Investigation in Myositis-associated Pneumonitis of Prednisolone And Concomitant Tacrolimus (IMPPACT)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2010 by Tokyo Medical and Dental University.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborators:
Japan Medical Association
Astellas Pharma Inc
Information provided by:
Tokyo Medical and Dental University
ClinicalTrials.gov Identifier:
NCT00504348
First received: July 19, 2007
Last updated: July 28, 2010
Last verified: July 2010
  Purpose

The purpose of the study is to evaluate the efficacy and safety of the combination treatment of tacrolimus and corticosteroid in polymyositis/dermatomyositis patients with interstitial pneumonitis with comparison against corticosteroid-treated historical controls.


Condition Intervention Phase
Interstitial Pneumonitis
Polymyositis
Dermatomyositis
Drug: Tacrolimus
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label Clinical Trial of the Combination Treatment of Tacrolimus and Corticosteroid in Polymyositis/Dermatomyositis Patients With Interstitial Pneumonitis, With Comparison Against Corticosteroid-treated Historical Controls

Resource links provided by NLM:


Further study details as provided by Tokyo Medical and Dental University:

Primary Outcome Measures:
  • All cause mortality [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Progression [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: July 2007
Estimated Study Completion Date: January 2011
Estimated Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Tacrolimus
    Start at the standard starting dose of 0.075mg/kg/day divided into two doses, then adjust doses based on clinical response and tolerability, but maintain whole blood trough levels between 5 to 10 ng/mL and total daily doses equal to or below 0.3mg/kg.
    Other Name: Prograf
  Eligibility

Ages Eligible for Study:   16 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Experimental treatment group

  1. Diagnosis of definite or probable polymyositis or dermatomyositis by criteria of Bohan et al, or of clinically-amyopathic dermatomyositis by the definition proposed by Sontheimer et al
  2. High-resolution CT findings consistent with interstitial pneumonitis, confirmed by a radiologist. If consolidation is the only abnormal findings, the patient must have pathologically documented evidence of interstitial pneumonitis of other histological type than cryptogenic organizing pneumonia/bronchiolitis obliterans organizing pneumonia (the patient could have more than one histological type including cryptogenic organizing pneumonia/bronchiolitis obliterans organizing pneumonia)
  3. Meet two or more of the following criteria (must include 1) 1. Serum KL-6 above the upper normal limit 2. Presence of dyspnea on exertion (grade 2 on the Magnitude of Task component of the Mahler Modified Dyspnea Index 3. PaO2 of less than 80 mmHg while breathing ambient air at rest, not accompanied by abnormal increase of PaCO2 4. Vital capacity < 80% predicted, or diffusing capacity for carbon monoxide < 65% predicted 5. Meet at least one of the following condition over the 12-week period (84 days) prior to the initiation of the study drug

    • Decrease in either % forced vital capacity or % diffusing capacity for carbon monoxide of 10% or more
    • Worsening of interstitial pneumonitis findings by chest CT, confirmed by a radiologist
  4. 16 to 74 years of age

Historical control group

  1. Diagnosis of definite or probable polymyositis or dermatomyositis by criteria of Bohan et al, or of clinically-amyopathic dermatomyositis by the definition proposed by Sontheimer et al
  2. High-resolution CT findings consistent with interstitial pneumonitis, confirmed by a radiologist. If consolidation is the only abnormal findings, the patient must have pathologically documented evidence of interstitial pneumonitis of other histological type than cryptogenic organizing pneumonia/bronchiolitis obliterans organizing pneumonia (the patient could have more than one histological type including cryptogenic organizing pneumonia/bronchiolitis obliterans organizing pneumonia)
  3. Meet two or more of the following criteria (must include 1) 1. Serum KL-6 above the upper normal limit 2. Presence of dyspnea on exertion (grade 2 on the Magnitude of Task component of the Mahler Modified Dyspnea Index 3. PaO2 of less than 80 mmHg while breathing ambient air at rest, not accompanied by abnormal increase of PaCO2 4. Vital capacity < 80% predicted, or diffusing capacity for carbon monoxide < 65% predicted 5. Meet at least one of the following condition over the 12-week period (84 days) prior to the initiation of the study drug

    • Decrease in either % forced vital capacity or % diffusing capacity for carbon monoxide of 10% or more
    • Worsening of interstitial pneumonitis findings by chest CT, confirmed by a radiologist
  4. Use of corticosteroids at doses equivalent to between 0.6 to 1.0mg/kg/day of prednisolone for 14 days or longer to treat interstitial pneumonitis on or after the day when the inclusion criteria (3) was met (up to two courses of pulse IV corticosteroid therapy within the first 28 days are allowed)
  5. 16 to 74 years of age

Exclusion Criteria:

Experimental treatment group

  1. Use of corticosteroids at doses equivalent to or higher than prednisolone 0.6mg/kg/day within 4 weeks (28 days) prior to the initiation of the study drug
  2. Use of immunosuppressive agents other than corticosteroids within 12 weeks (84 days) prior to the initiation of the study drug
  3. Could not exclude the following conditions on clinical ground: drug-induced pneumonitis, occupational lung disease, hypersensitivity pneumonitis, radiation-induced lung injury
  4. Presence of end-stage interstitial pneumonitis as identified on the basis of a vital capacity < 45% predicted, diffusing capacity for carbon monoxide < 30% predicted, or lung CT with predominantly honeycombing appearance
  5. Presence of pancreatitis
  6. Presence of diabetes mellitus with the exception of glucocorticoid-induced one that is well-controlled (HbA1c < 6.5%)
  7. Serum creatinine of 1.5 mg/dL or above
  8. Presence of liver dysfunction (AST(GOT) or ALT (GPT) greater than 2.5 times the upper limit of normal) with the exception of the one that is considered to be due to myositis and is accompanied by the elevation of muscle enzymes above the upper limit of normal
  9. Serum potassium above the upper limit of normal
  10. Presence of ischemic heart disease, arrhythmia requiring treatment, congestive heart failure, or pulmonary hypertension requiring treatment
  11. Presence or history of malignancy with the exception of those without relapse off treatment for 5 years or longer
  12. Presence of serious active infection
  13. Presence of active hepatitis B, hepatitis C, or HIV infection
  14. History of severe drug hypersensitivity reaction
  15. Patients who are pregnant or breast-feeding, or patients who intend to or whose spouses intend to conceive during the course of the study, including the follow-up period
  16. Participation in another clinical trial or post-marketing clinical study within 26 weeks (182 days) prior to screening
  17. Other medical condition which, in the investigator`s judgment, may be associated with increased risk to the subject or may interfere with study assessments or outcomes

Historical control group

  1. Use of immunosuppressive agents other than corticosteroids within 12 weeks (84 days) prior to or 2 weeks (14 days) after the corticosteroid treatment as defined by the inclusion criteria (4) is initiated
  2. Could not exclude the following conditions on clinical ground: drug-induced pneumonitis, occupational lung disease, hypersensitivity pneumonitis, radiation-induced lung injury
  3. Presence of end-stage interstitial pneumonitis as identified on the basis of a vital capacity < 45% predicted, diffusing capacity for carbon monoxide < 30% predicted, or lung CT with predominantly honeycombing appearance
  4. Presence of pancreatitis
  5. Presence of diabetes mellitus with the exception of glucocorticoid-induced one that is well-controlled (HbA1c < 6.5%)
  6. Serum creatinine of 1.5 mg/dL or above
  7. Presence of liver dysfunction (AST(GOT) or ALT (GPT) greater than 2.5 times the upper limit of normal) with the exception of the one that is considered to be due to myositis and is accompanied by the elevation of muscle enzymes above the upper limit of normal
  8. Serum potassium above the upper limit of normal
  9. Presence of ischemic heart disease, arrhythmia requiring treatment, congestive heart failure, or pulmonary hypertension requiring treatment
  10. Presence or history of malignancy with the exception of those without relapse off treatment for 5 years or longer
  11. Presence of serious active infection including active hepatitis B, hepatitis C, or HIV infection
  12. Other medical condition which, in the investigator`s judgment, may be associated with increased risk to the subject or may interfere with study assessments or outcomes
  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: NCT00504348

Locations
Japan
Hokkaido University Hospital
Sapporo, Hokkaido, Japan, 060-8648
Tsukuba University Hospital
Tsukuba, Ibaraki, Japan, 305-8576
Osaka Minami Medical Center
Kawachinagano, Osaka, Japan, 586-8521
The University of Tokyo Hospital
Bunkyo-ku, Tokyo, Japan, 113-8655
Tokyo Medical and Dental University Hospital
Bunkyo-ku, Tokyo, Japan, 113-8519
Juntendo University Hospital
Bunkyo-ku, Tokyo, Japan, 113-8431
Keio University Hospital
Shinjuku-ku, Tokyo, Japan, 160-8582
International Medical Center of Japan
Shinjuku-ku, Tokyo, Japan, 162-8655
Chiba University Hospital
Chiba, Japan, 260-8677
Nagasaki University Hospital of Medicine and Dentistry
Nagasaki, Japan, 852-8501
Tokushima University Hospital
Tokushima, Japan, 770-8503
Sponsors and Collaborators
Tokyo Medical and Dental University
Japan Medical Association
Astellas Pharma Inc
Investigators
Principal Investigator: Nobuyuki Miyasaka, MD, PhD Tokyo Medical and Dental University
  More Information

No publications provided

Responsible Party: Nobuyuki Miyasaka, MD, PhD, Professor and Chairman, Dept of Medicine and Rheumatology, Tokyo Medical and Dental University
ClinicalTrials.gov Identifier: NCT00504348     History of Changes
Other Study ID Numbers: IICT-FK506-01
Study First Received: July 19, 2007
Last Updated: July 28, 2010
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by Tokyo Medical and Dental University:
Interstitial pneumonitis
Polymyositis
Dermatomyositis
Tacrolimus
Corticosteroids
Interstitial pneumonitis associated with polymyositis or dermatomyositis

Additional relevant MeSH terms:
Polymyositis
Dermatomyositis
Pneumonia
Lung Diseases, Interstitial
Myositis
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Connective Tissue Diseases
Skin Diseases
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 31, 2014