Efficacy Study of Azithromycin-based Therapy for Bronchiolitis Obliterans

This study has been terminated.
(Preliminary reports of this study was too bad.)
Sponsor:
Information provided by (Responsible Party):
Dae-Young Kim, Asan Medical Center
ClinicalTrials.gov Identifier:
NCT01327625
First received: March 31, 2011
Last updated: July 8, 2014
Last verified: July 2014
  Purpose

[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 Intervention
Graft vs Host Disease
Bronchiolitis Obliterans
Drug: azithromycin + N-acetylcystein + inhaled corticosteroid

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Asan Medical Center:

Primary Outcome Measures:
  • Response rate based on the improvement of FEV1 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Clinical benefit rate at 6 months after treatment initiation based on the degree of change in FEV1

  • change in FEV1 compared with pretreatment level [ Time Frame: 6 months after treatment initiation ] [ Designated as safety issue: No ]
    Change in FEV1 at 6 months after treatment initiation compared with pretreatment level

  • Reduction rate in immunosuppressive agent / systemic corticosteroid [ Time Frame: 6 months after treatment initiation ] [ Designated as safety issue: No ]
    Reduction rate in immunosuppressive agent / systemic corticosteroid at 6 months after treatment initiation

  • Discontinuation rate in immunosuppressive agent / systemic corticosteroid [ Time Frame: 6 months after treatment initiation ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months after treatment initiation ] [ Designated as safety issue: No ]
    Change in dose-intensity of immunosuppressive agent / systemic corticosteroid at 6 month after treatment initiation compared with pretreatment dose-intensity

  • event-free survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • overall survival [ Time Frame: 1year ] [ Designated as safety issue: No ]

Enrollment: 6
Study Start Date: March 2011
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Zithromax

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.
  Eligibility

Ages Eligible for Study:   15 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01327625

Locations
Korea, Republic of
Asan Medical Center
Seoul, Korea, Republic of, 138-736
Sponsors and Collaborators
Asan Medical Center
Investigators
Principal Investigator: Dae-Young Kim, M.D. Asan Medical Center
  More Information

Publications:

Responsible Party: Dae-Young Kim, Assistant Professor, Asan Medical Center
ClinicalTrials.gov Identifier: NCT01327625     History of Changes
Other Study ID Numbers: AMC-ALLO-041
Study First Received: March 31, 2011
Last Updated: July 8, 2014
Health Authority: South Korea: Korea Food and Drug Administration (KFDA)

Keywords provided by Asan Medical Center:
Allogeneic hematopoietic cell transplantation
Graft versus host disease
Bronchiolitis obliterans
Azithromycin
N-acetylcystein
Fluticasone
Inhaled steroid

Additional relevant MeSH terms:
Bronchiolitis
Bronchiolitis Obliterans
Graft vs Host Disease
Bronchitis
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Tract Infections
Immune System Diseases
Azithromycin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014