Efficacy Study of Azithromycin-based Therapy for Bronchiolitis Obliterans

Sponsor

Asan Medical Center (Other)

Overall Status

Terminated

CT.gov ID

NCT01327625

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

[Study Objectives]

To evaluate the efficacy of azithromycin, N-acetylcystein, and inhaled corticosteroid combination therapy in patients with bronchiolitis obliterans as a complication of allogeneic hematopoietic cell transplantation in terms of response rate at 6 months after treatment initiation based on the improvement of FEV1.

Condition or Disease	Intervention/Treatment	Phase
Graft vs Host Disease Bronchiolitis Obliterans	Drug: azithromycin + N-acetylcystein + inhaled corticosteroid	N/A

Detailed Description

Bronchiolitis obliterans (BO) is a graft-versus-host disease of respiratory organs.
Prognosis of BO is very poor, and the overall outcome of patients who are involved in BO is very dismal.
The mechanism of BO has been known to be associated with immune / non-immune response.
Corticosteroid and immunosuppressants are recommended as a best current treatment options for BO, which have been not satisfactory.
Many treatment options have been tried to improve the outcome of BO.
Azithromycin, as an immune modulating agent, has been tried for the treatment of BO, and has been reported to show hopeful results.
N-acetylcystein, as an antioxidative agent, has been tried for BO.
Inhaled corticosteroid may help to improve airway inflammation and decrease the amount of systemic corticosteroid.
These 3 drugs are widely used for other respiratory disease, have been proven to be safe, and have shown some efficacy for BO in various depth of evidence.
In these rationale, we'd like to try the 3-drug combination for BO, to assess the efficacy and safety of these drug combination.

Study Design

Study Type:

Interventional

Actual Enrollment :

6 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Pilot Study Evaluating the Efficacy of Azithromycin, N-acetylcystein and Inhaled Corticosteroid Combination Therapy for Bronchiolitis Obliterans After Allogeneic Hematopoietic Cell Transpantation

Study Start Date :

Mar 1, 2011

Actual Primary Completion Date :

Jun 1, 2013

Actual Study Completion Date :

Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Azithromycin Patient who are diagnosed as bronchiolitis obliterans according to the WHO criteria	Drug: azithromycin + N-acetylcystein + inhaled corticosteroid Azithromycin 500mg qd x 1 week --> 250mg qod x 6 months N-acetylcystein 200mg tid x 6 months Fluticasone 250mcg puff x2/day x 6 months Other Names: Zithromax

Arm

Intervention/Treatment

Experimental: Azithromycin

Patient who are diagnosed as bronchiolitis obliterans according to the WHO criteria

Drug: azithromycin + N-acetylcystein + inhaled corticosteroid

Azithromycin 500mg qd x 1 week --> 250mg qod x 6 months N-acetylcystein 200mg tid x 6 months Fluticasone 250mcg puff x2/day x 6 months

Other Names:

Zithromax

Outcome Measures

Primary Outcome Measures

Response rate based on the improvement of FEV1 [6 months]
Response rate at 6 months after treatment initiation based on the improvement of FEV1

Secondary Outcome Measures

Clinical benefit rate based on the degree of change in FEV1 [6 months]
Clinical benefit rate at 6 months after treatment initiation based on the degree of change in FEV1
change in FEV1 compared with pretreatment level [6 months after treatment initiation]
Change in FEV1 at 6 months after treatment initiation compared with pretreatment level
Reduction rate in immunosuppressive agent / systemic corticosteroid [6 months after treatment initiation]
Reduction rate in immunosuppressive agent / systemic corticosteroid at 6 months after treatment initiation
Discontinuation rate in immunosuppressive agent / systemic corticosteroid [6 months after treatment initiation]
Discontinuation rate in immunosuppressive agent / systemic corticosteroid at 6 months after treatment initiation
Change in dose-intensity of immunosuppressive agent / systemic corticosteroid compared with pretreatment dose-intensity [6 months after treatment initiation]
Change in dose-intensity of immunosuppressive agent / systemic corticosteroid at 6 month after treatment initiation compared with pretreatment dose-intensity
event-free survival [1 year]
overall survival [1year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

15 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients who previously received allogeneic hematopoietic cell transplantation due to hematologic malignancy, bone marrow failure syndrome, and other compatible disease.
Patients who are diagnosed as bronchiolitis obliterans (BO) according to the NIH diagnostic guideline which is suggested as below.
Patients should be 15 years of age or older, but younger than 75 years.
Patients should have estimated life expectancy of more than 3 months.
Patients must have adequate hepatic function (bilirubin less than 3.0 ㎎/㎗, AST and ALT less than three times the upper normal limit).
Patients must have adequate renal function (creatinine less than 2.0 ㎎/㎗).

Exclusion Criteria:

Presence of significant active infection
Presence of uncontrolled bleeding
Any coexisting major illness or organ failure
Patients with a psychiatric disorder or mental deficiency severe as to make compliance with the treatment unlike, and making informed consent impossible.
Nursing women, pregnant women, women of childbearing potential who do not want adequate contraception
Patients with a diagnosis of prior malignancy unless disease-free for at least 5 years following therapy with curative intent (except curatively treated nonmelanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia)