E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Exacerbation Aigues de la Ffibrose Pulmonaire Idiopatique chez les patients adultes. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10067761 |
E.1.2 | Term | Exacerbation of idiopathic pulmonary fibrosis |
E.1.2 | System Organ Class | 100000004855 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of CYC associated with corticosteroid compared to corticosteroid alone on "early" survival. Criteria: all cause mortality rate at M3. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of CYC associated with corticosteroid compared to corticosteroid alone on - Overall Survival at M6 and M12 - Respiratory disease-specific mortality at M3 and M6 - Respiratory Morbidity between M0 and M6 - Chest high resolution computed tomography features at M3 and M6 compared to M0 To evaluate prognosis factors of AE-IPF To compare the safety of the two arms of treatment
To evaluate prognosis factors in AE-IPF. Some prognosis factors have been suggested by retrospective study. We will evaluate their link with 3-months mortality. - PFTs results before AE-IPF - Time to visit after clinical worsening - Laboratory evaluation (LDH, CRP) at AE diagnosis - PaO2 at AE diagnosis - Chest HRCT features at AE diagnosis (see Appendix 3) - Time to dispense treatment of AE-IPF
To compare the safety of the two arms of treatment
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) ? >or=8 years of age 2) Definite or probable IPF diagnosis defined on 2011 international recommendations (See Appendix 1)(6). 3) Definite or suspicion of AE defined by IPFnet (2) criteria after exclusion of alternative diagnosis of acute worsening. The definition of AE is as following: - Previous or concurrent diagnosis of IPF - unexplained worsening or development of dyspnea within 30 days - high resolution computed tomography with new bilateral ground glass abnormality and / or consolidation superimposed on a background reticular or honeycomb pattern consistent with usual interstitial pattern - No evidence of pulmonary infection by endotracheal aspirate or bronchoalveolar lavage - exclusion of alternative causes including: left heart failure, pulmonary embolism, indentifiable cause of acute lung injury 4) Efficient contraceptive method 5) Affiliation to the social security 6) Able to understand and sign a written informed consent form
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E.4 | Principal exclusion criteria |
1) Identified etiology for acute worsening (i.e.: infectious disease) 2) Known hypersensitivity or contra-indication to CYC or to any component of the study treatment 3) Patient on mechanical ventilation 4) Active bacterial, viral, fungal or parasitic infection 5) Active cancer 6) Patient on a lung transplantation waiting list 7) Treatment with CYC in the last 12 months 8) Patient participating to another clinical trial 9) Documented pregnancy or lactation
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy outcome variable: All cause mortality rate at M3. The choice of mortality rate at 3 months as primary assessment criteria is driven by the most frequent information obtained from retrospective series.
Secondary efficacy outcome variables Overall survival at M6 and M12 Mortality link to the respiratory disease at M3 and M6 Morbidity defined as any of listed event occurring between M0 and M6: Worsening dyspnea (0-100-mm visual analogue (VAS) scale anchored with 0 ''no breathlessness'' and 10 or 100 ''worst imaginable breathlessness". Worsening is defined an absolute decrease of 10 mm) Or Increase need of supplemental oxygen of more than 3l/min to obtained a SaO2 > 90% or decrease of PaO2 of more than 10 mmHg with the same rate of flow supplemental oxygen Or Decrease FVC of more than 10% of predicted value Or Decrease diffuse capacity for carbon monoxide (DLCO) of more than 15% pred. Chest HRCT at M3 and M6: variation of global extent of interstitial features (Appendix 3) between M0 and M3, and between M0 and M6. Evaluation of prognosis factors Link between 3-month mortality and the following variables PFTs results before AE-IPF Time to visit after clinical worsening Laboratory evaluation (LDH, CRP) at AE-IPF diagnosis PaO2 at AE-IPF diagnosis Chest HRCT features at AE-IPF diagnosis Time to dispense treatment of AE-IPF Safety outcome measures between M0 and M6 Clinical laboratory evaluation (blood count, serum creatinin measurement) according to Common Terminology Criteria for Adverse Envent (CTCAE) (25). Hemorrhagic cystitis (occurence of hematuria on urine dipstick and pelvic pain and/or dysuria should lead to cystoscopy) Infectious disease Diabetes mellitus (capillary blood glucose monitoring and fasting plasma glucose > 1.26 g/l) Hypertension (Blood pressure > 160/100 mmHg)
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |