Trial Outcomes & Findings for Safety Study of Pyridostigmine in Heart Failure (NCT NCT01415921)
NCT ID: NCT01415921
Last Updated: 2017-07-31
Results Overview
Change in peak HR at end of exercise to 1 minute post-exercise (beats per minute)
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
33 participants
Primary outcome timeframe
Baseline
Results posted on
2017-07-31
Participant Flow
Admissions logs and other existing electronic hospital information systems
Participant milestones
| Measure |
Pyridostigmine Bromide
Forced titration protocol 15-60 mg every 8 hours as tolerated
Pyridostigmine Bromide: 15, 30, and 60 mg tabs, 1 tab every 8 hours for 10 weeks. Forced titration protocol increases dose at 2 week intervals from 15 to 30 to 60 mg as tolerated. Continue maximally tolerated dose for 4 weeks and then downtitrate at weekly intervals (60 to 30 to 15) and then discontinue.
|
Placebo
Matching placebo forced titration 15-60 mg as tolerated
Pyridostigmine Bromide: 15, 30, and 60 mg tabs, 1 tab every 8 hours for 10 weeks. Forced titration protocol increases dose at 2 week intervals from 15 to 30 to 60 mg as tolerated. Continue maximally tolerated dose for 4 weeks and then downtitrate at weekly intervals (60 to 30 to 15) and then discontinue.
|
|---|---|---|
|
Overall Study
STARTED
|
16
|
17
|
|
Overall Study
COMPLETED
|
13
|
14
|
|
Overall Study
NOT COMPLETED
|
3
|
3
|
Reasons for withdrawal
| Measure |
Pyridostigmine Bromide
Forced titration protocol 15-60 mg every 8 hours as tolerated
Pyridostigmine Bromide: 15, 30, and 60 mg tabs, 1 tab every 8 hours for 10 weeks. Forced titration protocol increases dose at 2 week intervals from 15 to 30 to 60 mg as tolerated. Continue maximally tolerated dose for 4 weeks and then downtitrate at weekly intervals (60 to 30 to 15) and then discontinue.
|
Placebo
Matching placebo forced titration 15-60 mg as tolerated
Pyridostigmine Bromide: 15, 30, and 60 mg tabs, 1 tab every 8 hours for 10 weeks. Forced titration protocol increases dose at 2 week intervals from 15 to 30 to 60 mg as tolerated. Continue maximally tolerated dose for 4 weeks and then downtitrate at weekly intervals (60 to 30 to 15) and then discontinue.
|
|---|---|---|
|
Overall Study
Adverse Event
|
0
|
1
|
|
Overall Study
Physician Decision
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
|
Overall Study
Other
|
2
|
0
|
Baseline Characteristics
Safety Study of Pyridostigmine in Heart Failure
Baseline characteristics by cohort
| Measure |
Pyridostigmine Bromide
n=16 Participants
Forced titration protocol 15-60 mg every 8 hours as tolerated
Pyridostigmine Bromide: 15, 30, and 60 mg tabs, 1 tab every 8 hours for 10 weeks. Forced titration protocol increases dose at 2 week intervals from 15 to 30 to 60 mg as tolerated. Continue maximally tolerated dose for 4 weeks and then downtitrate at weekly intervals (60 to 30 to 15) and then discontinue.
|
Placebo
n=17 Participants
Matching placebo forced titration 15-60 mg as tolerated
Pyridostigmine Bromide: 15, 30, and 60 mg tabs, 1 tab every 8 hours for 10 weeks. Forced titration protocol increases dose at 2 week intervals from 15 to 30 to 60 mg as tolerated. Continue maximally tolerated dose for 4 weeks and then downtitrate at weekly intervals (60 to 30 to 15) and then discontinue.
|
Total
n=33 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
14 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
8 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
16 participants
n=5 Participants
|
17 participants
n=7 Participants
|
33 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: BaselinePopulation: Heart rate recovery is also measured as beats/min (peak HR at end of exercise - HR 1 min post exercise = HRR).
Change in peak HR at end of exercise to 1 minute post-exercise (beats per minute)
Outcome measures
| Measure |
Placebo
n=14 Participants
Matching placebo forced titration 15-60 mg as tolerated
Pyridostigmine Bromide: 15, 30, and 60 mg tabs, 1 tab every 8 hours for 10 weeks. Forced titration protocol increases dose at 2 week intervals from 15 to 30 to 60 mg as tolerated. Continue maximally tolerated dose for 4 weeks and then downtitrate at weekly intervals (60 to 30 to 15) and then discontinue.
|
Pyridostigmine Bromide
n=13 Participants
Forced titration protocol 15-60 mg every 8 hours as tolerated
Pyridostigmine Bromide: 15, 30, and 60 mg tabs, 1 tab every 8 hours for 10 weeks. Forced titration protocol increases dose at 2 week intervals from 15 to 30 to 60 mg as tolerated. Continue maximally tolerated dose for 4 weeks and then downtitrate at weekly intervals (60 to 30 to 15) and then discontinue.
|
|---|---|---|
|
Baseline Heart Rate Recovery
|
30.4 beats per minute
Standard Deviation 14.8
|
32.5 beats per minute
Standard Deviation 12.8
|
PRIMARY outcome
Timeframe: 12 weeksPopulation: Heart rate recovery is also measured as beats/min (peak HR at end of exercise - HR 1 min post exercise = HRR).
Change in heart rate from peak exercise to 1 minute post-exercise (beats per minute)
Outcome measures
| Measure |
Placebo
n=14 Participants
Matching placebo forced titration 15-60 mg as tolerated
Pyridostigmine Bromide: 15, 30, and 60 mg tabs, 1 tab every 8 hours for 10 weeks. Forced titration protocol increases dose at 2 week intervals from 15 to 30 to 60 mg as tolerated. Continue maximally tolerated dose for 4 weeks and then downtitrate at weekly intervals (60 to 30 to 15) and then discontinue.
|
Pyridostigmine Bromide
n=13 Participants
Forced titration protocol 15-60 mg every 8 hours as tolerated
Pyridostigmine Bromide: 15, 30, and 60 mg tabs, 1 tab every 8 hours for 10 weeks. Forced titration protocol increases dose at 2 week intervals from 15 to 30 to 60 mg as tolerated. Continue maximally tolerated dose for 4 weeks and then downtitrate at weekly intervals (60 to 30 to 15) and then discontinue.
|
|---|---|---|
|
Post Exercise Heart Rate Recovery
|
34.9 beats per minute
Standard Deviation 16.1
|
38.5 beats per minute
Standard Deviation 12.2
|
Adverse Events
Pyridostigmine Bromide
Serious events: 2 serious events
Other events: 11 other events
Deaths: 0 deaths
Placebo
Serious events: 3 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Pyridostigmine Bromide
n=16 participants at risk
Forced titration protocol 15-60 mg every 8 hours as tolerated
Pyridostigmine Bromide: 15, 30, and 60 mg tabs, 1 tab every 8 hours for 10 weeks. Forced titration protocol increases dose at 2 week intervals from 15 to 30 to 60 mg as tolerated. Continue maximally tolerated dose for 4 weeks and then downtitrate at weekly intervals (60 to 30 to 15) and then discontinue.
|
Placebo
n=17 participants at risk
Matching placebo forced titration 15-60 mg as tolerated
Pyridostigmine Bromide: 15, 30, and 60 mg tabs, 1 tab every 8 hours for 10 weeks. Forced titration protocol increases dose at 2 week intervals from 15 to 30 to 60 mg as tolerated. Continue maximally tolerated dose for 4 weeks and then downtitrate at weekly intervals (60 to 30 to 15) and then discontinue.
|
|---|---|---|
|
Cardiac disorders
Decompensated Heart Failure
|
0.00%
0/16
|
5.9%
1/17 • Number of events 1
|
|
Cardiac disorders
Elective Stent Placement
|
0.00%
0/16
|
5.9%
1/17 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal Paim
|
6.2%
1/16 • Number of events 1
|
0.00%
0/17
|
|
General disorders
Fever
|
6.2%
1/16 • Number of events 1
|
0.00%
0/17
|
|
Cardiac disorders
Ventricular Malposition of an ICD Lead
|
0.00%
0/16
|
5.9%
1/17 • Number of events 1
|
Other adverse events
| Measure |
Pyridostigmine Bromide
n=16 participants at risk
Forced titration protocol 15-60 mg every 8 hours as tolerated
Pyridostigmine Bromide: 15, 30, and 60 mg tabs, 1 tab every 8 hours for 10 weeks. Forced titration protocol increases dose at 2 week intervals from 15 to 30 to 60 mg as tolerated. Continue maximally tolerated dose for 4 weeks and then downtitrate at weekly intervals (60 to 30 to 15) and then discontinue.
|
Placebo
n=17 participants at risk
Matching placebo forced titration 15-60 mg as tolerated
Pyridostigmine Bromide: 15, 30, and 60 mg tabs, 1 tab every 8 hours for 10 weeks. Forced titration protocol increases dose at 2 week intervals from 15 to 30 to 60 mg as tolerated. Continue maximally tolerated dose for 4 weeks and then downtitrate at weekly intervals (60 to 30 to 15) and then discontinue.
|
|---|---|---|
|
Blood and lymphatic system disorders
Leukocytosis
|
6.2%
1/16 • Number of events 1
|
0.00%
0/17
|
|
Cardiac disorders
Chest Pain
|
6.2%
1/16 • Number of events 1
|
0.00%
0/17
|
|
Eye disorders
Blurred vision of right eye
|
0.00%
0/16
|
5.9%
1/17 • Number of events 1
|
|
Gastrointestinal disorders
Loose Stools
|
12.5%
2/16 • Number of events 2
|
5.9%
1/17 • Number of events 1
|
|
Gastrointestinal disorders
Flatulence
|
12.5%
2/16 • Number of events 2
|
0.00%
0/17
|
|
Gastrointestinal disorders
Diarrhea
|
31.2%
5/16 • Number of events 5
|
11.8%
2/17 • Number of events 2
|
|
Gastrointestinal disorders
Bloating
|
6.2%
1/16 • Number of events 1
|
0.00%
0/17
|
|
Gastrointestinal disorders
Abdominal Pain
|
12.5%
2/16 • Number of events 2
|
5.9%
1/17 • Number of events 1
|
|
Gastrointestinal disorders
Black Stool
|
6.2%
1/16 • Number of events 1
|
0.00%
0/17
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/16
|
5.9%
1/17 • Number of events 1
|
|
General disorders
Flu like symptoms
|
6.2%
1/16 • Number of events 1
|
0.00%
0/17
|
|
General disorders
Fatigue
|
6.2%
1/16 • Number of events 1
|
0.00%
0/17
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/16
|
5.9%
1/17 • Number of events 1
|
|
Infections and infestations
Cellulitis
|
0.00%
0/16
|
5.9%
1/17 • Number of events 1
|
|
Injury, poisoning and procedural complications
Ankle sprain
|
6.2%
1/16 • Number of events 1
|
0.00%
0/17
|
|
Investigations
Pacemaker AMS
|
6.2%
1/16 • Number of events 1
|
0.00%
0/17
|
|
Investigations
Inadequate ICD shock
|
0.00%
0/16
|
5.9%
1/17 • Number of events 1
|
|
Investigations
Ventricular pacing
|
0.00%
0/16
|
5.9%
1/17 • Number of events 1
|
|
Investigations
Supraventicular tachycardia reported on ICD
|
0.00%
0/16
|
5.9%
1/17 • Number of events 1
|
|
Investigations
Total Bilirubin Increased
|
0.00%
0/16
|
5.9%
1/17 • Number of events 1
|
|
Investigations
Elevated Alkaline Phosphatase
|
6.2%
1/16 • Number of events 1
|
0.00%
0/17
|
|
Investigations
Elevated hepatic enzymes
|
0.00%
0/16
|
5.9%
1/17 • Number of events 1
|
|
Investigations
Thrombocitopenia
|
0.00%
0/16
|
5.9%
1/17 • Number of events 1
|
|
Investigations
Percent Eosinophils Increased
|
6.2%
1/16 • Number of events 1
|
0.00%
0/17
|
|
Investigations
PMT (Pacemaker Tachycardia)
|
6.2%
1/16 • Number of events 1
|
0.00%
0/17
|
|
Musculoskeletal and connective tissue disorders
Pain in lower extremities
|
6.2%
1/16 • Number of events 1
|
0.00%
0/17
|
|
Musculoskeletal and connective tissue disorders
Tendinitis
|
6.2%
1/16 • Number of events 1
|
0.00%
0/17
|
|
Musculoskeletal and connective tissue disorders
Plantar Fasciitis
|
6.2%
1/16 • Number of events 1
|
0.00%
0/17
|
|
Musculoskeletal and connective tissue disorders
Gout
|
0.00%
0/16
|
5.9%
1/17 • Number of events 1
|
|
Nervous system disorders
Dizziness
|
6.2%
1/16 • Number of events 1
|
5.9%
1/17 • Number of events 1
|
|
Renal and urinary disorders
Urinary Incontinence
|
6.2%
1/16 • Number of events 1
|
0.00%
0/17
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
6.2%
1/16 • Number of events 1
|
0.00%
0/17
|
|
Skin and subcutaneous tissue disorders
Sweating
|
0.00%
0/16
|
5.9%
1/17 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/16
|
5.9%
1/17 • Number of events 1
|
|
Vascular disorders
Low heart rate
|
6.2%
1/16 • Number of events 1
|
5.9%
1/17 • Number of events 1
|
|
Vascular disorders
Hypertension
|
0.00%
0/16
|
11.8%
2/17 • Number of events 2
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place