Clarithromycin Modified Release Observational Study for Evaluation of Treatment, Tolerability & Recovery Time in Saudi & Egyptian Clinical Settings (CLOSER)

• Sponsor: Abbott (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01075204
• Collaborator: Eilaf (Other)
• Enrollment: 335
• Locations: 12
• Duration (Months): 12
• Patients Per Site: 27.9
• Patients Per Site Per Month: 2.3

Study Details

Study Description

Brief Summary

The objective is to describe the time to recovery of symptoms (cough, mucus, fever, sore throat, and others), tolerability and compliance of treatment with clarithromycin once daily in patients with upper or lower respiratory tract infections in the routine clinical practice.

Condition or Disease	Intervention/Treatment	Phase
Respiratory Tract Infection	Drug: clarithromycin modified release 500 mg

Study Design

• Study Type: Observational
• Actual Enrollment: 335 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Clarithromycin Modified Release Observational Study for Evaluation of Treatment, Tolerability & Recovery Time in Saudi & Egyptian Clinical Settings (CLOSER)
• Study Start Date: Jan 1, 2011
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Clarithromycin modified release Patients with upper or lower respiratory tract infection were administered clarithromycin modified release 500 mg once daily for 7 days and then followed for a further 3 days, per routine clinical practice.	Drug: clarithromycin modified release 500 mg; clarithromycin modified release 500 mg for 7 days; Other Names: Clarithromycin Modified Release 500 mg (Klacid XL)

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With a Fast Recovery [Day 1 to Day 5]

   Fast recovery is defined as the resolution of symptoms within 5 days or less from the start of clarithromycin modified release treatment. Recovery is defined as returning to the symptom status prior to the onset of the respiratory tract infection, based on the participant and physician's assessment. Data are reported for all symptoms taken together (all symptoms resolved within 5 days) and for each individual symptom.

2. Percentage of Participants With Clinical Success [10 days]

   Clinical success is defined as the disappearance of cough and other symptoms within 10 days or less from the start of clarithromycin treatment.

3. Classification of Overall Response [10 days]

   Based on the participant and physician's assessment, overall symptom response was classified as follows: Fast Responders: participants showing clinical recovery of all symptoms within the first 5 days of treatment. Slow Responders: participants showing clinical recovery between Day 6 & Day 10 (includes participants with a fast response for some symptoms and slow response for the remaining symptoms). Failure response: participants showing no clinical success by Day 10, or showing need for another anti-infective treatment to resolve aggravated symptoms (includes participants with a failure response for some symptoms and either a slow or fast response for the remaining symptoms).

Secondary Outcome Measures

1. Percentage of Participants With Treatment Failure [10 days]

   Treatment failure is defined as failure to return to baseline symptom status (symptom status prior to the onset of the respiratory tract infection) within 10 days or the need for new treatments or medications during the first 10 days for persistence or aggravation of symptoms. Participants with treatment failure were further categorized as: All symptoms improved but not resolved within the study period; Some symptoms improved and some resolved; Some symptoms resolved or improved while other symptoms did not improve (unchanged); Some symptoms resolved or improved while other symptoms became worse.

2. Factors Affecting the Speed of Recovery [10 days]

   Factors affecting the speed of recovery were examined and tested for association with the speed of recovery. Logistic regression was conducted to assess whether the following nine variables; age, gender, body mass index (BMI), concomitant tobacco use, steroid use, bronchial asthma, allergic rhinitis, nasal septum deviation and chronic obstructive pulmonary disease (COPD) act as predictors for speed of recovery of respiratory tract infections. Data shown are the beta regression coefficients for each variable.

3. Number of Participants With Adverse Events [10 days]

   An adverse event (AE) is defined as any untoward medical occurrence in a patient, which does not necessarily have a causal relationship with their treatment. If an adverse event meets any of the following criteria, it is considered a serious adverse event (SAE): Results in death or is life-threatening, results in admission or prolongation of hospitalization, is a congenital anomaly or persistent or significant disability/incapacity or is an important medical event requiring medical or surgical intervention to prevent any of the outcomes listed above. Please see Adverse Events section below for more details.

4. Fever Status at End of Study [10 days]

   Participants with fever (temperature over 37.0 degree of Celsius) at any time during the study were classified at the end of study as resolved, improved or no change. 'No fever' indicates participants with no fever during the study period.

5. Cough Status at End of Study [10 days]

   Participants with cough at any time during the study were classified at the end of study as resolved, improved, became worse, or no change. 'No cough' indicates participants with no cough symptoms during the study period.

6. Sputum Status at End of Study [10 days]

   Participants with sputum symptoms at any time during the study were classified at the end of study as resolved, improved, became worse, or no change. 'No sputum' indicates participants with no sputum symptoms during the study period.

7. Dyspnea Status at End of Study [10 days]

   Participants with dyspnea (shortness of breath) at any time during the study were classified at the end of study as resolved, improved, became worse, or no change. 'No dyspnea' indicates participants with no dyspnea symptoms during the study period.

8. Abnormal Breathing Sounds Status at End of Study [10 days]

   Participants with abnormal breathing sounds such as wheezing or rales at any time during the study were classified at the end of study as resolved, improved, or no change. 'No abnormal breath sounds' indicates participants with no abnormal breathing sounds during the study period.

9. Rhinorrhea Status at End of Study [10 days]

   Participants with rhinorrhea (runny nose) at any time during the study were classified at the end of study as resolved, or no change. 'No rhinorrhea' indicates participants with no rhinorrhea during the study period.

10. Post-nasal Discharge Status at End of Study [10 days]

    Participants with post-nasal discharge at any time during the study were classified at the end of study as resolved, improved, or no change. 'No post-nasal discharge' indicates participants with no post-nasal discharge symptoms during the study period.

11. Percentage of Participants Compliant With Treatment [10 days]

    Treatment compliance was assessed by the study physician at each study visit. The percentage of participants who were compliant with study treatment for 6 days, 7 days and 8 days is reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adults, equal to or more than 18 years years of age

• Patients with respiratory tract infections, including any of the following:

• Acute tracheitis, acute tracheobronchitis

• Acute sinusitis

• Chronic sinusitis

• Acute tonsillopharyngitis

• Acute bronchitis

• Mild community-acquired pneumonia

• Acute exacerbation of chronic bronchitis

Exclusion Criteria:

• Known hypersensitivity to or previously intolerant of macrolides.

• Illness severe enough to warrant hospitalization or parenteral therapy.

• Concomitant use of any of the following medications:

• Drugs metabolized by CYP3A isozyme: alprazolam, astemizole, carbamazepine, cilostazol, cisapride, cyclosporin, disopyramide, ergot alkaloids, lovastatin, methylprednisolone, midazolam, omeprazole, oral anticoagulants (e.g. warfarin), pimozide, quinidine, rifabutin, sildenafil, simvastatin, tacrolimus, terfenadine, triazolam and vinblastine.

• Drugs metabolized by other isozymes within CYP450 system: phenytoin, theophylline and valproate.

• Colchicine, Digoxin, Some antiretrovirals: zidovudine and ritonavir.

• Severe immunodeficiency and chronic disease conditions.

• Renal or hepatic impairment (creatinine clearance under 30 mL/min, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) equal or more than 3x higher level in comparison with the norm).

• Mental condition rendering the subject unable to understand the nature of the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site Ref # / Investigator 50162	Cairo		Egypt
2	Site Ref # / Investigator 50215	Cairo		Egypt
3	Site Ref # / Investigator 50225	Cairo		Egypt
4	Site Ref # / Investigator 50235	Cairo		Egypt
5	Site Ref # / Investigator 50236	Cairo		Egypt
6	Site Ref # / Investigator 50237	Cairo		Egypt
7	Site Ref # / Investigator 51204	Cairo		Egypt
8	Site Ref # / Investigator 51205	Cairo		Egypt
9	Site Ref # / Investigator 50213	Helwan		Egypt
10	Site Ref # / Investigator 51206	Tanta		Egypt
11	Site Ref # / Investigator 51207	Tanta		Egypt
12	Site Ref # / Investigator 22543	Jeddah		Saudi Arabia	21461

Sponsors and Collaborators

• Abbott
• Eilaf

Investigators

• Study Director: Mohamed Tahoun, Bachelor, Abbott Laboratories - Saudi Arabia

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Abbott
• ClinicalTrials.gov Identifier: NCT01075204
• Other Study ID Numbers: P11-989
• First Posted: Feb 25, 2010
• Last Update Posted: Feb 12, 2013
• Last Verified: Feb 1, 2013

• Keywords provided by Abbott: Respiratory Tract Infection; Clarithromycin; Recovery
• Additional relevant MeSH terms: Respiratory Tract Infections; Clarithromycin

Study Results

Participant Flow

Arm/Group Title	Clarithromycin Modified Release
Arm/Group Description	Participants with upper or lower respiratory tract infection were administered clarithromycin modified release 500 mg once daily for 7 days and then followed for a further 3 days, per routine clinical practice.
Period Title: Overall Study
STARTED	335
COMPLETED	335
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Clarithromycin Modified Release
Arm/Group Description	Participants with upper or lower respiratory tract infection were administered clarithromycin modified release 500 mg once daily for 7 days and then followed for a further 3 days, per routine clinical practice.
Overall Participants	335
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35.48 (12.552)
Sex/Gender, Customized (participants) [Number]
Male	205 61.2%
Female	122 36.4%
Missing	8 2.4%
Region of Enrollment (participants) [Number]
Egypt	120 35.8%
Saudi Arabia	215 64.2%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With a Fast Recovery
Description	Fast recovery is defined as the resolution of symptoms within 5 days or less from the start of clarithromycin modified release treatment. Recovery is defined as returning to the symptom status prior to the onset of the respiratory tract infection, based on the participant and physician's assessment. Data are reported for all symptoms taken together (all symptoms resolved within 5 days) and for each individual symptom.
Time Frame	Day 1 to Day 5

Outcome Measure Data

Analysis Population Description

All enrolled participants. For the individual symptoms, N indicates the number of participants with that symptom at Baseline and with available recovery data.

Arm/Group Title	Clarithromycin Modified Release
Arm/Group Description	Participants with upper or lower respiratory tract infection were administered clarithromycin modified release 500 mg once daily for 7 days and then followed for a further 3 days, per routine clinical practice.
Measure Participants	335
All symptoms together [N=335]	12.8 3.8%
Fever response [N=184]	54.3 16.2%
Cough response [N=215]	27.4 8.2%
Sputum response [N=212]	29.7 8.9%
Dyspnea response [N=62]	37.1 11.1%
Abnormal breath sounds response [N=47]	42.6 12.7%
Rhinorrhea response [N=113]	28.3 8.4%
Nasal congestion response [N=233]	33.5 10%
Post-nasal discharge response [N=178]	18.5 5.5%
Sneezing response [N=87]	25.3 7.6%
Sore throat response [N=200]	38.0 11.3%
Painful swallowing response [N=162]	38.9 11.6%
Itchy watery eye response [N=33]	6.1 1.8%
Malaise response [N=68]	30.9 9.2%
Myalgia response [N=79]	34.2 10.2%

2. Secondary Outcome

Title	Percentage of Participants With Treatment Failure
Description	Treatment failure is defined as failure to return to baseline symptom status (symptom status prior to the onset of the respiratory tract infection) within 10 days or the need for new treatments or medications during the first 10 days for persistence or aggravation of symptoms. Participants with treatment failure were further categorized as: All symptoms improved but not resolved within the study period; Some symptoms improved and some resolved; Some symptoms resolved or improved while other symptoms did not improve (unchanged); Some symptoms resolved or improved while other symptoms became worse.
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

All enrolled patients

Arm/Group Title	Clarithromycin Modified Release
Arm/Group Description	Participants with upper or lower respiratory tract infection were administered clarithromycin modified release 500 mg once daily for 7 days and then followed for a further 3 days, per routine clinical practice.
Measure Participants	335
Treatment failure total	13.1 3.9%
All symptoms improved but not resolved	0.9 0.3%
Some symptoms improved and some resolved	3.9 1.2%
Some symptoms resolved/improved, others unchanged	6.9 2.1%
Some symptoms resolved/improved/others worsened	1.5 0.4%

3. Secondary Outcome

Title	Factors Affecting the Speed of Recovery
Description	Factors affecting the speed of recovery were examined and tested for association with the speed of recovery. Logistic regression was conducted to assess whether the following nine variables; age, gender, body mass index (BMI), concomitant tobacco use, steroid use, bronchial asthma, allergic rhinitis, nasal septum deviation and chronic obstructive pulmonary disease (COPD) act as predictors for speed of recovery of respiratory tract infections. Data shown are the beta regression coefficients for each variable.
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

All enrolled patients

Arm/Group Title	Clarithromycin Modified Release
Arm/Group Description	Participants with upper or lower respiratory tract infection were administered clarithromycin modified release 500 mg once daily for 7 days and then followed for a further 3 days, per routine clinical practice.
Measure Participants	335
Age	-0.007
Gender	0.216
Body mass index (BMI)	0.004
Tobacco use	0.419
Steroid use	-0.456
Bronchial asthma	0.140
Allergic rhinitis	19.292
Nasal septum deviation	18.698
Chronic obstructive pulmonary disease (COPD)	19.281

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Clarithromycin Modified Release
	Comments	Logistic regression: Omnibus Test of Model Coefficients (all the nine variables are considered together).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.334
	Comments
	Method	Chi-squared
	Comments	9 degrees of freedom.

4. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	An adverse event (AE) is defined as any untoward medical occurrence in a patient, which does not necessarily have a causal relationship with their treatment. If an adverse event meets any of the following criteria, it is considered a serious adverse event (SAE): Results in death or is life-threatening, results in admission or prolongation of hospitalization, is a congenital anomaly or persistent or significant disability/incapacity or is an important medical event requiring medical or surgical intervention to prevent any of the outcomes listed above. Please see Adverse Events section below for more details.
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

All enrolled patients.

Arm/Group Title	Clarithromycin Modified Release
Arm/Group Description	Participants with upper or lower respiratory tract infection were administered clarithromycin modified release 500 mg once daily for 7 days and then followed for a further 3 days, per routine clinical practice.
Measure Participants	335
Any adverse event	2 0.6%
Serious adverse event	0 0%

5. Primary Outcome

Title	Percentage of Participants With Clinical Success
Description	Clinical success is defined as the disappearance of cough and other symptoms within 10 days or less from the start of clarithromycin treatment.
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

All enrolled patients.

Arm/Group Title	Clarithromycin Modified Release
Arm/Group Description	Participants with upper or lower respiratory tract infection were administered clarithromycin modified release 500 mg once daily for 7 days and then followed for a further 3 days, per routine clinical practice.
Measure Participants	335
Number (95% Confidence Interval) [percentage of participants]	86.9 25.9%

6. Primary Outcome

Title	Classification of Overall Response
Description	Based on the participant and physician's assessment, overall symptom response was classified as follows: Fast Responders: participants showing clinical recovery of all symptoms within the first 5 days of treatment. Slow Responders: participants showing clinical recovery between Day 6 & Day 10 (includes participants with a fast response for some symptoms and slow response for the remaining symptoms). Failure response: participants showing no clinical success by Day 10, or showing need for another anti-infective treatment to resolve aggravated symptoms (includes participants with a failure response for some symptoms and either a slow or fast response for the remaining symptoms).
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

All enrolled patients

Arm/Group Title	Clarithromycin Modified Release
Arm/Group Description	Participants with upper or lower respiratory tract infection were administered clarithromycin modified release 500 mg once daily for 7 days and then followed for a further 3 days, per routine clinical practice.
Measure Participants	335
Fast responders	43 12.8%
Slow responders	248 74%
Failure response	44 13.1%

7. Secondary Outcome

Title	Fever Status at End of Study
Description	Participants with fever (temperature over 37.0 degree of Celsius) at any time during the study were classified at the end of study as resolved, improved or no change. 'No fever' indicates participants with no fever during the study period.
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

All enrolled patients

Arm/Group Title	Clarithromycin Modified Release
Arm/Group Description	Participants with upper or lower respiratory tract infection were administered clarithromycin modified release 500 mg once daily for 7 days and then followed for a further 3 days, per routine clinical practice.
Measure Participants	335
Resolved	120 35.8%
Improved	70 20.9%
No change	5 1.5%
No fever	140 41.8%

8. Secondary Outcome

Title	Cough Status at End of Study
Description	Participants with cough at any time during the study were classified at the end of study as resolved, improved, became worse, or no change. 'No cough' indicates participants with no cough symptoms during the study period.
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

Enrolled patients with cough data available.

Arm/Group Title	Clarithromycin Modified Release
Arm/Group Description	Participants with upper or lower respiratory tract infection were administered clarithromycin modified release 500 mg once daily for 7 days and then followed for a further 3 days, per routine clinical practice.
Measure Participants	333
Resolved	93 27.8%
Improved	100 29.9%
No change	23 6.9%
Worsened	4 1.2%
No cough	113 33.7%

9. Secondary Outcome

Title	Sputum Status at End of Study
Description	Participants with sputum symptoms at any time during the study were classified at the end of study as resolved, improved, became worse, or no change. 'No sputum' indicates participants with no sputum symptoms during the study period.
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

Enrolled patients with sputum data available.

Arm/Group Title	Clarithromycin Modified Release
Arm/Group Description	Participants with upper or lower respiratory tract infection were administered clarithromycin modified release 500 mg once daily for 7 days and then followed for a further 3 days, per routine clinical practice.
Measure Participants	333
Resolved	88 26.3%
Improved	102 30.4%
No change	19 5.7%
Worsened	4 1.2%
No sputum	120 35.8%

10. Secondary Outcome

Title	Dyspnea Status at End of Study
Description	Participants with dyspnea (shortness of breath) at any time during the study were classified at the end of study as resolved, improved, became worse, or no change. 'No dyspnea' indicates participants with no dyspnea symptoms during the study period.
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

All enrolled patients

Arm/Group Title	Clarithromycin Modified Release
Arm/Group Description	Participants with upper or lower respiratory tract infection were administered clarithromycin modified release 500 mg once daily for 7 days and then followed for a further 3 days, per routine clinical practice.
Measure Participants	335
Resolved	31 9.3%
Improved	28 8.4%
No change	2 0.6%
Worsened	1 0.3%
No dyspnea	273 81.5%

11. Secondary Outcome

Title	Abnormal Breathing Sounds Status at End of Study
Description	Participants with abnormal breathing sounds such as wheezing or rales at any time during the study were classified at the end of study as resolved, improved, or no change. 'No abnormal breath sounds' indicates participants with no abnormal breathing sounds during the study period.
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

All enrolled patients

Arm/Group Title	Clarithromycin Modified Release
Arm/Group Description	Participants with upper or lower respiratory tract infection were administered clarithromycin modified release 500 mg once daily for 7 days and then followed for a further 3 days, per routine clinical practice.
Measure Participants	335
Resolved	30 9%
Improved	13 3.9%
No change	4 1.2%
No abnormal breath sounds	288 86%

12. Secondary Outcome

Title	Rhinorrhea Status at End of Study
Description	Participants with rhinorrhea (runny nose) at any time during the study were classified at the end of study as resolved, or no change. 'No rhinorrhea' indicates participants with no rhinorrhea during the study period.
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

All enrolled patients

Arm/Group Title	Clarithromycin Modified Release
Arm/Group Description	Participants with upper or lower respiratory tract infection were administered clarithromycin modified release 500 mg once daily for 7 days and then followed for a further 3 days, per routine clinical practice.
Measure Participants	335
Resolved	55 16.4%
Improved	56 16.7%
No change	2 0.6%
No rhinorrhea	222 66.3%

13. Secondary Outcome

Title	Post-nasal Discharge Status at End of Study
Description	Participants with post-nasal discharge at any time during the study were classified at the end of study as resolved, improved, or no change. 'No post-nasal discharge' indicates participants with no post-nasal discharge symptoms during the study period.
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

Enrolled patients with post-nasal discharge data available.

Arm/Group Title	Clarithromycin Modified Release
Arm/Group Description	Participants with upper or lower respiratory tract infection were administered clarithromycin modified release 500 mg once daily for 7 days and then followed for a further 3 days, per routine clinical practice.
Measure Participants	333
Resolved	75 22.4%
Improved	98 29.3%
No change	6 1.8%
No post-nasal discharge	154 46%

14. Secondary Outcome

Title	Percentage of Participants Compliant With Treatment
Description	Treatment compliance was assessed by the study physician at each study visit. The percentage of participants who were compliant with study treatment for 6 days, 7 days and 8 days is reported.
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

All enrolled patients.

Arm/Group Title	Clarithromycin Modified Release
Arm/Group Description	Participants with upper or lower respiratory tract infection were administered clarithromycin modified release 500 mg once daily for 7 days and then followed for a further 3 days, per routine clinical practice.
Measure Participants	335
6 days	43 12.8%
7 days	54 16.1%
8 days	3 0.9%

Adverse Events

Time Frame	10 days
Arm/Group Title	Clarithromycin Modified Release
Arm/Group Description	Participants with upper or lower respiratory tract infection were administered clarithromycin modified release 500 mg once daily for 7 days and then followed for a further 3 days, per routine clinical practice.
All Cause Mortality
	Clarithromycin Modified Release
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Clarithromycin Modified Release
	Affected / at Risk (%)	# Events
Total	0/335 (0%)
Other (Not Including Serious) Adverse Events
	Clarithromycin Modified Release
	Affected / at Risk (%)	# Events
Total	2/335 (0.6%)
Gastrointestinal disorders
Dyspepsia	1/335 (0.3%)
Diarrhea	1/335 (0.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Abbott requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. Abbott requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if Abbott needs to secure patent or proprietary protection.