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

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.
 
ClinicalTrials.gov Identifier: NCT02827500
Recruitment Status : Completed
First Posted : July 11, 2016
Results First Posted : October 1, 2019
Last Update Posted : October 1, 2019
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
Duke University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Heart Failure
Interventions Drug: ivabradine
Other: Usual Care
Enrollment 104
Recruitment Details Subjects hospitalized with acute heart failure were randomized prior to discharge from September 2016- April 2018.
Pre-assignment Details  
Arm/Group Title Usual Care Pre-discharge Ivabradine
Hide 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
Reason Not Completed
Death             7             3
Lost to Follow-up             1             1
Withdrawal by Subject             3             1
Missing primary endpoint data             3             1
Other             5             1
Arm/Group Title Usual Care Pre-discharge Ivabradine Total
Hide 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 Number of Baseline Participants 52 52 104
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 52 participants 52 participants 104 participants
58.5  (12) 56.5  (14.8) 57.5  (13.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 52 participants 52 participants 104 participants
Female
23
  44.2%
14
  26.9%
37
  35.6%
Male
29
  55.8%
38
  73.1%
67
  64.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 52 participants 52 participants 104 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
   0.0%
5
   9.6%
5
   4.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 52 participants 52 participants 104 participants
American Indian or Alaska Native
0
   0.0%
1
   1.9%
1
   1.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
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
   0.0%
1
   1.9%
1
   1.0%
Unknown or Not Reported
1
   1.9%
0
   0.0%
1
   1.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 52 participants 52 participants 104 participants
52
 100.0%
52
 100.0%
104
 100.0%
1.Primary Outcome
Title Number of Participants Taking Ivabradine at 180 Days
Hide Description [Not Specified]
Time Frame 180 days
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population
Arm/Group Title Usual Care Pre-discharge Ivabradine
Hide Arm/Group Description:

Placebo Comparator: usual care

Usual Care: Placebo Comparator: usual care

Active Comparator: ivabradine

ivabradine: Active Comparator: ivabradine

Overall Number of Participants Analyzed 52 52
Measure Type: Count of Participants
Unit of Measure: Participants
6
  11.5%
21
  40.4%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, Pre-discharge Ivabradine
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 5.19
Confidence Interval (2-Sided) 95%
1.88 to 14.33
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change in Heart Rate
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Usual Care Pre-discharge Ivabradine
Hide Arm/Group Description:

Placebo Comparator: usual care

Usual Care: Placebo Comparator: usual care

Active Comparator: ivabradine

ivabradine: Active Comparator: ivabradine

Overall Number of Participants Analyzed 52 52
Mean (Standard Deviation)
Unit of Measure: beats per minute
-10.2  (20.6) 0.9  (16.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, Pre-discharge Ivabradine
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.011
Comments [Not Specified]
Method Regression, Linear
Comments [Not Specified]
3.Secondary Outcome
Title Heart Rate at 180 Days
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Usual Care Pre-discharge Ivabradine
Hide Arm/Group Description:

Placebo Comparator: usual care

Usual Care: Placebo Comparator: usual care

Active Comparator: ivabradine

ivabradine: Active Comparator: ivabradine

Overall Number of Participants Analyzed 52 52
Mean (Standard Deviation)
Unit of Measure: beats per minute
85.4  (16.7) 77.2  (16.9)
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.011
Comments [Not Specified]
Method Regression, Linear
Comments [Not Specified]
4.Secondary Outcome
Title Number of Patients With Heart Rate <70 Bpm at 180 Days
Hide Description [Not Specified]
Time Frame 180 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Usual Care Pre-discharge Ivabradine
Hide Arm/Group Description:

Placebo Comparator: usual care

Usual Care: Placebo Comparator: usual care

Active Comparator: ivabradine

ivabradine: Active Comparator: ivabradine

Overall Number of Participants Analyzed 52 52
Measure Type: Count of Participants
Unit of Measure: Participants
11
  21.2%
20
  38.5%
Hide 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 [Not Specified]
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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who completed the KCCQ at both timepoints.
Arm/Group Title Usual Care Pre-discharge Ivabradine
Hide Arm/Group Description:

Placebo Comparator: usual care

Usual Care: Placebo Comparator: usual care

Active Comparator: ivabradine

ivabradine: Active Comparator: ivabradine

Overall Number of Participants Analyzed 29 38
Mean (Standard Deviation)
Unit of Measure: score on a scale
25.1  (23.9) 23.2  (32)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, Pre-discharge Ivabradine
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.717
Comments [Not Specified]
Method Regression, Linear
Comments [Not Specified]
6.Secondary Outcome
Title Changes in Symptoms and Quality of Life as Measured by Patient Global Assessment (PGA)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who completed the PGA at both timepoints.
Arm/Group Title Usual Care Pre-discharge Ivabradine
Hide Arm/Group Description:

Placebo Comparator: usual care

Usual Care: Placebo Comparator: usual care

Active Comparator: ivabradine

ivabradine: Active Comparator: ivabradine

Overall Number of Participants Analyzed 29 38
Mean (Standard Deviation)
Unit of Measure: score on a scale
13  (26) 14.8  (29.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, Pre-discharge Ivabradine
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.784
Comments [Not Specified]
Method Regression, Linear
Comments [Not Specified]
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
Hide 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 (%) Affected / at Risk (%)
Total   7/52 (13.46%)      3/52 (5.77%)    
Hide Serious Adverse Events
Usual Care Pre-discharge Ivabradine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/52 (3.85%)      3/52 (5.77%)    
Cardiac disorders     
Cardiac failure  1  0/52 (0.00%)  0 1/52 (1.92%)  1
Ventricular Fibrillation  1  1/52 (1.92%)  1 0/52 (0.00%)  0
Bradycardia  1  1/52 (1.92%)  1 0/52 (0.00%)  0
Nervous system disorders     
Toxic Encephalopathy  1  0/52 (0.00%)  0 1/52 (1.92%)  1
Renal and urinary disorders     
Chronic Kidney Disease  1  0/52 (0.00%)  0 1/52 (1.92%)  1
1
Term from vocabulary, MedDRA (21.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Usual Care Pre-discharge Ivabradine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   10/52 (19.23%)      1/52 (1.92%)    
Cardiac disorders     
Bradycardia  1  1/52 (1.92%)  1 1/52 (1.92%)  1
Gastrointestinal disorders     
Nausea  1  1/52 (1.92%)  1 0/52 (0.00%)  0
Metabolism and nutrition disorders     
Decreased appetite  1  1/52 (1.92%)  1 0/52 (0.00%)  0
Nervous system disorders     
Dizziness  1  1/52 (1.92%)  1 0/52 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Cough  1  1/52 (1.92%)  1 0/52 (0.00%)  0
Skin and subcutaneous tissue disorders     
Hyperhydrosis  1  1/52 (1.92%)  1 0/52 (0.00%)  0
Vascular disorders     
Hypotension  1  4/52 (7.69%)  4 0/52 (0.00%)  0
1
Term from vocabulary, MedDRA (21.0)
Indicates events were collected by systematic assessment
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Robert Mentz
Organization: Duke Clinical Research Institute
Phone: 919-668-7121
EMail: robert.mentz@duke.edu
Layout table for additonal information
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT02827500    
Other Study ID Numbers: Pro00071309
First Submitted: July 6, 2016
First Posted: July 11, 2016
Results First Submitted: September 12, 2019
Results First Posted: October 1, 2019
Last Update Posted: October 1, 2019