Trial Outcomes & Findings for Pilot of Zinc Acetate to Improve Chronic Cough (NCT NCT03135522)
NCT ID: NCT03135522
Last Updated: 2021-01-20
Results Overview
Unadjusted comparison of change in CQLQ score between zinc acetate and placebo treatment groups. CQLQ scores range from 28 to 112, with lower scores indicating fewer adverse events. A minimum clinically importance difference of 5 has been proposed for this questionnaire.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
34 participants
Primary outcome timeframe
Baseline and 6 weeks
Results posted on
2021-01-20
Participant Flow
Participant milestones
| Measure |
Zinc Acetate 50 mg Oral Capsule
50 mg zinc acetate oral capsules, over-encapsulated, administered starting at 1 capsule/day and escalated to 3 capsules/day by Day 8 post-randomization (if tolerated)
Zinc Acetate 50 Mg Oral Capsule: • Day 0 (randomization) to day 3 Zinc acetate 50 mg per day (one capsule)
* Day 4 to day 7 If well tolerated: Zinc acetate 100 mg per day (two capsules)
* Day 8 to V5 (6 weeks) If well tolerated: Zinc acetate 150 mg per day (three capsules)
|
Placebo Oral Capsule
Placebo matched to zinc acetate 50 mg oral capsule active arm, administered starting at 1 capsule/day and escalated to 3 capsules/day by Day 8 post-randomization (if tolerated)
Placebo oral capsule: • Day 0 (randomization) to day 3 Placebo (one capsule per day)
* Day 4 to day 7 If well tolerated: placebo (two capsules per day)
* Day 8 to V5 (6 weeks) If well tolerated: placebo (three capsules per day)
|
|---|---|---|
|
Overall Study
STARTED
|
17
|
17
|
|
Overall Study
COMPLETED
|
16
|
17
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
Zinc Acetate 50 mg Oral Capsule
50 mg zinc acetate oral capsules, over-encapsulated, administered starting at 1 capsule/day and escalated to 3 capsules/day by Day 8 post-randomization (if tolerated)
Zinc Acetate 50 Mg Oral Capsule: • Day 0 (randomization) to day 3 Zinc acetate 50 mg per day (one capsule)
* Day 4 to day 7 If well tolerated: Zinc acetate 100 mg per day (two capsules)
* Day 8 to V5 (6 weeks) If well tolerated: Zinc acetate 150 mg per day (three capsules)
|
Placebo Oral Capsule
Placebo matched to zinc acetate 50 mg oral capsule active arm, administered starting at 1 capsule/day and escalated to 3 capsules/day by Day 8 post-randomization (if tolerated)
Placebo oral capsule: • Day 0 (randomization) to day 3 Placebo (one capsule per day)
* Day 4 to day 7 If well tolerated: placebo (two capsules per day)
* Day 8 to V5 (6 weeks) If well tolerated: placebo (three capsules per day)
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
Baseline Characteristics
Pilot of Zinc Acetate to Improve Chronic Cough
Baseline characteristics by cohort
| Measure |
Zinc Acetate 50 mg Oral Capsule
n=17 Participants
50 mg zinc acetate oral capsules, over-encapsulated, administered starting at 1 capsule/day and escalated to 3 capsules/day by Day 8 post-randomization (if tolerated)
Zinc Acetate 50 Mg Oral Capsule: • Day 0 (randomization) to day 3 Zinc acetate 50 mg per day (one capsule)
* Day 4 to day 7 If well tolerated: Zinc acetate 100 mg per day (two capsules)
* Day 8 to V5 (6 weeks) If well tolerated: Zinc acetate 150 mg per day (three capsules)
|
Placebo Oral Capsule
n=17 Participants
Placebo matched to zinc acetate 50 mg oral capsule active arm, administered starting at 1 capsule/day and escalated to 3 capsules/day by Day 8 post-randomization (if tolerated)
Placebo oral capsule: • Day 0 (randomization) to day 3 Placebo (one capsule per day)
* Day 4 to day 7 If well tolerated: placebo (two capsules per day)
* Day 8 to V5 (6 weeks) If well tolerated: placebo (three capsules per day)
|
Total
n=34 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
62 years
n=99 Participants
|
62 years
n=107 Participants
|
62 years
n=206 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=99 Participants
|
16 Participants
n=107 Participants
|
28 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
15 Participants
n=99 Participants
|
15 Participants
n=107 Participants
|
30 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
14 Participants
n=99 Participants
|
14 Participants
n=107 Participants
|
28 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
17 Participants
n=99 Participants
|
17 Participants
n=107 Participants
|
34 Participants
n=206 Participants
|
|
Smoking Status
Former
|
2 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
|
Smoking Status
Never
|
15 Participants
n=99 Participants
|
14 Participants
n=107 Participants
|
29 Participants
n=206 Participants
|
|
E-cigarette usage
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Household Income, yearly
Less than $30,000
|
4 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
7 Participants
n=206 Participants
|
|
Household Income, yearly
$30,001 - 50,000
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Household Income, yearly
$50,001 - 75,000
|
3 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
|
Household Income, yearly
Over $75,000
|
6 Participants
n=99 Participants
|
12 Participants
n=107 Participants
|
18 Participants
n=206 Participants
|
|
Household Income, yearly
Declined to answer
|
4 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Highest level of education completed
More than eighth grade but not high school grad
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Highest level of education completed
High school graduate or equivalent
|
3 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Highest level of education completed
Some college
|
2 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
|
Highest level of education completed
Graduate of two year college or technical school
|
3 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
|
Highest level of education completed
Graduate of four-year college
|
3 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
11 Participants
n=206 Participants
|
|
Highest level of education completed
Post-graduate studies
|
6 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
10 Participants
n=206 Participants
|
|
Health insurance
Private insurance
|
11 Participants
n=99 Participants
|
14 Participants
n=107 Participants
|
25 Participants
n=206 Participants
|
|
Health insurance
Public insurance
|
5 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
|
Health insurance
Don't know
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Cough characteristics
Cough upon awakening
|
11 Participants
n=99 Participants
|
12 Participants
n=107 Participants
|
23 Participants
n=206 Participants
|
|
Cough characteristics
Cough during the rest of the day or night
|
17 Participants
n=99 Participants
|
16 Participants
n=107 Participants
|
33 Participants
n=206 Participants
|
|
Cough characteristics
Persistent phlegm in chest
|
7 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
|
Frequency of cough
Almost every day
|
14 Participants
n=99 Participants
|
16 Participants
n=107 Participants
|
30 Participants
n=206 Participants
|
|
Frequency of cough
Several days a week
|
3 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Has asthma based on spirometry or methacholine challenge
|
8 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
14 Participants
n=206 Participants
|
|
Has gastroesophageal reflux disease based on diagnosis or a positive pH probe
|
10 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
20 Participants
n=206 Participants
|
|
Has rhinosinusitis, postnasal drip, and/or upper airway disease
|
14 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
20 Participants
n=206 Participants
|
|
Cough medications
Cough suppressants
|
4 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
7 Participants
n=206 Participants
|
|
Cough medications
Benzonatate
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Cough medications
Other cough medications
|
0 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
|
Cough medications
None of the above
|
12 Participants
n=99 Participants
|
11 Participants
n=107 Participants
|
23 Participants
n=206 Participants
|
|
Breathing medications
Bronchodilators
|
7 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
13 Participants
n=206 Participants
|
|
Breathing medications
Inhaled corticosteroids
|
1 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Breathing medications
Other medications for breathing
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Breathing medications
None of the above
|
8 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
18 Participants
n=206 Participants
|
|
Acid reflux medications
Proton pump inhibitors
|
5 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
|
Acid reflux medications
Histamine 2 receptor blockers
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Acid reflux medications
Other acid reflux medications
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Acid reflux medications
None of the above
|
11 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
21 Participants
n=206 Participants
|
|
Rhinosinusitis medications
Nasal steroids
|
8 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
13 Participants
n=206 Participants
|
|
Rhinosinusitis medications
Oral antihistamines
|
2 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Rhinosinusitis medications
Other runny nose or postnasal drip medications
|
3 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Rhinosinusitis medications
None of the above
|
4 Participants
n=99 Participants
|
11 Participants
n=107 Participants
|
15 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline and 6 weeksUnadjusted comparison of change in CQLQ score between zinc acetate and placebo treatment groups. CQLQ scores range from 28 to 112, with lower scores indicating fewer adverse events. A minimum clinically importance difference of 5 has been proposed for this questionnaire.
Outcome measures
| Measure |
Zinc Acetate 50 mg Oral Capsule
n=17 Participants
50 mg zinc acetate oral capsules, over-encapsulated, administered starting at 1 capsule/day and escalated to 3 capsules/day by Day 8 post-randomization (if tolerated)
Zinc Acetate 50 Mg Oral Capsule: • Day 0 (randomization) to day 3 Zinc acetate 50 mg per day (one capsule)
* Day 4 to day 7 If well tolerated: Zinc acetate 100 mg per day (two capsules)
* Day 8 to V5 (6 weeks) If well tolerated: Zinc acetate 150 mg per day (three capsules)
|
Placebo Oral Capsule
n=17 Participants
Placebo matched to zinc acetate 50 mg oral capsule active arm, administered starting at 1 capsule/day and escalated to 3 capsules/day by Day 8 post-randomization (if tolerated)
Placebo oral capsule: • Day 0 (randomization) to day 3 Placebo (one capsule per day)
* Day 4 to day 7 If well tolerated: placebo (two capsules per day)
* Day 8 to V5 (6 weeks) If well tolerated: placebo (three capsules per day)
|
|---|---|---|
|
Change in Cough Quality of Life Questionnaire (CQLQ) Score by Treatment Group
|
-5.00 score on a scale
Interval -14.0 to 0.0
|
-6.00 score on a scale
Interval -18.0 to 0.0
|
SECONDARY outcome
Timeframe: Baseline and 6 weeksUnadjusted comparison of change in LCQ scores between zinc acetate and placebo treatment groups. LCQ scores range from 3 to 21, with lower scores indicating a greater impact of cough upon one's life. The minimum clinically importance difference for the LCQ for people with chronic cough is 1.3.
Outcome measures
| Measure |
Zinc Acetate 50 mg Oral Capsule
n=17 Participants
50 mg zinc acetate oral capsules, over-encapsulated, administered starting at 1 capsule/day and escalated to 3 capsules/day by Day 8 post-randomization (if tolerated)
Zinc Acetate 50 Mg Oral Capsule: • Day 0 (randomization) to day 3 Zinc acetate 50 mg per day (one capsule)
* Day 4 to day 7 If well tolerated: Zinc acetate 100 mg per day (two capsules)
* Day 8 to V5 (6 weeks) If well tolerated: Zinc acetate 150 mg per day (three capsules)
|
Placebo Oral Capsule
n=17 Participants
Placebo matched to zinc acetate 50 mg oral capsule active arm, administered starting at 1 capsule/day and escalated to 3 capsules/day by Day 8 post-randomization (if tolerated)
Placebo oral capsule: • Day 0 (randomization) to day 3 Placebo (one capsule per day)
* Day 4 to day 7 If well tolerated: placebo (two capsules per day)
* Day 8 to V5 (6 weeks) If well tolerated: placebo (three capsules per day)
|
|---|---|---|
|
Change in Leicester Cough Questionnaire (LCQ) Score by Treatment Group
|
2.55 score on a scale
Interval 1.16 to 4.13
|
2.59 score on a scale
Interval 0.52 to 5.04
|
SECONDARY outcome
Timeframe: Baseline and 6 weeksUnadjusted comparison of change in overall severity of cough as measured by C-VAS between zinc acetate and placebo treatment groups. C-VAS scores cover four domains - severity of cough in daytime, nighttime, and overall, and severity of urge to cough. Scores range from 0 to 100 for each domain with overall scores ranging from 0 to 400. Lower scores indicate less severity. Overall severity of cough is the only domain reported here.
Outcome measures
| Measure |
Zinc Acetate 50 mg Oral Capsule
n=17 Participants
50 mg zinc acetate oral capsules, over-encapsulated, administered starting at 1 capsule/day and escalated to 3 capsules/day by Day 8 post-randomization (if tolerated)
Zinc Acetate 50 Mg Oral Capsule: • Day 0 (randomization) to day 3 Zinc acetate 50 mg per day (one capsule)
* Day 4 to day 7 If well tolerated: Zinc acetate 100 mg per day (two capsules)
* Day 8 to V5 (6 weeks) If well tolerated: Zinc acetate 150 mg per day (three capsules)
|
Placebo Oral Capsule
n=17 Participants
Placebo matched to zinc acetate 50 mg oral capsule active arm, administered starting at 1 capsule/day and escalated to 3 capsules/day by Day 8 post-randomization (if tolerated)
Placebo oral capsule: • Day 0 (randomization) to day 3 Placebo (one capsule per day)
* Day 4 to day 7 If well tolerated: placebo (two capsules per day)
* Day 8 to V5 (6 weeks) If well tolerated: placebo (three capsules per day)
|
|---|---|---|
|
Change in Cough Visual Assessment Scale (C-VAS) Scores by Treatment Group
|
-15.24 score on a scale
Interval -32.0 to -0.99
|
-17.82 score on a scale
Interval -29.52 to -7.62
|
SECONDARY outcome
Timeframe: Baseline and 6 weeksUnadjusted comparison of change in GACC scores between zinc acetate and placebo treatment groups. GACC scores measure change in quality of life related to cough in four domains - activity limitation, symptoms, emotions, and overall quality of life. GACC scores range from -3 (very much worse) to 3 (very much better).
Outcome measures
| Measure |
Zinc Acetate 50 mg Oral Capsule
n=17 Participants
50 mg zinc acetate oral capsules, over-encapsulated, administered starting at 1 capsule/day and escalated to 3 capsules/day by Day 8 post-randomization (if tolerated)
Zinc Acetate 50 Mg Oral Capsule: • Day 0 (randomization) to day 3 Zinc acetate 50 mg per day (one capsule)
* Day 4 to day 7 If well tolerated: Zinc acetate 100 mg per day (two capsules)
* Day 8 to V5 (6 weeks) If well tolerated: Zinc acetate 150 mg per day (three capsules)
|
Placebo Oral Capsule
n=17 Participants
Placebo matched to zinc acetate 50 mg oral capsule active arm, administered starting at 1 capsule/day and escalated to 3 capsules/day by Day 8 post-randomization (if tolerated)
Placebo oral capsule: • Day 0 (randomization) to day 3 Placebo (one capsule per day)
* Day 4 to day 7 If well tolerated: placebo (two capsules per day)
* Day 8 to V5 (6 weeks) If well tolerated: placebo (three capsules per day)
|
|---|---|---|
|
Change in Global Assessment of Change in Cough (GACC) Score by Treatment Group
|
0.50 score on a scale
Interval 0.0 to 1.25
|
0.25 score on a scale
Interval 0.0 to 0.75
|
Adverse Events
Zinc Acetate 50 mg Oral Capsule
Serious events: 2 serious events
Other events: 1 other events
Deaths: 0 deaths
Placebo Oral Capsule
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Zinc Acetate 50 mg Oral Capsule
n=17 participants at risk
50 mg zinc acetate oral capsules, over-encapsulated, administered starting at 1 capsule/day and escalated to 3 capsules/day by Day 8 post-randomization (if tolerated)
Zinc Acetate 50 Mg Oral Capsule: • Day 0 (randomization) to day 3 Zinc acetate 50 mg per day (one capsule)
* Day 4 to day 7 If well tolerated: Zinc acetate 100 mg per day (two capsules)
* Day 8 to V5 (6 weeks) If well tolerated: Zinc acetate 150 mg per day (three capsules)
|
Placebo Oral Capsule
n=17 participants at risk
Placebo matched to zinc acetate 50 mg oral capsule active arm, administered starting at 1 capsule/day and escalated to 3 capsules/day by Day 8 post-randomization (if tolerated)
Placebo oral capsule: • Day 0 (randomization) to day 3 Placebo (one capsule per day)
* Day 4 to day 7 If well tolerated: placebo (two capsules per day)
* Day 8 to V5 (6 weeks) If well tolerated: placebo (three capsules per day)
|
|---|---|---|
|
Gastrointestinal disorders
Pancreatitis
|
5.9%
1/17 • Number of events 1 • 10 weeks
|
0.00%
0/17 • 10 weeks
|
|
Musculoskeletal and connective tissue disorders
Herniated disc
|
5.9%
1/17 • Number of events 1 • 10 weeks
|
0.00%
0/17 • 10 weeks
|
|
Renal and urinary disorders
Urosepsis
|
0.00%
0/17 • 10 weeks
|
5.9%
1/17 • Number of events 1 • 10 weeks
|
Other adverse events
| Measure |
Zinc Acetate 50 mg Oral Capsule
n=17 participants at risk
50 mg zinc acetate oral capsules, over-encapsulated, administered starting at 1 capsule/day and escalated to 3 capsules/day by Day 8 post-randomization (if tolerated)
Zinc Acetate 50 Mg Oral Capsule: • Day 0 (randomization) to day 3 Zinc acetate 50 mg per day (one capsule)
* Day 4 to day 7 If well tolerated: Zinc acetate 100 mg per day (two capsules)
* Day 8 to V5 (6 weeks) If well tolerated: Zinc acetate 150 mg per day (three capsules)
|
Placebo Oral Capsule
n=17 participants at risk
Placebo matched to zinc acetate 50 mg oral capsule active arm, administered starting at 1 capsule/day and escalated to 3 capsules/day by Day 8 post-randomization (if tolerated)
Placebo oral capsule: • Day 0 (randomization) to day 3 Placebo (one capsule per day)
* Day 4 to day 7 If well tolerated: placebo (two capsules per day)
* Day 8 to V5 (6 weeks) If well tolerated: placebo (three capsules per day)
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Skin rash
|
5.9%
1/17 • Number of events 1 • 10 weeks
|
0.00%
0/17 • 10 weeks
|
|
Blood and lymphatic system disorders
Elevated copper level
|
0.00%
0/17 • 10 weeks
|
11.8%
2/17 • Number of events 2 • 10 weeks
|
Additional Information
Dr. Robert A. Wise, M.D.
The Johns Hopkins University School of Medicine
Phone: 410-905-5688
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place