Investigation in Myositis-associated Pneumonitis of Prednisolone And Concomitant Tacrolimus (IMPPACT)
|ClinicalTrials.gov Identifier: NCT00504348|
Recruitment Status : Completed
First Posted : July 20, 2007
Last Update Posted : November 17, 2017
|Condition or disease||Intervention/treatment||Phase|
|Interstitial Pneumonitis Polymyositis Dermatomyositis||Drug: Tacrolimus||Phase 2 Phase 3|
Interstitial pneumonia (IP) is a common complication of and has a significant impact on the prognosis of patients with polymyositis (PM) and dermatomyositis (DM). Reported prevalence of IP in PM/DM patients varies between 23 to 65% depending on criteria applied as well as on clinical settings of studied cohorts, and an earlier overview and a later study reported its high short-term mortality.
However, treatment for this grave complication has not yet been either established or even been prospectively investigated. Glucocorticoids, while long been considered as the first-line drugs, is effective in less than 50% of patients. Furthermore, the mortality of these glucocorticoids-resistant patients does not improve even if immunosuppressive drugs are later added.
Recently, we and others reported retrospective data which suggest that either an early addition of immunosuppressive drugs to glucocorticoids or the combined use of glucocorticoids and immunosuppressive drugs from the initial treatment may improve the survival of PM/DM patients. To save lives of PM/DM-IP patients, desperate treating physicians have started using this approach, strongly urging the conduct of prospective studies to investigate the superiority of this approach over glucocorticoids alone. At the same time, it was considered not ethically appropriate to conduct a prospective study with a concurrent controlled group receiving glucocorticoids alone given the presence of the PM/DM-IP subtype with rapidly progressive course and high short-term mortality if treated with glucocorticoids alone and the absence of useful demographic or bio-markers which could distinguish patients with this subtype early. Among immunosuppressive drugs used in the treatment of PM/DM-IP, tacrolimus has recently been suggested to be effective even for those patients who are resistant to cyclosporine or cyclosphosphamide.
To investigate whether the combined initial treatment of glucocorticoids and tacrolimus is superior to glucocorticoids alone in PM/DM-IP patients, we conducted a multicenter clinical trial to evaluate the efficacy and safety of a combination treatment of glucocorticoids and tacrolimus for 1 year in patients with newly developed active PM/DM-IP or its relapse by comparing against clinical outcome of historical control patients who were treated with glucocorticoid alone as an initial treatment.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||26 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||July 2007|
|Actual Primary Completion Date :||January 2011|
|Actual Study Completion Date :||January 2011|
Experimental: Prospective investigation group
Tacrolimus treatment is to be initiated at the starting dose of 0.075mg/kg/day, adjusted to maintain its whole blood trough levels between 5 and 10 ng/mL for 52 weeks. All patients are to receive glucocorticoids with the starting doses equivalent to between 0.6 and 1.0 mg/kg/day of prednisolone which are to be continued for the first 28 days after which be subsequently tapered according to a predefined guideline. Up to two courses of pulse intravenous glucocorticoid therapy are allowed during that period.
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
- Overall survival [ Time Frame: 52 weeks ]Overall survival (OS) was calculated from the day on which the protocol treatment was started until death due to any cause. Participants still alive were censored at the date they were last known to be alive.
- Progression [ Time Frame: 52 weeks ]Patients were considered to have reached the progression if they died, or if they met all the following criteria; (1) ≥10% decline from baseline FVC or ≥15mmHg increase in baseline resting P(A-a)O2, (2) a worsening of interstitial pneumonitis findings by chest CT compared to the most recent study, confirmed by a radiologist, and (3) exclusion of pneumocystis pneumonia, cytomegalovirus pneumonia, and other pulmonary infection on clinical ground.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00504348
|Hokkaido University Hospital|
|Sapporo, Hokkaido, Japan, 060-8648|
|Tsukuba University Hospital|
|Tsukuba, Ibaraki, Japan, 305-8576|
|Osaka Minami Medical Center|
|Kawachi-Nagano, Osaka, Japan, 586-8521|
|Juntendo University Hospital|
|Bunkyo-ku, Tokyo, Japan, 113-8431|
|Tokyo Medical and Dental University Hospital|
|Bunkyo-ku, Tokyo, Japan, 113-8519|
|The University of Tokyo Hospital|
|Bunkyo-ku, Tokyo, Japan, 113-8655|
|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|
|Principal Investigator:||Nobuyuki Miyasaka, MD, PhD||Tokyo Medical and Dental University|