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Trial record 7 of 180 for:    ERYTHROMYCIN

Comparison of Two Macrolides, Azithromycin and Erythromycin, for Symptomatic Treatment of Gastroparesis (AZI)

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ClinicalTrials.gov Identifier: NCT01323582
Recruitment Status : Terminated (Original investigator left this institution, replacement investigator retired.)
First Posted : March 25, 2011
Results First Posted : December 5, 2014
Last Update Posted : December 5, 2014
Sponsor:
Collaborator:
Metabolic Solutions Inc.
Information provided by (Responsible Party):
University of Florida

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Gastroparesis
Interventions Drug: Erythromycin
Drug: Azithromycin
Enrollment 26
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Erythromycin First Then Azithromycin Azithromycin Then Erythromycin
Hide Arm/Group Description 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 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).
Period Title: Weeks 1-4 (First Period)
Started 12 14
Completed 10 12
Not Completed 2 2
Reason Not Completed
Withdrawal by Subject             2             2
Period Title: Weeks 5-7 (Washout)
Started 10 12
Completed 10 11
Not Completed 0 1
Reason Not Completed
Withdrawal by Subject             0             1
Period Title: Weeks 8-11 (Period 2)
Started 10 11
Completed 10 10
Not Completed 0 1
Reason Not Completed
Withdrawal by Subject             0             1
Arm/Group Title Erythromycin First Then Azithromycin Azithromycin Then Erythromycin Total
Hide Arm/Group Description 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 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 of all reporting groups
Overall Number of Baseline Participants 12 14 26
Hide Baseline Analysis Population Description
These are all subjects who were screened, randomized, and entered the protocol.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 12 participants 14 participants 26 participants
46.1  (12.7) 48.5  (11.7) 47.4  (12.0)
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 14 participants 26 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
12
 100.0%
13
  92.9%
25
  96.2%
>=65 years
0
   0.0%
1
   7.1%
1
   3.8%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 14 participants 26 participants
Female
11
  91.7%
12
  85.7%
23
  88.5%
Male
1
   8.3%
2
  14.3%
3
  11.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 12 participants 14 participants 26 participants
12 14 26
1.Primary Outcome
Title 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.
Hide Description 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.
Time Frame Weeks 4 and 11 (end of periods)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Erythromycin First Then Azithromycin Azithromycin Then Erythromycin
Hide Arm/Group Description:
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 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).
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: Minutes
-1.6  (32.3) -5.2  (17.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Erythromycin First Then Azithromycin, Azithromycin Then Erythromycin
Comments Study planned to accrue 50 subjects, but due to difficult recruitment was not able to meet its objective.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.76
Comments [Not Specified]
Method t-test, 2 sided
Comments Satterthwaite corrected t-test was used
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 3.6
Confidence Interval (2-Sided) 95%
-21.5 to 28.6
Parameter Dispersion
Type: Standard Error of the mean
Value: 11.7
Estimation Comments A positive (negative) value would suggest AZI values would tend to be larger (smaller) than EZ values.
2.Primary Outcome
Title Gastroparesis Cardinal Symptom Index (GCSI) Score
Hide Description

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.

Time Frame Weeks 4 and 11 (end of periods)
Hide Outcome Measure Data
Hide Analysis Population Description
One subject did not complete this part of analysis.
Arm/Group Title Erythromycin First Then Azithromycin Azithromycin Then Erythromycin
Hide Arm/Group Description:
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 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).
Overall Number of Participants Analyzed 10 9
Mean (Standard Deviation)
Unit of Measure: units on a scale
-1.6  (5.2) -2.9  (7.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Erythromycin First Then Azithromycin, Azithromycin Then Erythromycin
Comments Study planned to accrue 50 subjects, but due to difficult recruitment was not able to meet its objective.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.65
Comments [Not Specified]
Method t-test, 2 sided
Comments Satterthwaite Correction used
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.3
Confidence Interval 95%
-4.8 to 7.5
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.8
Estimation Comments A positive (negative) value would suggest AZI values would tend to be larger (smaller) than EZ values.
3.Secondary Outcome
Title NDI Score
Hide Description

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.

Time Frame Weeks 4 and 11 (end of periods)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Erythromycin First Then Azithromycin Azithromycin Then Erythromycin
Hide Arm/Group Description:
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 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).
Overall Number of Participants Analyzed 10 10
Median (Standard Deviation)
Unit of Measure: units on a scale
1.65  (5.6) 1.30  (4.60)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Erythromycin First Then Azithromycin, Azithromycin Then Erythromycin
Comments Half of the period 2 minus period 1 differences were used, since the difference between these two derived means is an unbiased estimate of the effect size.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.88
Comments [Not Specified]
Method t-test, 2 sided
Comments Satterthwaite correction for unequal standard deviations was used
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 0.35
Confidence Interval (2-Sided) 95%
-4.58 to 5.19
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.30
Estimation Comments A positive (negative) value would suggest AZI values would tend to be larger (smaller) than EZ values.
4.Secondary Outcome
Title TLAG (Time From Ingestion of Meal to Start of Gastric Emptying)
Hide Description 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.
Time Frame Weeks 4 and 11 (end of periods)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Erythromycin First Then Azithromycin Azithromycin Then Erythromycin
Hide Arm/Group Description:
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 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).
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: Minutes
-1.71  (16.2) -0.22  (8.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Erythromycin First Then Azithromycin, Azithromycin Then Erythromycin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.80
Comments [Not Specified]
Method t-test, 2 sided
Comments Satterthwaite Corrected t-test
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.49
Confidence Interval (2-Sided) 95%
-13.9 to 10.9
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.7
Estimation Comments A positive (negative) value would suggest AZI values would tend to be larger (smaller) than EZ values.
5.Secondary Outcome
Title Change in Time to 50% Gastric Emptying: Post Test Less Baseline Pooled Over Orderings
Hide Description 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.
Time Frame Baseline and end of treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Erythromycin
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: Minutes
-11.8  (40.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Erythromycin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.21
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -11.8
Confidence Interval (2-Sided) 95%
-30.9 to 7.3
Parameter Dispersion
Type: Standard Error of the mean
Value: 9.1
Estimation Comments Negative values suggest shorter emptying time post-treatment.
6.Secondary Outcome
Title Change in Time to 50% Emptying: Post Test Less Baseline Pooled Over Orderings
Hide Description 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.
Time Frame at baseline before initiation of the treatment and after completion of each treatment period.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Azithromycin
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 22
Mean (Standard Deviation)
Unit of Measure: minutes
-15.0  (31.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azithromycin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.034
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -15.0
Confidence Interval (2-Sided) 95%
-28.7 to -1.26
Parameter Dispersion
Type: Standard Error of the mean
Value: 6.61
Estimation Comments Negative values suggest shorter emptying time post-treatment.
7.Secondary Outcome
Title Gastroparesis Cardinal Symptom Index (GCSI) Score Change From Baseline to Post Treatment
Hide Description

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.

Time Frame Baseline and end of treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
One subject did not complete this part of analysis.
Arm/Group Title Erythromycin
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 19
Mean (Standard Deviation)
Unit of Measure: units on a scale
-5.32  (8.64)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Erythromycin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.015
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -5.32
Confidence Interval (2-Sided) 95%
-9.48 to -1.16
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.98
Estimation Comments Lower scores are favorable.
8.Secondary Outcome
Title Does GCSI Score Improve (Lower) on Treatment, Pooling the AZ Patients Over Their Treatment Periods? Endpoint is Difference in Post-test Less Baseline
Hide Description

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.

This is a calculation taken with GCSI score at end of treatment minus baseline. Negative value reflects this change.

Time Frame Baseline and end of treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Azithromycin
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 22
Median (Standard Deviation)
Unit of Measure: units on a scale
-6.40  (10.30)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azithromycin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0083
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -6.40
Confidence Interval (2-Sided) 95%
-10.97 to -1.83
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.20
Estimation Comments Lower scores are favorable.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Erythromycin Azithromycin
Hide Arm/Group Description

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.

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.
All-Cause Mortality
Erythromycin Azithromycin
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Erythromycin Azithromycin
Affected / at Risk (%) Affected / at Risk (%)
Total   0/26 (0.00%)   0/26 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Erythromycin Azithromycin
Affected / at Risk (%) Affected / at Risk (%)
Total   1/26 (3.85%)   3/26 (11.54%) 
Gastrointestinal disorders     
abdominal pain  1 [1]  1/26 (3.85%)  3/26 (11.54%) 
nausea  1  0/26 (0.00%)  3/26 (11.54%) 
vomiting  1  0/26 (0.00%)  2/26 (7.69%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (10.1)
[1]
Worsening of pain while on the medication
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Baharak Moshiree MD
Organization: University of Florida
Phone: 305-243-2515
EMail: bmoshiree@med.miami.edu
Publications:
Lee JS, Camilleri M, Zinsmeister A, et al. Accurate simple measurement of gastric emptying by 13C octanoic acid breath test (OBT) in diabetes. Gastroenterology 1999; 116: G4207.
Ware JE Jr, Snow KK, Kosinski M, Gandek B. SF-36 Health Survey: Manual and Interpretation Guide. Boston, MA: The Health Institute, New England Medical Center, 1993.
Layout table for additonal information
Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT01323582     History of Changes
Other Study ID Numbers: 645-2008
First Submitted: March 24, 2011
First Posted: March 25, 2011
Results First Submitted: May 9, 2014
Results First Posted: December 5, 2014
Last Update Posted: December 5, 2014