Special Investigation of Clarith/Klaricid in Patients With Non-tuberculous Mycobacterial Pulmonary Infections

Sponsor
Mylan Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01097005
Collaborator
Taisho Pharmaceutical Co., Ltd. (Industry)
466
59
61.9
7.9
0.1

Study Details

Study Description

Brief Summary

To evaluate the efficacy and safety of long-term treatment with clarithromycin in patients with Non-tuberculous Mycobacterial Pulmonary Infections.

Condition or Disease Intervention/Treatment Phase

    Detailed Description

    Background: The revised 2007 American Thoracic Society/Infectious Diseases Society of America guidelines recommend a clarithromycin-based combination therapy for treatment of Mycobacterium avium complex (MAC) lung disease and stipulate approximately 1 year of continuous treatment after bacilli negative conversion. However, supporting data are insufficient.

    Objectives: To obtain data on the clinical outcome of clarithromycin-based regimens by conducting a nationwide prospective study mainly of MAC lung disease.

    Methods: In accordance with the guidelines, patients were enrolled in this survey according to their chest radiographic findings and microbiologic test results. They were treated with a multi-drug regimen including clarithromycin, rifampicin, and ethambutol (clarithromycin -based regimen) until bacilli negative conversion on continual treatment for 1 year. Data were collected "pre-administration," "on the bacilli negative conversion," and "at 6 months after the end of treatment."

    Study Design

    Study Type:
    Observational
    Actual Enrollment :
    466 participants
    Observational Model:
    Cohort
    Time Perspective:
    Prospective
    Official Title:
    Special Investigation of Clarith/Klaricid in Patients With Non-tuberculous Mycobacterial Pulmonary Infections
    Study Start Date :
    Jan 1, 2009
    Actual Primary Completion Date :
    Mar 1, 2014
    Actual Study Completion Date :
    Mar 1, 2014

    Arms and Interventions

    Arm Intervention/Treatment
    Klaricid

    Those with an exposure

    Outcome Measures

    Primary Outcome Measures

    1. Bacilli Negative Conversion Rate [During the treatment with clarithromycin, from 40 days to 1232 days]

      Number of participants who tested positive for Bacilli before treatment and converted to Bacilli Negative at any point during the treatment with clarithromycin

    Secondary Outcome Measures

    1. Efficacy Evaluation Using the 4-rank Scale of "Effective", "Ineffective", "Deterioration", or "Impossible" by the Investigator [When treatment with clarithromycin is discontinued, from 40 days to 1232 days]

      Number of participants who evaluated for efficacy of clarithromycin with the 4-rank Scales ("Effective", "Ineffective", "Deterioration", "Impossible")

    2. Bacteriological Relapse Related to Duration of Clarithromycin Administration [36 months]

      Number of patients who have bacteriological relapse related to duration of Clarithromycin (CLR) administration after initial negative conversion

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    15 Years to 99 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    Inclusion Criteria

    • Patients with Pulmonary non-tuberculous mycoplasma infection and who are indicated for treatment with Klaricid

    Exclusion Criteria

    • Contraindications according to the package insert

    • Patients with a history of hypersensitivity to any ingredient of Klaricid

    • Patients who are receiving pimozide, ergot-containing products, or cisapride

    • Patients who have AIDS (Acquired Immune Deficiency Syndrome)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Site Reference ID/Investigator# 36460 Aichi Japan
    2 Site Reference ID/Investigator# 39122 Aichi Japan
    3 Site Reference ID/Investigator# 36463 Akita Japan
    4 Site Reference ID/Investigator# 36470 Ehime Japan
    5 Site Reference ID/Investigator# 36471 Fukuoka-shi Japan
    6 Site Reference ID/Investigator# 36472 Fukuoka Japan
    7 Site Reference ID/Investigator# 36473 Fukushima Japan
    8 Site Reference ID/Investigator# 36474 Gifu Japan
    9 Site Reference ID/Investigator# 36475 Hiroshima Japan
    10 Site Reference ID/Investigator# 36482 Hyogo Japan
    11 Site Reference ID/Investigator# 36465 Inzai Japan
    12 Site Reference ID/Investigator# 36483 Ishikawa Japan
    13 Site Reference ID/Investigator# 36484 Kagoshima Japan
    14 Site Reference ID/Investigator# 36485 Kanagawa Japan
    15 Site Reference ID/Investigator# 36486 Kanagawa Japan
    16 Site Reference ID/Investigator# 36487 Kanagawa Japan
    17 Site Reference ID/Investigator# 54466 Kitakyushu Japan
    18 Site Reference ID/Investigator# 54468 Kobe Japan
    19 Site Reference ID/Investigator# 36488 Kochi Japan
    20 Site Reference ID/Investigator# 36513 Kofu Japan
    21 Site Reference ID/Investigator# 39126 Kumamoto Japan
    22 Site Reference ID/Investigator# 36489 Kyoto Japan
    23 Site Reference ID/Investigator# 36493 Kyoto Japan
    24 Site Reference ID/Investigator# 39123 Kyoto Japan
    25 Site Reference ID/Investigator# 54469 Maebashi Japan
    26 Site Reference ID/Investigator# 36494 Miyagi Japan
    27 Site Reference ID/Investigator# 36495 Miyazaki Japan
    28 Site Reference ID/Investigator# 36459 Nagoya Japan
    29 Site Reference ID/Investigator# 36461 Nagoya Japan
    30 Site Reference ID/Investigator# 54465 Nara Japan
    31 Site Reference ID/Investigator# 37145 Obihiro Japan
    32 Site Reference ID/Investigator# 36496 Oita Japan
    33 Site Reference ID/Investigator# 36497 Okayama Japan
    34 Site Reference ID/Investigator# 39125 Okinawa Japan
    35 Site Reference ID/Investigator# 28404 Osaka Japan
    36 Site Reference ID/Investigator# 36492 Osaka Japan
    37 Site Reference ID/Investigator# 36501 Saitama Japan
    38 Site Reference ID/Investigator# 54464 Saitama Japan
    39 Site Reference ID/Investigator# 36477 Sapporo Japan
    40 Site Reference ID/Investigator# 36478 Sapporo Japan
    41 Site Reference ID/Investigator# 36481 Sapporo Japan
    42 Site Reference ID/Investigator# 36462 Seto Japan
    43 Site Reference ID/Investigator# 36503 Shimane Japan
    44 Site Reference ID/Investigator# 36506 Shimotsuke Japan
    45 Site Reference ID/Investigator# 36504 Shizuoka Japan
    46 Site Reference ID/Investigator# 36505 Shizuoka Japan
    47 Site Reference ID/Investigator# 36499 Takatsuki Japan
    48 Site Reference ID/Investigator# 15101 Tokyo Japan
    49 Site Reference ID/Investigator# 36507 Tokyo Japan
    50 Site Reference ID/Investigator# 36508 Tokyo Japan
    51 Site Reference ID/Investigator# 36509 Tokyo Japan
    52 Site Reference ID/Investigator# 36510 Tokyo Japan
    53 Site Reference ID/Investigator# 42710 Tokyo Japan
    54 Site Reference ID/Investigator# 54470 Tokyo Japan
    55 Site Reference ID/Investigator# 36458 Toyohashi Japan
    56 Site Reference ID/Investigator# 36511 Wakayama Japan
    57 Site Reference ID/Investigator# 37144 Wakayama Japan
    58 Site Reference ID/Investigator# 36512 Yamaguchi Japan
    59 Site Reference ID/Investigator# 39124 Yamanashi Japan

    Sponsors and Collaborators

    • Mylan Inc.
    • Taisho Pharmaceutical Co., Ltd.

    Investigators

    • Study Director: Jun Kato, MD., Ph.D., Abbott Japan Co.,Ltd

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Mylan Inc.
    ClinicalTrials.gov Identifier:
    NCT01097005
    Other Study ID Numbers:
    • P10-765
    First Posted:
    Apr 1, 2010
    Last Update Posted:
    Mar 31, 2022
    Last Verified:
    Mar 1, 2015
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Keywords provided by Mylan Inc.
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details Patients will be registered using a central registration system. The investigators will register eligible patients with the registration center via FAX by 7 days after initiation of clarithromycin treatment.
    Pre-assignment Detail
    Arm/Group Title Clarithromycin
    Arm/Group Description Those with an exposure
    Period Title: Overall Study
    STARTED 466
    Analysis of Safety 441
    Analysis of NTM Lung Disease 340
    Analysis of Bacilli Negative Conversion 285
    Analysis of CGI 249
    COMPLETED 101
    NOT COMPLETED 365

    Baseline Characteristics

    Arm/Group Title Clarithromycin
    Arm/Group Description Those with an exposure
    Overall Participants 340
    Age, Customized (participants) [Number]
    <45 years
    15
    4.4%
    45-64 years
    136
    40%
    65-74 years
    126
    37.1%
    >=75 years
    62
    18.2%
    unknown
    1
    0.3%
    Sex/Gender, Customized (participants) [Number]
    Female
    256
    75.3%
    Male
    83
    24.4%
    unknown
    1
    0.3%

    Outcome Measures

    1. Primary Outcome
    Title Bacilli Negative Conversion Rate
    Description Number of participants who tested positive for Bacilli before treatment and converted to Bacilli Negative at any point during the treatment with clarithromycin
    Time Frame During the treatment with clarithromycin, from 40 days to 1232 days

    Outcome Measure Data

    Analysis Population Description
    Analysis of the bacilli negative conversion
    Arm/Group Title Clarithromycin
    Arm/Group Description Negative conversion / Yes
    Measure Participants 285
    Number [participants]
    269
    79.1%
    2. Secondary Outcome
    Title Efficacy Evaluation Using the 4-rank Scale of "Effective", "Ineffective", "Deterioration", or "Impossible" by the Investigator
    Description Number of participants who evaluated for efficacy of clarithromycin with the 4-rank Scales ("Effective", "Ineffective", "Deterioration", "Impossible")
    Time Frame When treatment with clarithromycin is discontinued, from 40 days to 1232 days

    Outcome Measure Data

    Analysis Population Description
    Analysis of Clinical Global Improvement (CGI). Number of patients with each rank scale.
    Arm/Group Title Clarithromycin
    Arm/Group Description Those with an exposure
    Measure Participants 249
    Effective
    217
    Ineffective
    13
    Deterioration
    10
    Impossible to assess
    9
    3. Secondary Outcome
    Title Bacteriological Relapse Related to Duration of Clarithromycin Administration
    Description Number of patients who have bacteriological relapse related to duration of Clarithromycin (CLR) administration after initial negative conversion
    Time Frame 36 months

    Outcome Measure Data

    Analysis Population Description
    End of study (completers). Analysis of bacteriological relapse.
    Arm/Group Title Clarithromycin
    Arm/Group Description The subjects who completed the study
    Measure Participants 101
    0-14 months CLR
    5
    1.5%
    ≥15 months CLR
    0
    0%

    Adverse Events

    Time Frame During treatment with clarithromycin up to 3.4 years
    Adverse Event Reporting Description
    Arm/Group Title Clarithromycin
    Arm/Group Description Those with an exposure
    All Cause Mortality
    Clarithromycin
    Affected / at Risk (%) # Events
    Total / (NaN)
    Serious Adverse Events
    Clarithromycin
    Affected / at Risk (%) # Events
    Total 35/441 (7.9%)
    Blood and lymphatic system disorders
    Thrombocytopenia 1/441 (0.2%) 1
    Cardiac disorders
    Arrhythmia 1/441 (0.2%) 1
    Cardiac failure acute 1/441 (0.2%) 1
    Ear and labyrinth disorders
    Vertigo positional 1/441 (0.2%) 1
    Gastrointestinal disorders
    Dysphagia 1/441 (0.2%) 1
    Large intestine polyp 1/441 (0.2%) 1
    General disorders
    Pyrexia 1/441 (0.2%) 1
    Immune system disorders
    Anti-neutrophil cytoplasmic antibody positive vasculitis 1/441 (0.2%) 1
    Infections and infestations
    Bronchopulmonary aspergillosis 1/441 (0.2%) 1
    Pneumonia 3/441 (0.7%) 3
    Bacterial infection 1/441 (0.2%) 1
    Pneumonia bacterial 4/441 (0.9%) 4
    Atypical mycobacterial infection 1/441 (0.2%) 1
    Investigations
    Weight decreased 1/441 (0.2%) 1
    Metabolism and nutrition disorders
    Hyponatraemia 1/441 (0.2%) 1
    Decreased appetite 1/441 (0.2%) 1
    Dehydration 1/441 (0.2%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Bile duct cancer 1/441 (0.2%) 1
    Colon cancer 1/441 (0.2%) 1
    Lung neoplasm malignant 1/441 (0.2%) 1
    Hepatocellular carcinoma 2/441 (0.5%) 2
    Nervous system disorders
    Somnolence 1/441 (0.2%) 1
    Loss of consciousness 1/441 (0.2%) 1
    Optic neuritis 1/441 (0.2%) 1
    Peripheral sensory neuropathy 1/441 (0.2%) 1
    Subarachnoid haemorrhage 1/441 (0.2%) 1
    Psychiatric disorders
    Disorientation 1/441 (0.2%) 1
    Renal and urinary disorders
    Nephrotic syndrome 1/441 (0.2%) 1
    Calculus urinary 1/441 (0.2%) 1
    Haematuria 1/441 (0.2%) 1
    Respiratory, thoracic and mediastinal disorders
    Interstitial lung disease 2/441 (0.5%) 2
    Alveoliltis allergic 1/441 (0.2%) 1
    Haemoptysis 2/441 (0.5%) 2
    Interstitial lung disease 2/441 (0.5%) 2
    Pneumonia aspiration 3/441 (0.7%) 3
    Pneumothorax 1/441 (0.2%) 1
    Respiratory failure 2/441 (0.5%) 2
    Skin and subcutaneous tissue disorders
    Drug eruption 1/441 (0.2%) 1
    Erythema 1/441 (0.2%) 1
    Urticaria 1/441 (0.2%) 1
    Other (Not Including Serious) Adverse Events
    Clarithromycin
    Affected / at Risk (%) # Events
    Total 0/441 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    The investigators will be granted by sponsor.

    Results Point of Contact

    Name/Title Takao Miki, Medical Affairs
    Organization Mylan EPD Japan
    Phone
    Email takao.miki@mylan.com
    Responsible Party:
    Mylan Inc.
    ClinicalTrials.gov Identifier:
    NCT01097005
    Other Study ID Numbers:
    • P10-765
    First Posted:
    Apr 1, 2010
    Last Update Posted:
    Mar 31, 2022
    Last Verified:
    Mar 1, 2015