalized for HF that were started on carvedilol prior to hospital discharge were more likely to be on a beta-blocker at 60 days post-randomization compared to those receiving usual care. These improvements in care were achieved without increasing side effects or index hospitalization length of stay. Similar to beta-blockers and other medical therapies for HF, ivabradine was initially studied in patients with chronic HF. The initiation of ivabradine specifically in patients following stabilization for acute HF has not been evaluated.

• Design & procedures The PRIME-HF study is a multi-center, patient-level, randomized, open-label study of approximately 450 patients with reduced LVEF of ≤35% and heart-rate ≥70 bpm who are being discharged from the hospital following stabilization from acute HF and will be randomized to a treatment strategy of predischarge initiation of ivabradine or usual care.

All participants should have a follow-up visit within 7-14 days of hospital discharge. Heart rate and systolic blood pressure will be assessed at this clinical visit. For participants randomized to predischarge initiation of ivabradine and on ivabradine 5mg BID, the heart rate may be used to adjust the dose the dose to 2.5mg BID or 7.5mg BID. For participants randomized to usual care, ivabradine may be initiated at the provider's discretion. All participants will have a second follow-up study visit 6 weeks (42 +/- 14 days) post-discharge. Heart rate, systolic blood pressure and quality of life (KCCQ and PGA) will be assessed. For participants already taking ivabradine in either treatment group, the heart rate may again be used to adjust the dose of ivabradine. For participants not yet receiving ivabradine, it may be initiated at the provider's discretion. All participants will receive a 90 (+/-7) day post-discharge phone call by site to assess for event status and tolerability of ivabradine. All participants will have a final study visit at 180 (+/-14) days post-discharge. Heart rate, systolic blood pressure and quality of life (KCCQ and PGA) will be assessed. The attending physician may initiate ivabradine per usual care clinical practice.

Study Design

• Study Type: Interventional
• Actual Enrollment: 104 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Predischarge Initiation of Ivabradine in the Management of Heart Failure (PRIME-HF)
• Study Start Date: Jul 1, 2016
• Actual Primary Completion Date: Oct 15, 2018
• Actual Study Completion Date: Oct 15, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: ivabradine Active Comparator: ivabradine	Drug: ivabradine; Active Comparator: ivabradine; Other Names: Corlanor
Placebo Comparator: usual care Placebo Comparator: usual care	Other: Usual Care; Placebo Comparator: usual care

Outcome Measures

Primary Outcome Measures

1. Number of Participants Taking Ivabradine at 180 Days [180 days]

Secondary Outcome Measures

1. Change in Heart Rate [baseline,180 days]

   Change from baseline is calculated as 180 days - baseline results. Heart rate results are obtained from vital sign assessment when available otherwise results from ECG assessment are used.

2. Heart Rate at 180 Days [180 days]

   Heart rate results are obtained from vital sign assessment when available otherwise results from ECG assessment are used from day 180.

3. Number of Patients With Heart Rate <70 Bpm at 180 Days [180 days]

4. Changes in Symptoms and Quality of Life as Measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score [baseline, 180 days]

   Change from baseline is calculated as 180 day - baseline results. Scores range 0-100, where a higher score indicates a better outcome.

5. Changes in Symptoms and Quality of Life as Measured by Patient Global Assessment (PGA) [baseline, 180 days]

   Change from baseline is calculated as 180 day - baseline results. Scores range 0-100, where a higher score indicates a worse outcome.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Hospitalized with acute HF (primary or secondary diagnosis) based on clinician assessment

2. A prior clinical diagnosis of HF (i.e., not a new diagnosis of heart failure during the current hospitalization)

3. Most recent LVEF ≤ 35% and within 6 months of randomization or LVEF ≤ 25% within 12 months of randomization

4. On optimal guideline-directed medical therapy for HFrEF (or previously deemed intolerant) as determined by the clinician including ACE-inhibitors or angiotensin receptor antagonists or neprilysin inhibition, aldosterone receptor antagonists, and maximally-tolerated doses of beta-blockers at the time of current evaluation (which may differ from long-term targets)

• Maximally-tolerated doses of beta-blockers will be defined by the treating physician when considering aspects such as current dose relative to the target dose used in clinical trials, patient heart rate and blood pressure, and patient symptoms

• Patients with intolerance or contraindication to beta-blocker use are eligible for enrollment (details will be documented in the case report form)

1. Age >18 years

2. Willingness to provide informed consent from the subject (or their guardian or legally authorized representative [LAR])

3. On the day of planned randomization, all participants:

• Must be in sinus rhythm with a resting heart rate >70 bpm as measured on ECG or 10-second rhythm strip

• Must have a blood pressure of >90/50 mm Hg

Exclusion Criteria:

1. Documented plan for uptitration of beta-blocker in the following 4 weeks

2. Permanent atrial fibrillation or atrial flutter

3. Patients with recent atrial fibrillation or flutter defined by either precipitating the current HF hospitalization or occurring during the current HF hospitalization

4. History of untreated sick sinus syndrome, sinoatrial block, or second and third degree atrio-ventricular block

5. Pacemaker with atrial or ventricular pacing (except biventricular pacing) >40% of the time

6. Family history or congenital long QT syndrome

7. Recent myocardial infarction (<2 months prior to screening) [troponin elevation secondary to acute HF as determined by the clinician is not an exclusion]

8. Acute or chronic severe liver disease as evidenced by any of the following: encephalopathy, variceal bleeding, INR > 1.7 in the absence of anticoagulation treatment

9. Creatinine clearance <15 mL/min within 48 hours of screening that was not due to acute kidney injury that resolved

10. Planned mechanical circulatory support within 180 days

11. Pregnant or breastfeeding women. Women with child-bearing potential should use effective contraception.

12. Medical conditions likely to lead to poor non-cardiac survival at 180 days (e.g., cancer)

13. Inability to comply with planned study procedures

14. If the following medications are needed at inclusion or during the study:

• Non-dihydropyridine calcium channel blockers (e.g., diltiazem and verapamil)

• Class I anti-arrhythmics (e.g., quinidine, procainamide, lidocaine, phenytoin)

• Strong inhibitors of cytochrome P450 3A4 (CYP3A4), including some macrolide antibiotics (e.g., clarithromycin, erythromycin), cyclosporine, antiretroviral drugs (e.g., ritonavir, nelfinavir), and systemic azole antifungal agents (e.g., ketoconazole, itraconazole), and nefazodone

• Inducers of cytochrome P450 3A4 (CYP3A4) including St. John's wort, rifampicin, barbiturates, and phenytoin.

• Treatments known to be associated with significant prolongation of the QT interval, including sotalol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado at Denver and Health Sciences Center	Aurora	Colorado	United States	80045
2	Holy Cross Hospital	Fort Lauderdale	Florida	United States	33308
3	Athens Regional Medical Center	Athens	Georgia	United States	30606
4	University Hospital	Augusta	Georgia	United States	30901
5	Tanner Medical Center	Carrollton	Georgia	United States	30117
6	Midwest Cardiovascular Research	Elkhart	Indiana	United States	46514
7	Saint Vincent Medical Group, Inc.	Indianapolis	Indiana	United States	46260
8	Great Lakes Heart Center of Alpena	Alpena	Michigan	United States	49707
9	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
10	Montefiore Medical Center	Bronx	New York	United States	10467
11	New York Methodist Hospital	Brooklyn	New York	United States	11215
12	Mount Sinai Medical Center	New York	New York	United States	10029-6574
13	Duke University	Durham	North Carolina	United States	27705
14	University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44106
15	Ohio State University- Davis Heart and Lung Research Institute	Columbus	Ohio	United States	43210
16	Stern Cardiovascular Foundation	Germantown	Tennessee	United States	38138
17	Baylor University Medical Center	Dallas	Texas	United States	75226
18	William Beaumont Army Medical Center	El Paso	Texas	United States	79912
19	Sentara Norfolk General Hospital	Norfolk	Virginia	United States	23507
20	Gundersen Lutheran Medical Center	La Crosse	Wisconsin	United States	54601

Sponsors and Collaborators

• Duke University
• Amgen

Investigators

• Principal Investigator: Robert Mentz, MD, Duke Clinical Research Institute

Study Documents (Full-Text)

• Study Protocol - Jul 19, 2017
• Statistical Analysis Plan - Jan 11, 2019

More Information

Publications

None provided.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT02827500
• Other Study ID Numbers: Pro00071309
• First Posted: Jul 11, 2016
• Last Update Posted: Oct 1, 2019
• Last Verified: Sep 1, 2019

• Additional relevant MeSH terms: Heart Failure

Study Results

Participant Flow

Recruitment Details	Subjects hospitalized with acute heart failure were randomized prior to discharge from September 2016- April 2018.

Arm/Group Title	Usual Care	Pre-discharge Ivabradine
Arm/Group Description	Placebo Comparator: usual care Usual Care: Placebo Comparator: usual care	Active Comparator: ivabradine ivabradine: Active Comparator: ivabradine
Period Title: Overall Study
STARTED	52	52
COMPLETED	33	45
NOT COMPLETED	19	7

Baseline Characteristics

Arm/Group Title	Usual Care	Pre-discharge Ivabradine	Total
Arm/Group Description	Placebo Comparator: usual care Usual Care: Placebo Comparator: usual care	Active Comparator: ivabradine ivabradine: Active Comparator: ivabradine	Total of all reporting groups
Overall Participants	52	52	104
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.5 (12)	56.5 (14.8)	57.5 (13.5)
Sex: Female, Male (Count of Participants)
Female	23 44.2%	14 26.9%	37 35.6%
Male	29 55.8%	38 73.1%	67 64.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	6 11.5%	6 11.5%	12 11.5%
Not Hispanic or Latino	46 88.5%	41 78.8%	87 83.7%
Unknown or Not Reported	0 0%	5 9.6%	5 4.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 1.9%	1 1%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	34 65.4%	33 63.5%	67 64.4%
White	17 32.7%	17 32.7%	34 32.7%
More than one race	0 0%	1 1.9%	1 1%
Unknown or Not Reported	1 1.9%	0 0%	1 1%
Region of Enrollment (Count of Participants)
United States	52 100%	52 100%	104 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Taking Ivabradine at 180 Days
Time Frame	180 days

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	Usual Care	Pre-discharge Ivabradine
Arm/Group Description	Placebo Comparator: usual care Usual Care: Placebo Comparator: usual care	Active Comparator: ivabradine ivabradine: Active Comparator: ivabradine
Measure Participants	52	52
Count of Participants [Participants]	6 11.5%	21 40.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care, Pre-discharge Ivabradine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio, log
	Estimated Value	5.19
	Confidence Interval	(2-Sided) 95%; 1.88 to 14.33
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change in Heart Rate
Description	Change from baseline is calculated as 180 days - baseline results. Heart rate results are obtained from vital sign assessment when available otherwise results from ECG assessment are used.
Time Frame	baseline,180 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Usual Care	Pre-discharge Ivabradine
Arm/Group Description	Placebo Comparator: usual care Usual Care: Placebo Comparator: usual care	Active Comparator: ivabradine ivabradine: Active Comparator: ivabradine
Measure Participants	52	52
Mean (Standard Deviation) [beats per minute]	-10.2 (20.6)	0.9 (16.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care, Pre-discharge Ivabradine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.011
	Comments
	Method	Regression, Linear
	Comments

3. Secondary Outcome

Title	Heart Rate at 180 Days
Description	Heart rate results are obtained from vital sign assessment when available otherwise results from ECG assessment are used from day 180.
Time Frame	180 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Usual Care	Pre-discharge Ivabradine
Arm/Group Description	Placebo Comparator: usual care Usual Care: Placebo Comparator: usual care	Active Comparator: ivabradine ivabradine: Active Comparator: ivabradine
Measure Participants	52	52
Mean (Standard Deviation) [beats per minute]	85.4 (16.7)	77.2 (16.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care, Pre-discharge Ivabradine
	Comments	The null hypothesis tested was that there is no difference in change in heart rate between the treatment arms.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.011
	Comments
	Method	Regression, Linear
	Comments

4. Secondary Outcome

Title	Number of Patients With Heart Rate <70 Bpm at 180 Days
Time Frame	180 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Usual Care	Pre-discharge Ivabradine
Arm/Group Description	Placebo Comparator: usual care Usual Care: Placebo Comparator: usual care	Active Comparator: ivabradine ivabradine: Active Comparator: ivabradine
Measure Participants	52	52
Count of Participants [Participants]	11 21.2%	20 38.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care, Pre-discharge Ivabradine
	Comments	The null hypothesis tested was that there is no difference between the treatment arms in the proportion of patients with heart rate < 70 BPM.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.054
	Comments	The apriori threshold for statistical significance is alpha=0.05.
	Method	Chi-squared, Corrected
	Comments	The p-value is obtained using the F-test (combination of Chi-Squared tests) due to multiple imputation.

5. Secondary Outcome

Title	Changes in Symptoms and Quality of Life as Measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score
Description	Change from baseline is calculated as 180 day - baseline results. Scores range 0-100, where a higher score indicates a better outcome.
Time Frame	baseline, 180 days

Outcome Measure Data

Analysis Population Description

Participants who completed the KCCQ at both timepoints.

Arm/Group Title	Usual Care	Pre-discharge Ivabradine
Arm/Group Description	Placebo Comparator: usual care Usual Care: Placebo Comparator: usual care	Active Comparator: ivabradine ivabradine: Active Comparator: ivabradine
Measure Participants	29	38
Mean (Standard Deviation) [score on a scale]	25.1 (23.9)	23.2 (32)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care, Pre-discharge Ivabradine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.717
	Comments
	Method	Regression, Linear
	Comments

6. Secondary Outcome

Title	Changes in Symptoms and Quality of Life as Measured by Patient Global Assessment (PGA)
Description	Change from baseline is calculated as 180 day - baseline results. Scores range 0-100, where a higher score indicates a worse outcome.
Time Frame	baseline, 180 days

Outcome Measure Data

Analysis Population Description

Participants who completed the PGA at both timepoints.

Arm/Group Title	Usual Care	Pre-discharge Ivabradine
Arm/Group Description	Placebo Comparator: usual care Usual Care: Placebo Comparator: usual care	Active Comparator: ivabradine ivabradine: Active Comparator: ivabradine
Measure Participants	29	38
Mean (Standard Deviation) [score on a scale]	13 (26)	14.8 (29.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care, Pre-discharge Ivabradine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.784
	Comments
	Method	Regression, Linear
	Comments

Adverse Events

Time Frame	Events through day 194 (6 month +/- 2 week window)
Adverse Event Reporting Description	Only events of interest, serious and unexpected events, and events related to ivabradine use in the opinion of the site investigators were collected.
Arm/Group Title	Usual Care		Pre-discharge Ivabradine
Arm/Group Description	Placebo Comparator: usual care Usual Care: Placebo Comparator: usual care		Active Comparator: ivabradine ivabradine: Active Comparator: ivabradine
All Cause Mortality
	Usual Care		Pre-discharge Ivabradine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/52 (13.5%)		3/52 (5.8%)
Serious Adverse Events
	Usual Care		Pre-discharge Ivabradine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/52 (3.8%)		3/52 (5.8%)
Cardiac disorders
Cardiac failure	0/52 (0%)	0	1/52 (1.9%)	1
Ventricular Fibrillation	1/52 (1.9%)	1	0/52 (0%)	0
Bradycardia	1/52 (1.9%)	1	0/52 (0%)	0
Nervous system disorders
Toxic Encephalopathy	0/52 (0%)	0	1/52 (1.9%)	1
Renal and urinary disorders
Chronic Kidney Disease	0/52 (0%)	0	1/52 (1.9%)	1
Other (Not Including Serious) Adverse Events
	Usual Care		Pre-discharge Ivabradine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/52 (19.2%)		1/52 (1.9%)
Cardiac disorders
Bradycardia	1/52 (1.9%)	1	1/52 (1.9%)	1
Gastrointestinal disorders
Nausea	1/52 (1.9%)	1	0/52 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	1/52 (1.9%)	1	0/52 (0%)	0
Nervous system disorders
Dizziness	1/52 (1.9%)	1	0/52 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	1/52 (1.9%)	1	0/52 (0%)	0
Skin and subcutaneous tissue disorders
Hyperhydrosis	1/52 (1.9%)	1	0/52 (0%)	0
Vascular disorders
Hypotension	4/52 (7.7%)	4	0/52 (0%)	0

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.