Oral Azithromycin Versus Doxycycline in Posterior Blepharitis

• Sponsor: Tehran University of Medical Sciences (Other)
• Overall Status: Completed
• CT.gov ID: NCT01783860
• Collaborator: (none)
• Enrollment: 100
• Location: 1
• Arms: 2
• Duration (Months): 5.9
• Patients Per Site Per Month: 16.8

Study Details

Study Description

Brief Summary

One hundred patients with the diagnosis of posterior blepharitis based on history taking and proper physical examinations by two experienced ophthalmologists will include in the study.

Patients will diagnose with posterior blepharitis if they score at least one in two symptoms (based on a subjective grading scale) and two signs (based on an objective grading scale) of posterior blepharitis according to study criteria. Patients will exclude if they have the following criteria: age< 12 years old,history of previous ocular or lacrimal surgery,previous usage of contact lenses,any history of ocular allergy,history of systemic diseases with ocular involvement (except rosacea), history of usage of topical or systemic antibiotic in the last month, pregnancy or lactating mothers, liver failure and any history of sensitivity to cyclines.

Qualified patients then randomly receive oral azithromycin (2 of 250 mg capsules for the first day and 250mg for the next 4 days) or oral doxycycline (100mg capsule every 12 hours for one month) in a double-blinded fashion. each patients in both treatment groups will accurately instruct to apply warm compress and eyelid scrubbing 2 times a day for 5 minutes each in the treatment period. Symptoms and signs were recorded for each patient in two treatment groups at baseline visit (before treatment) and then in the days 7, 31, 37 and 61 after treatment.

Condition or Disease	Intervention/Treatment	Phase
Posterior Blepharitis	Drug: Azithromycin; Drug: Doxycycline	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Treatment
• Official Title: Study of the Effect of Oral Azithromycin on Posterior Blepharitis
• Study Start Date: Jan 1, 2013
• Actual Primary Completion Date: Jul 1, 2013
• Actual Study Completion Date: Jul 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Oral Azithromycin Two 250 mg capsules (500 mg) of Azithromycin for the first day and 250mg/day for the next 4 days.	Drug: Azithromycin; Other Names: Azithromycin (Razak Co., Tehran)
Active Comparator: Doxycycline Oral doxycycline 100mg capsule every 12 hours for one month	Drug: Doxycycline; Other Names: Doxycycline (Kimidarou Co., Tehran)

Outcome Measures

Primary Outcome Measures

1. Change of Blepharitis Symptoms Score [Change from the baseline until 61 days after treatment]

   Five main ocular symptoms of posterior blepharitis (itching, foreign body sensation, dryness, burning, and lid swelling) will be asked of each patient and graded at baseline, and days 7, 31, 37 and 61 after treatment. For each item there was a question with scale from zero to three (zero for no symptom three for maximum symptom). Therefore, maximum score for symptoms was 15 (worse outcome) and minimum score for symptoms was zero (better outcome). Finally, we reported a change in total score calculated as the latest time point (61 days) minus the earliest time point.

2. Change of Symptoms and Signs Scores (Difference Between Total Score of First Time and 61 Days Later), Total Severity Score [zero time and 61 days later]

   Total severity score was a combined score of symptoms and signs. For symptoms, there were five items and for signs there were seven items. Each items had three scales form Zero (no symptom) to three (severe symptom). Therefore, there was 12 items to calculate total severity score. Maximum score was 36 (worse outcome) and minimum score was zero (better outcome). A change in total severity score calculated as the latest time period (61 days) minus earliest time point.

Secondary Outcome Measures

1. Main Ocular Signs [Change from baseline until 61 days after treatment]

   lid margin debris, lid margin redness, Meibomian gland (MG) secretion, occluded MG, conjunctival redness, tear brake up time and ocular surface staining at Baseline, and days 7, 31, 37 and 61 after treatment were measured. For each items there was a question with scale form zero to three (zero for no sign to three for maximum sign). Therefore, maximum score for signs was 21 (worse outcome) and minimum score was zero (better outcome). We calculated a total score for signs. Finally, we reported a change in total score calculated as the latest time point (61 days) minus earliest time point.

Other Outcome Measures

1. Change of Total Severity Score Between Baseline and 7 Days Later [baseline and 7 days later]

   Total severity score was a combined score of symptoms and signs. For symptoms, there were five items and for signs there were seven items. Each items had three scales form Zero (no symptom) to three (severe symptom). Therefore, there was 12 items to calculate total severity score. Maximum score was 36 (worse outcome) and minimum score was zero (better outcome). A change in total severity score calculated as the latest time period (7 days) minus earliest time point.

2. Change of Total Severity Score Between Baseline and 31 Days Later [baseline and 31 days later]

   Total severity score was a combined score of symptoms and signs. For symptoms, there were five items and for signs there were seven items. Each items had three scales form Zero (no symptom) to three (severe symptom). Therefore, there was 12 items to calculate total severity score. Maximum score was 36 (worse outcome) and minimum score was zero (better outcome). A change in total severity score calculated as the latest time period (31 days) minus earliest time point.

3. Change of Total Severity Score Between Baseline and 37 Days Later [baseline and 37 days later]

   Total severity score was a combined score of symptoms and signs. For symptoms, there were five items and for signs there were seven items. Each items had three scales form Zero (no symptom) to three (severe symptom). Therefore, there was 12 items to calculate total severity score. Maximum score was 36 (worse outcome) and minimum score was zero (better outcome). A change in total severity score calculated as the latest time period (37 days) minus earliest time point.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 13 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Patients were diagnosed with posterior blepharitis if they scored at least one in two symptoms (based on a subjective grading scale) and two signs (based on an objective grading scale) of posterior blepharitis according to study criteria

Exclusion Criteria:

Patients were excluded if they had the following criteria: age< 12 years old,history of previous ocular or lacrimal surgery,previous usage of contact lenses,any history of ocular allergy,history of systemic diseases with ocular involvement (except rosacea), history of usage of topical or systemic antibiotic in the last month, pregnancy or lactating mothers, liver failure and any history of sensitivity to cyclines

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rassoul Akram Hospital	Tehran		Iran, Islamic Republic of	14455-364

Sponsors and Collaborators

• Tehran University of Medical Sciences

Investigators

• Study Director: Mohsen B Kashkouli, MD, Tehran University of Medical Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Tehran University of Medical Sciences
• ClinicalTrials.gov Identifier: NCT01783860
• Other Study ID Numbers: 90-01-124-13076
• First Posted: Feb 5, 2013
• Last Update Posted: Feb 12, 2014
• Last Verified: Dec 1, 2013

• Keywords provided by Tehran University of Medical Sciences: Azithromycin; Doxycycline; Posterior Blepharitis
• Additional relevant MeSH terms: Blepharitis; Meibomian Gland Dysfunction; Azithromycin; Doxycycline

Study Results

Participant Flow

Recruitment Details	All 100 patients were selected from the eye clinic of Rasoule-Akram hospital during the study period. The patients were recruited sequentially.
Pre-assignment Detail	Patients were excluded if they had: age< 12 years,history of ocular or lacrimal surgery,previous usage of contact lenses,history of ocular allergy or systemic diseases with ocular involvement, history of usage of topical or systemic antibiotic in the last month, pregnant or lactating mothers, liver failure and history of sensitivity to Cyclines.

Arm/Group Title	Doxycycline	Oral Azithromycin
Arm/Group Description	Oral doxycycline 100mg capsule every 12 hours for one month Doxycycline :	Two 250 mg capsules (500 mg) of Azithromycin for the first day and 250mg/day for the next 4 days. Azithromycin :
Period Title: Overall Study
STARTED	50	50
COMPLETED	50	50
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Doxycycline	Oral Azithromycin	Total
Arm/Group Description	Oral doxycycline 100mg capsule every 12 hours for one month Doxycycline :	Two 250 mg capsules (500 mg) of Azithromycin for the first day and 250mg/day for the next 4 days. Azithromycin :	Total of all reporting groups
Overall Participants	50	50	100
Age (Count of Participants)
<=18 years	2 4%	4 8%	6 6%
Between 18 and 65 years	46 92%	43 86%	89 89%
>=65 years	2 4%	3 6%	5 5%
Sex: Female, Male (Count of Participants)
Female	24 48%	26 52%	50 50%
Male	26 52%	24 48%	50 50%
Region of Enrollment (participants) [Number]
Iran, Islamic Republic of	50 100%	50 100%	100 100%

Outcome Measures

1. Primary Outcome

Title	Change of Blepharitis Symptoms Score
Description	Five main ocular symptoms of posterior blepharitis (itching, foreign body sensation, dryness, burning, and lid swelling) will be asked of each patient and graded at baseline, and days 7, 31, 37 and 61 after treatment. For each item there was a question with scale from zero to three (zero for no symptom three for maximum symptom). Therefore, maximum score for symptoms was 15 (worse outcome) and minimum score for symptoms was zero (better outcome). Finally, we reported a change in total score calculated as the latest time point (61 days) minus the earliest time point.
Time Frame	Change from the baseline until 61 days after treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Doxycycline	Oral Azithromycin
Arm/Group Description	Oral doxycycline 100mg capsule every 12 hours for one month Doxycycline :	Two 250 mg capsules (500 mg) of Azithromycin for the first day and 250mg/day for the next 4 days. Azithromycin :
Measure Participants	50	50
Mean (Standard Deviation) [score]	1.8 (2.5)	2.8 (2.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Doxycycline, Oral Azithromycin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments
	Method	t-test, 1 sided
	Comments

2. Secondary Outcome

Title	Main Ocular Signs
Description	lid margin debris, lid margin redness, Meibomian gland (MG) secretion, occluded MG, conjunctival redness, tear brake up time and ocular surface staining at Baseline, and days 7, 31, 37 and 61 after treatment were measured. For each items there was a question with scale form zero to three (zero for no sign to three for maximum sign). Therefore, maximum score for signs was 21 (worse outcome) and minimum score was zero (better outcome). We calculated a total score for signs. Finally, we reported a change in total score calculated as the latest time point (61 days) minus earliest time point.
Time Frame	Change from baseline until 61 days after treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Doxycycline	Oral Azithromycin
Arm/Group Description	Oral doxycycline 100mg capsule every 12 hours for one month Doxycycline :	Two 250 mg capsules (500 mg) of Azithromycin for the first day and 250mg/day for the next 4 days. Azithromycin :
Measure Participants	50	50
Mean (Standard Deviation) [units on a scale]	4.7 (2.3)	5.7 (2.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Doxycycline, Oral Azithromycin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.01
	Comments
	Method	t-test, 1 sided
	Comments

3. Primary Outcome

Title	Change of Symptoms and Signs Scores (Difference Between Total Score of First Time and 61 Days Later), Total Severity Score
Description	Total severity score was a combined score of symptoms and signs. For symptoms, there were five items and for signs there were seven items. Each items had three scales form Zero (no symptom) to three (severe symptom). Therefore, there was 12 items to calculate total severity score. Maximum score was 36 (worse outcome) and minimum score was zero (better outcome). A change in total severity score calculated as the latest time period (61 days) minus earliest time point.
Time Frame	zero time and 61 days later

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Doxycycline	Oral Azithromycin
Arm/Group Description	Oral doxycycline 100mg capsule every 12 hours for one month Doxycycline :	Two 250 mg capsules (500 mg) of Azithromycin for the first day and 250mg/day for the next 4 days. Azithromycin :
Measure Participants	50	50
Mean (Standard Deviation) [units on a scale]	6.5 (4.1)	8.6 (3.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Doxycycline, Oral Azithromycin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.007
	Comments
	Method	t-test, 1 sided
	Comments

4. Other Pre-specified Outcome

Title	Change of Total Severity Score Between Baseline and 7 Days Later
Description	Total severity score was a combined score of symptoms and signs. For symptoms, there were five items and for signs there were seven items. Each items had three scales form Zero (no symptom) to three (severe symptom). Therefore, there was 12 items to calculate total severity score. Maximum score was 36 (worse outcome) and minimum score was zero (better outcome). A change in total severity score calculated as the latest time period (7 days) minus earliest time point.
Time Frame	baseline and 7 days later

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Doxycycline	Oral Azithromycin
Arm/Group Description	Oral doxycycline 100mg capsule every 12 hours for one month Doxycycline :	Two 250 mg capsules (500 mg) of Azithromycin for the first day and 250mg/day for the next 4 days. Azithromycin :
Measure Participants	50	50
Mean (Standard Deviation) [units on a scale]	3.9 (2.5)	4.3 (2.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Doxycycline, Oral Azithromycin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	> 0.05
	Comments
	Method	t-test, 1 sided
	Comments

5. Other Pre-specified Outcome

Title	Change of Total Severity Score Between Baseline and 31 Days Later
Description	Total severity score was a combined score of symptoms and signs. For symptoms, there were five items and for signs there were seven items. Each items had three scales form Zero (no symptom) to three (severe symptom). Therefore, there was 12 items to calculate total severity score. Maximum score was 36 (worse outcome) and minimum score was zero (better outcome). A change in total severity score calculated as the latest time period (31 days) minus earliest time point.
Time Frame	baseline and 31 days later

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Doxycycline	Oral Azithromycin
Arm/Group Description	Oral doxycycline 100mg capsule every 12 hours for one month Doxycycline :	Two 250 mg capsules (500 mg) of Azithromycin for the first day and 250mg/day for the next 4 days. Azithromycin :
Measure Participants	50	50
Mean (Standard Deviation) [units on a scale]	5.2 (2.4)	6.4 (2.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Doxycycline, Oral Azithromycin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.02
	Comments
	Method	t-test, 1 sided
	Comments

6. Other Pre-specified Outcome

Title	Change of Total Severity Score Between Baseline and 37 Days Later
Description	Total severity score was a combined score of symptoms and signs. For symptoms, there were five items and for signs there were seven items. Each items had three scales form Zero (no symptom) to three (severe symptom). Therefore, there was 12 items to calculate total severity score. Maximum score was 36 (worse outcome) and minimum score was zero (better outcome). A change in total severity score calculated as the latest time period (37 days) minus earliest time point.
Time Frame	baseline and 37 days later

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Doxycycline	Oral Azithromycin
Arm/Group Description	Oral doxycycline 100mg capsule every 12 hours for one month Doxycycline :	Two 250 mg capsules (500 mg) of Azithromycin for the first day and 250mg/day for the next 4 days. Azithromycin :
Measure Participants	50	50
Mean (Standard Deviation) [units on a scale]	6.3 (3.2)	7.4 (3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Doxycycline, Oral Azithromycin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.08
	Comments
	Method	t-test, 1 sided
	Comments

Adverse Events

Arm/Group Title	Doxycycline		Oral Azithromycin
Arm/Group Description	Oral doxycycline 100mg capsule every 12 hours for one month Doxycycline :		Two 250 mg capsules (500 mg) of Azithromycin for the first day and 250mg/day for the next 4 days. Azithromycin :
All Cause Mortality
	Doxycycline		Oral Azithromycin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Doxycycline		Oral Azithromycin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/50 (24%)		3/50 (6%)
Gastrointestinal disorders
vomiting and loss of appetide	12/50 (24%)		3/50 (6%)
Other (Not Including Serious) Adverse Events
	Doxycycline		Oral Azithromycin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/50 (0%)		0/50 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.