Trial Outcomes & Findings for Comparison of Two Macrolides, Azithromycin and Erythromycin, for Symptomatic Treatment of Gastroparesis (NCT NCT01323582)
NCT ID: NCT01323582
Last Updated: 2014-12-05
Results Overview
Patients will be given a standardized meal enriched with a labeled material and the breath samples are then collected and analyzed. The estimated time to empty 50% (t 1/2) of the accumulated contents is recorded. Because the difference is RX-B -RX A in one group and RX A -RX B in the other, the difference between these two estimates twice the effect size. Hence the Half is applied, as is standard in the two sample method for crossover studies.
TERMINATED
PHASE2
26 participants
Weeks 4 and 11 (end of periods)
2014-12-05
Participant Flow
Participant milestones
| Measure |
Erythromycin First Then Azithromycin
Erythromycin is given for 4 weeks (1-4), there is a 3 week washout (5-7), then Azithromycin is given for 4 weeks (Weeks 8-11).
|
Azithromycin Then Erythromycin
Azithromycin is given for 4 weeks (1-4), there is a 3 week washout (5-7), then Erythromycin is given for 4 weeks (Weeks 8-11).
|
|---|---|---|
|
Weeks 1-4 (First Period)
STARTED
|
12
|
14
|
|
Weeks 1-4 (First Period)
COMPLETED
|
10
|
12
|
|
Weeks 1-4 (First Period)
NOT COMPLETED
|
2
|
2
|
|
Weeks 5-7 (Washout)
STARTED
|
10
|
12
|
|
Weeks 5-7 (Washout)
COMPLETED
|
10
|
11
|
|
Weeks 5-7 (Washout)
NOT COMPLETED
|
0
|
1
|
|
Weeks 8-11 (Period 2)
STARTED
|
10
|
11
|
|
Weeks 8-11 (Period 2)
COMPLETED
|
10
|
10
|
|
Weeks 8-11 (Period 2)
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
Erythromycin First Then Azithromycin
Erythromycin is given for 4 weeks (1-4), there is a 3 week washout (5-7), then Azithromycin is given for 4 weeks (Weeks 8-11).
|
Azithromycin Then Erythromycin
Azithromycin is given for 4 weeks (1-4), there is a 3 week washout (5-7), then Erythromycin is given for 4 weeks (Weeks 8-11).
|
|---|---|---|
|
Weeks 1-4 (First Period)
Withdrawal by Subject
|
2
|
2
|
|
Weeks 5-7 (Washout)
Withdrawal by Subject
|
0
|
1
|
|
Weeks 8-11 (Period 2)
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
Comparison of Two Macrolides, Azithromycin and Erythromycin, for Symptomatic Treatment of Gastroparesis
Baseline characteristics by cohort
| Measure |
Erythromycin First Then Azithromycin
n=12 Participants
Erythromycin is given for 4 weeks (1-4), there is a 3 week washout (5-7), then Azithromycin is given for 4 weeks (Weeks 8-11).
|
Azithromycin Then Erythromycin
n=14 Participants
Azithromycin is given for 4 weeks (1-4), there is a 3 week washout (5-7), then Erythromycin is given for 4 weeks (Weeks 8-11).
|
Total
n=26 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
46.1 years
STANDARD_DEVIATION 12.7 • n=5 Participants
|
48.5 years
STANDARD_DEVIATION 11.7 • n=7 Participants
|
47.4 years
STANDARD_DEVIATION 12.0 • n=5 Participants
|
|
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
|
12 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
12 participants
n=5 Participants
|
14 participants
n=7 Participants
|
26 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Weeks 4 and 11 (end of periods)Patients will be given a standardized meal enriched with a labeled material and the breath samples are then collected and analyzed. The estimated time to empty 50% (t 1/2) of the accumulated contents is recorded. Because the difference is RX-B -RX A in one group and RX A -RX B in the other, the difference between these two estimates twice the effect size. Hence the Half is applied, as is standard in the two sample method for crossover studies.
Outcome measures
| Measure |
Erythromycin First Then Azithromycin
n=10 Participants
Erythromycin is given for 4 weeks (1-4), there is a 3 week washout (5-7), then Azithromycin is given for 4 weeks (Weeks 8-11).
|
Azithromycin Then Erythromycin
n=10 Participants
Azithromycin is given for 4 weeks (1-4), there is a 3 week washout (5-7), then Erythromycin is given for 4 weeks (Weeks 8-11).
|
|---|---|---|
|
Time in Minutes for 50% of the Ingested Meal to Empty the Stomach With a Standardized Breath Test: Half the of the Week 11 Value (Period 2) Less Half the of the Week 4 Value (Period 1). This Estimates the Effect Size.
|
-1.6 Minutes
Standard Deviation 32.3
|
-5.2 Minutes
Standard Deviation 17.9
|
PRIMARY outcome
Timeframe: Weeks 4 and 11 (end of periods)Population: One subject did not complete this part of analysis.
This is a Validated instrument for measuring symptom severity in patients with gastroparesis. This scoring is based on a Likert Scale from (0-5) with zero being no symptoms and five being very severe symptoms on 9 subscales, making the overall score range from 0-45. The higher the score, the more severe patient's symptoms. Reference for GCSI: Revicki DA, REntz AM, Dubois D, et al. Development and validation of a patient-assessed gastroparesis symptoms severity measure: the Gastroparesis Cardinal Symptom Index. Ailment Pharm Ther 2003; 18: 141:50. Because the difference is RX-B -RX A in one group and RX A -RX B in the other, the difference between these two estimates twice the effect size. Hence the Half is applied, as is standard in the two sample method for crossover studies.
Outcome measures
| Measure |
Erythromycin First Then Azithromycin
n=10 Participants
Erythromycin is given for 4 weeks (1-4), there is a 3 week washout (5-7), then Azithromycin is given for 4 weeks (Weeks 8-11).
|
Azithromycin Then Erythromycin
n=9 Participants
Azithromycin is given for 4 weeks (1-4), there is a 3 week washout (5-7), then Erythromycin is given for 4 weeks (Weeks 8-11).
|
|---|---|---|
|
Gastroparesis Cardinal Symptom Index (GCSI) Score
|
-1.6 units on a scale
Standard Deviation 5.2
|
-2.9 units on a scale
Standard Deviation 7.0
|
SECONDARY outcome
Timeframe: Weeks 4 and 11 (end of periods)Nepean Dyspepsia Index (NDI) is a measure of symptom status and quality of life in functional dyspepsia. This scale is scored using each subscale (Tension, interference with daily activities), Eating/drinking, Knowledge/control, work/study) and adding up the items for each of the five subscale score (2-10). Total score range would be 10-50). For the NDI, a lower number is better meaning the symptom is not effecting quality of life and a higher score closer to 50 is worse meaning it is effecting patients quality of life. Reference: Talley NJ, Verlinden M, Jones M. Quality of life in functional dyspepsia: responsiveness of the Nepean Dyspepsia Index and developement of a new 10-iten short form. Aliment Pharmacol Ther 2001: 15: 207-216. Because the difference is RX-B -RX A in one group and RX A -RX B in the other, the difference between these two estimates twice the effect size. Hence the Half is applied, as is standard in the two sample method for crossover studies.
Outcome measures
| Measure |
Erythromycin First Then Azithromycin
n=10 Participants
Erythromycin is given for 4 weeks (1-4), there is a 3 week washout (5-7), then Azithromycin is given for 4 weeks (Weeks 8-11).
|
Azithromycin Then Erythromycin
n=10 Participants
Azithromycin is given for 4 weeks (1-4), there is a 3 week washout (5-7), then Erythromycin is given for 4 weeks (Weeks 8-11).
|
|---|---|---|
|
NDI Score
|
1.65 units on a scale
Standard Deviation 5.6
|
1.30 units on a scale
Standard Deviation 4.60
|
SECONDARY outcome
Timeframe: Weeks 4 and 11 (end of periods)This is defined as the time from ingestion of the meal to the beginning of the emptying process in minutes. Because the difference is RX-B -RX A in one group and RX A -RX B in the other, the difference between these two estimates twice the effect size. Hence the Half is applied, as is standard in the two sample method for crossover studies.
Outcome measures
| Measure |
Erythromycin First Then Azithromycin
n=10 Participants
Erythromycin is given for 4 weeks (1-4), there is a 3 week washout (5-7), then Azithromycin is given for 4 weeks (Weeks 8-11).
|
Azithromycin Then Erythromycin
n=10 Participants
Azithromycin is given for 4 weeks (1-4), there is a 3 week washout (5-7), then Erythromycin is given for 4 weeks (Weeks 8-11).
|
|---|---|---|
|
TLAG (Time From Ingestion of Meal to Start of Gastric Emptying)
|
-1.71 Minutes
Standard Deviation 16.2
|
-0.22 Minutes
Standard Deviation 8.2
|
SECONDARY outcome
Timeframe: Baseline and end of treatment periodPatients will be given a standardized meal enriched with a labeled material and the breath samples are then collected and analyzed. The estimated time to reaching 50% of the accumulated contents is recorded.
Outcome measures
| Measure |
Erythromycin First Then Azithromycin
n=20 Participants
Erythromycin is given for 4 weeks (1-4), there is a 3 week washout (5-7), then Azithromycin is given for 4 weeks (Weeks 8-11).
|
Azithromycin Then Erythromycin
Azithromycin is given for 4 weeks (1-4), there is a 3 week washout (5-7), then Erythromycin is given for 4 weeks (Weeks 8-11).
|
|---|---|---|
|
Change in Time to 50% Gastric Emptying: Post Test Less Baseline Pooled Over Orderings
|
-11.8 Minutes
Standard Deviation 40.8
|
—
|
SECONDARY outcome
Timeframe: at baseline before initiation of the treatment and after completion of each treatment period.Patients will be given a standardized meal enriched with a labeled material and the breath samples are then collected and analyzed. The estimated time to reaching 50% of the accumulated contents is recorded.
Outcome measures
| Measure |
Erythromycin First Then Azithromycin
n=22 Participants
Erythromycin is given for 4 weeks (1-4), there is a 3 week washout (5-7), then Azithromycin is given for 4 weeks (Weeks 8-11).
|
Azithromycin Then Erythromycin
Azithromycin is given for 4 weeks (1-4), there is a 3 week washout (5-7), then Erythromycin is given for 4 weeks (Weeks 8-11).
|
|---|---|---|
|
Change in Time to 50% Emptying: Post Test Less Baseline Pooled Over Orderings
|
-15.0 minutes
Standard Deviation 31.0
|
—
|
SECONDARY outcome
Timeframe: Baseline and end of treatment periodPopulation: One subject did not complete this part of analysis.
This is a Validated instrument for measuring symptom severity in patients with gastroparesis. This scoring is based on a Likert Scale from (0-5) with zero being no symptom and five being very severe symptoms on 9 subscales, making the overall score range from 0-45. The higher the score, the more severe patient's symptoms are. The scale is reported in the references. The change was calculated by measuring the end of treatment minus baseline GCSI score. Negative value reflects this change.
Outcome measures
| Measure |
Erythromycin First Then Azithromycin
n=19 Participants
Erythromycin is given for 4 weeks (1-4), there is a 3 week washout (5-7), then Azithromycin is given for 4 weeks (Weeks 8-11).
|
Azithromycin Then Erythromycin
Azithromycin is given for 4 weeks (1-4), there is a 3 week washout (5-7), then Erythromycin is given for 4 weeks (Weeks 8-11).
|
|---|---|---|
|
Gastroparesis Cardinal Symptom Index (GCSI) Score Change From Baseline to Post Treatment
|
-5.32 units on a scale
Standard Deviation 8.64
|
—
|
SECONDARY outcome
Timeframe: Baseline and end of treatment periodThis is a Validated instrument for measuring symptom severity in patients with gastroparesis. This scoring is based on a Likert Scale from (0-5) with zero being no symptom and five being very severe symptoms on 9 subscales, making the overall score range from 0-45. The higher the score, the more severe patient's symptoms are. The scale is reported in the references. This is a calculation taken with GCSI score at end of treatment minus baseline. Negative value reflects this change.
Outcome measures
| Measure |
Erythromycin First Then Azithromycin
n=22 Participants
Erythromycin is given for 4 weeks (1-4), there is a 3 week washout (5-7), then Azithromycin is given for 4 weeks (Weeks 8-11).
|
Azithromycin Then Erythromycin
Azithromycin is given for 4 weeks (1-4), there is a 3 week washout (5-7), then Erythromycin is given for 4 weeks (Weeks 8-11).
|
|---|---|---|
|
Does GCSI Score Improve (Lower) on Treatment, Pooling the AZ Patients Over Their Treatment Periods? Endpoint is Difference in Post-test Less Baseline
|
-6.40 units on a scale
Standard Deviation 10.30
|
—
|
Adverse Events
Erythromycin
Azithromycin
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Erythromycin
n=26 participants at risk
200mg/5ml elixir administered orally three times a day half an hour prior to meals.
Erythromycin: 200mg/5ml elixir administered orally three times a day half an hour prior to meals.
|
Azithromycin
n=26 participants at risk
The dose of Azithromycin given was previously determined based on our dose-response analysis in 10 healthy subjects to be 50 mg. The total daily dosage of Azithromycin given therefore was 150 mg which was divided three times daily and administered as 50mg/5ml given three times a day as elixir orally, similar to the erythromycin volume.
|
|---|---|---|
|
Gastrointestinal disorders
abdominal pain
|
3.8%
1/26
|
11.5%
3/26
|
|
Gastrointestinal disorders
nausea
|
0.00%
0/26
|
11.5%
3/26
|
|
Gastrointestinal disorders
vomiting
|
0.00%
0/26
|
7.7%
2/26
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place