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Efficacy Study of Azithromycin-based Therapy for Bronchiolitis Obliterans

Not Applicable
Terminated
Conditions
Graft vs Host Disease
Bronchiolitis Obliterans
Interventions
Registration Number
NCT01327625
Lead Sponsor
Asan Medical Center
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.

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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
6
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)

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Azithromycinazithromycin + N-acetylcystein + inhaled corticosteroidPatient who are diagnosed as bronchiolitis obliterans according to the WHO criteria
Primary Outcome Measures
NameTimeMethod
Response rate based on the improvement of FEV16 months

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

Secondary Outcome Measures
NameTimeMethod
Clinical benefit rate based on the degree of change in FEV16 months

Clinical benefit rate at 6 months after treatment initiation based on the degree of change in FEV1

change in FEV1 compared with pretreatment level6 months after treatment initiation

Change in FEV1 at 6 months after treatment initiation compared with pretreatment level

Reduction rate in immunosuppressive agent / systemic corticosteroid6 months after treatment initiation

Reduction rate in immunosuppressive agent / systemic corticosteroid at 6 months after treatment initiation

Discontinuation rate in immunosuppressive agent / systemic corticosteroid6 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-intensity6 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 survival1 year
overall survival1year

Trial Locations

Locations (1)

Asan Medical Center

🇰🇷

Seoul, Korea, Republic of

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