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OT3 - Prevention and treatment of interstitial lung disease

Observational Trial 3 (OT3) - Prevention and treatment of interstitial lung disease (lung fibrosis)

Lung fibrosis and resulting shortness of breath is one of the most important organ involvements of Systemic Sclerosis that reduces quality of life and limits daily activities. This observational trial aims to identify the current state of clinical practice for theprevention and treatment of lung fibrosis, its effect on lung function and disease progression and potential predictors for the response to therapy of the individual patient.

The following protocol gives you a brief summary of observational trial 3:

 

 PI: Gabriela RIEMEKASTEN (CHARITÉ ), Christopher DENTON (UCL)

 Investigative objective

To identify:

  • The state of clinical practice in Europe for prevention and treatment of ILD and its impact on lung function and disease progression

  • The unmet need for future therapies

  • The potential predictors and confounders for response to therapy 

 Primary endpoint(s)

Proportion of patients with 10% decline in FVC (Time Frame: 1 year)

 Secondary endpoint(s)
  • The time to a 15% decline in DLCO or a drop <55% of predicted lung function
  • The mortality due to lung fibrosis
  • The need for oxygen support 

 Exploratory endpoints

 Identification of parameters with impact on ILD progression independent of therapies, such as SSc subgroups, presence of antibodies, presence of vasculopathy, time to therapy initiation, degree of lung fibrosis defined by FVC values, age at disease onset and at treatment initiation, gender, co-morbidities and other confounders 

Safety endpoints

Incidence of drug-related adverse events, incidence of withdrawal from treatment due to drug-related adverse events 

 Participants

 Study population justification

The study population are adult and juvenile SSc patients from the EUSTAR cohort (MEDSonline database) and the jSScWG cohort

 Inclusion criteria

Adult and juvenile systemic sclerosis patients, with diagnosis according to the ACR/EULAR adult SSc criteria and PRES/ACR/EULAR juvenile SSc criteria, respectively, with or without proven ILD (by X-ray or CT scan) 
Exclusion criteria

History of exposure to silica or asbestos 

Treatment arms

Four different groups will be observed for analysis:

  • Patients receiving Cyclophosphamide
  • Patients receiving Azathioprine
  • Patients receiving Mycophenolate Mofetil
  • Patients receiving Methotrexate
  • Patients receiving no therapy 

Randomization 

No randomization (observational study) 

Follow-up 

Evaluations will be performed at baseline and every 3 months until the end of the 1- year follow-up 

Justification of recruitment centres/ countries 

The OT will be performed based on the EUSTAR database MEDSonline, which includes approximately 9,600 patients, and the jSScWG taking care of approximately 100 – 120 children and adolescents. Of the adult SSc patients, 644 patients are currently on cyclophosphamide, 595 patients on azathioprine, 345 patients on mycophenolate mofetil, and 761 on methotrexate. 

Pre-planned subgroup analyses (effect modification) 

Identification of effect modification in subgroups defined by SSc subgroups, presence of antibodies, presence of vasculopathy, time to therapy initiation, degree of lung fibrosis defined by FVC values, age at disease onset and at treatment initiation, gender, ethnical background and co-morbidities 

Strengths 

  • Prospective design including patients (i) at risk to develop ILD and (ii) with established ILD

  • Large sample size

  • Feasibility

  • Recruiting centers are highly active in the field of SSc clinical research, which guarantees a high quality and accuracy of the collected data 

Limitations 

  • Observational study

  • Recruitment from tertiary medical centers, which may lead to inclusion of

    patients suffering from more active and severe disease

  • Not all centres will provide data about BAL since this is not a standard

    diagnostic instrument 
ClinicalTrials.gov Identifier: NCT01858259

For further Information:
http://clinicaltrials.gov/ct2/show/NCT01858259?term=desscipher&rank=1