A Phase 2/3 interventional study of Tacrolimus in Interstitial Pneumonitis, Polymyositis and Dermatomyositis, sponsored by Tokyo Medical and Dental University. Completed at 11 sites in Japan. Open to participants aged 16 Years to 74 Years. Per ClinicalTrials.gov, last updated 2020-03-24.
Sponsored by Tokyo Medical and Dental University · Phase 2/3, Interventional, and Treatment
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.
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.
680 studies on the registry are indexed under Lung Diseases, Interstitial; 246 are open to participants now.
This study's enrollment of 25 is below the median of 60 across 384 interventional studies indexed under Lung Diseases, Interstitial.
Browse Lung Diseases, Interstitial studies →Tokyo Medical and Dental University is the lead sponsor of 9 studies on the registry; 1 is open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Experimental treatment group
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
Historical control group
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
Exclusion Criteria:
Experimental treatment group
Historical control group
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HbA1c
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
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.
Also known as: Prograf
Overall Survival
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.
Time frame: 52 weeks
Progression-free Survival
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.
Time frame: 52 weeks
| Milestone | Prospective Investigation Group |
|---|---|
| Started | 25 |
| Completed | 17 |
| Not completed | 8 |
| Withdrew: Adverse event | 3 |
| Withdrew: Lack of efficacy | 4 |
| Withdrew: Physician decision | 1 |
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.
| percentage of participants | Prospective Investigation Group |
|---|---|
| Overall Survival | 88.0 (67.3 to 96.0) |
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.
| percentage of participants | Prospective Investigation Group |
|---|---|
| Progression-free Survival | 76.4 (51.8 to 89.5) |
Collected over All adverse events observed between the first dose and 28 days after the last dose of tacrolimus.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Prospective Investigation Group | 4/25 (16%) | 11/25 (44%) | 25/25 (100%) |
| Event | Prospective Investigation Group |
|---|---|
| Interstitial lung diseaseRespiratory, thoracic and mediastinal disorders | 6/25 |
| zosterSkin and subcutaneous tissue disorders | 1/25 |
| NocardiosisInfections and infestations | 1/25 |
| Cytomegalovirus pneumonitisRespiratory, thoracic and mediastinal disorders | 1/25 |
| Pneumocystis jiroveci pneumoniaRespiratory, thoracic and mediastinal disorders | 1/25 |
| ThrombocytopeniaBlood and lymphatic system disorders | 1/25 |
| CataractEye disorders | 1/25 |
| Acute respiratory failureRespiratory, thoracic and mediastinal disorders | 1/25 |
| PneumomediastinumRespiratory, thoracic and mediastinal disorders | 1/25 |
| AscitesGastrointestinal disorders | 1/25 |
| Event | Prospective Investigation Group |
|---|---|
| Interstitial lung diseaseRespiratory, thoracic and mediastinal disorders | 9/25 |
| ConstipationGastrointestinal disorders | 9/25 |
| Diabetes mellitusEndocrine disorders | 7/25 |
| DyslipidemiaEndocrine disorders | 7/25 |
| TremorNervous system disorders | 7/25 |
| NasopharyngitisInfections and infestations | 6/25 |
| Glucose intoleranceEndocrine disorders | 6/25 |
| HypertensionVascular disorders | 6/25 |
| DiarrheaGastrointestinal disorders | 6/25 |
| Cushingoid appearanceEndocrine disorders | 5/25 |
| Age, Continuous(years) | Prospective Investigation Group |
|---|---|
| Mean | 55.4 ± 12.0 |
| Sex: Female, Male(Participants) | Prospective Investigation Group |
|---|---|
| Female | 19 |
| Male | 6 |
The record gives a start of Jul 2007, a primary completion of Jan 2011 and a completion of Jan 2011. It does not say whether these dates are actual or estimated.
Results were first posted in Mar 2020, 9 years 2 months after primary completion.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Mar 2020. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Tacrolimus
Tokyo Medical and Dental University