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Idiopathic Pulmonary FibrosisPhase 3EXAFIPNCT02460588

Cyclophosphamide for Acute Exacerbation of Idiopathic Pulmonary Fibrosis

A Phase 3 study testing Cyclophosphamide and Corticosteroid (prednisolone) in people with Idiopathic Pulmonary Fibrosis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a major event of IPF with an annual incidence between 5 and 10% and is responsible for the death of one third of IPF patients. When AE-IPF occurs, it is associated with poor survival with an overall mortality at 3 months upper of 50%. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Idiopathic Pulmonary Fibrosis
What is being tested?
Cyclophosphamide and Corticosteroid (prednisolone)
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
120 participants
Where
1 siteFrance
Study dates
Dec 2015to Jul 2019
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • ≥18 years of age
  • Definite or probable IPF diagnosis defined on 2011 international recommendations
  • Definite or suspicion of AE defined by IPFnet criteria after exclusion of alternative diagnosis of acute worsening.
  • Efficient contraceptive method within 1 month for women and 3 months for men after the last dose of treatment
  • Affiliation to the social security
  • Able to understand and sign a written informed consent form

Who cannot join

  • Identified etiology for acute worsening (i.e. infectious disease)
  • Known hypersensitivity or contra-indication to CYC or to any component of the study treatment
  • Patient on mechanical ventilation
  • Active bacterial, viral, fungal or parasitic infection
  • Active cancer
  • Patient on a lung transplantation waiting list
Show all 9Show fewer
  • Treatment with CYC in the last 12 months
  • Patient participating to another clinical trial
  • Pregnancy or lactation

Trial locations and contacts

1 site in 1 country.

France1 site

  • Hôpital Tenon

    Paris

Other trials in France

About this study

Official title: Cyclophosphamide Added to Corticosteroid in the Treatment of Acute Exacerbation of Idiopathic Pulmonary Fibrosis: a Placebo-controlled Randomized Trial

Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a major event of IPF with an annual incidence between 5 and 10% and is responsible for the death of one third of IPF patients. When AE-IPF occurs, it is associated with poor survival with an overall mortality at 3 months upper of 50%. To date, no treatment has been proved to be effective in AE-IPF but the efficacy of cyclophosphamide (CYC) on survival has been suggested, mainly by retrospective series and needs to be confirmed. This confirmation is mandatory to improve prognosis of AE-IPF but also to avoid unsuspected deleterious effect as it as been shown with immunosuppressor in stable IPF.

Read the detailed description

Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a major event of IPF with an annual incidence between 5 and 10% and is responsible for the death of one third of IPF patients. When AE-IPF occurs, it is associated with poor survival with an overall mortality at 3 months upper of 50%. To date, no treatment has been proved to be effective in AE-IPF but the efficacy of CYC on survival has been suggested, mainly by retrospective series and needs to be confirmed. This confirmation is mandatory to improve prognosis of AE-IPF but also to avoid unsuspected deleterious effect as it as been shown with immunosuppressor in stable IPF.

Being tested
Cyclophosphamide, Placebo, Corticosteroid (prednisolone)
Medical subject headings
Idiopathic Pulmonary Fibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CyclophosphamideDrug

    Population is IPF patients with an AE who meet the inclusion and exclusion criteria defined below.

    Intravenous Cyclophosphamide (CYC), 600 mg/m² (adapted to age and renal function, maximal dose of 1.2 g) at Day 0, Day 15, M1, M2

  • PlaceboDrug

    Also called Control group

    Population is IPF patients with an AE who meet the inclusion and exclusion criteria defined below.

  • Corticosteroid (prednisolone)Drug

    Also called Both groups

    All patients will receive non experimental medication with high dose of corticosteroid.

Study groups in NCT02460588
Study groupRoleWhat they receive
Corticosteroid with placeboPlacebo comparatorPopulation is IPF patients with an AE who meet the inclusion and exclusion criteria defined below. All patients will receive non experimental medication with high dose of corticosteroid.
Receives: Drug: Placebo; Drug: Corticosteroid (prednisolone)
Corticosteroid associated with CyclophosphamideExperimentalPopulation is IPF patients with an AE who meet the inclusion and exclusion criteria defined below. All patients will receive non experimental medication with high dose of corticosteroid. Intravenous Cyclophosphamide (CYC), 600 mg/m² (adapted to age and renal function, maximal dose of 1.2 g) at Day 0, Day 15, M1, M2
Receives: Drug: Cyclophosphamide; Drug: Corticosteroid (prednisolone)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. "Early" survival

    All cause of mortality at 3 months

    Measured: 3 months

Secondary outcomes (16)

  1. Overall Survival

    Overall Survival at M6 and M12

    Measured: 6 months and 12 montns

  2. Respiratory disease-specific mortality

    Respiratory disease-specific mortality at M3 and M6

    Measured: 6 months

  3. Respiratory Morbidity

    \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% prednisolone

    Measured: 6 months

  4. Chest HRCT features (HRCT images will be scored at 5 levels)

    Chest HRCT features at M3 and M6 compared to inclusion

    Measured: 6 months

  5. Prognosis factors of AE-IPF

    PFTs results before AE-IPF

    Measured: 3 months

  6. Time to visit after clinical worsening

    Measured: 3 months

  7. Laboratory evaluation (LDH, CRP) at AE diagnosis (composite)

    Measured: 3 months

  8. Prognosis factors of AE-IPF

    PaO2 at AE diagnosis

    Measured: 3 months

  9. Prognosis factors of AE-IPF

    Chest HRCT features at AE diagnosis compared to HRCT before AE-IPF (if available)

    Measured: 3 months

  10. Prognosis factors of AE-IPF

    Chest HRCT classification before AE-IPF (definite UIP, probable UIP, indeterminate), if available

    Measured: 3 months

  11. Time to dispense treatment of AE-IPF

    Measured: 3 months

  12. Hemorrhagic cystitis (occurence of hematuria on urine dipstick and pelvic pain and/or dysuria should lead to cystoscopy)

    Measured: 6 months

  13. Number of Infectious disease

    Measured: 6 months

  14. Diabetes mellitus (capillary blood glucose monitoring and fasting plasma glucose > 1.26 g/l)

    Measured: 6 months

  15. Hypertension (Blood pressure > 160/100 mmHg)

    Measured: 6 months

  16. Clinical laboratory evaluation (blood count, serum creatinin measurement composite) according to Common Terminology Criteria for Adverse Event (CTCAE).

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jun 2015 (estimated)
  2. Study startDec 2015
  3. Primary completionJan 2019
  4. Study completionJul 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
120 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02460588
Sponsor's protocol ID
P 140908
Other IDs
2015-000492-27, 2015
Acronym
EXAFIP
Status last verified
Jun 2022
First submitted
16 Mar 2015
Last updated
30 Jun 2022
Results posted
No
Data monitoring committee
No

Publications

  • Idiopathic Pulmonary Fibrosis Clinical Research Network; Raghu G, Anstrom KJ, King TE Jr, Lasky JA, Martinez FJ. Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis. N Engl J Med. 2012 May 24;366(21):1968-77. doi: 10.1056/NEJMoa1113354. Epub 2012 May 20.

    PubMed 22607134

  • Collard HR, Moore BB, Flaherty KR, Brown KK, Kaner RJ, King TE Jr, Lasky JA, Loyd JE, Noth I, Olman MA, Raghu G, Roman J, Ryu JH, Zisman DA, Hunninghake GW, Colby TV, Egan JJ, Hansell DM, Johkoh T, Kaminski N, Kim DS, Kondoh Y, Lynch DA, Muller-Quernheim J, Myers JL, Nicholson AG, Selman M, Toews GB, Wells AU, Martinez FJ; Idiopathic Pulmonary Fibrosis Clinical Research Network Investigators. Acute exacerbations of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2007 Oct 1;176(7):636-43. doi: 10.1164/rccm.200703-463PP. Epub 2007 Jun 21.

    PubMed 17585107

  • Oishi K, Mimura-Kimura Y, Miyasho T, Aoe K, Ogata Y, Katayama H, Murata Y, Ueoka H, Matsumoto T, Mimura Y. Association between cytokine removal by polymyxin B hemoperfusion and improved pulmonary oxygenation in patients with acute exacerbation of idiopathic pulmonary fibrosis. Cytokine. 2013 Jan;61(1):84-9. doi: 10.1016/j.cyto.2012.08.032. Epub 2012 Sep 26.

    PubMed 23021430

  • Morawiec E, Tillie-Leblond I, Pansini V, Salleron J, Remy-Jardin M, Wallaert B. Exacerbations of idiopathic pulmonary fibrosis treated with corticosteroids and cyclophosphamide pulses. Eur Respir J. 2011 Dec;38(6):1487-9. doi: 10.1183/09031936.00127311. No abstract available.

    PubMed 22130770

  • Simon-Blancal V, Freynet O, Nunes H, Bouvry D, Naggara N, Brillet PY, Denis D, Cohen Y, Vincent F, Valeyre D, Naccache JM. Acute exacerbation of idiopathic pulmonary fibrosis: outcome and prognostic factors. Respiration. 2012;83(1):28-35. doi: 10.1159/000329891. Epub 2011 Aug 23.

    PubMed 21860222

  • Agarwal R, Jindal SK. Acute exacerbation of idiopathic pulmonary fibrosis: a systematic review. Eur J Intern Med. 2008 Jun;19(4):227-35. doi: 10.1016/j.ejim.2007.04.024. Epub 2008 Jan 16.

    PubMed 18471669

  • Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, Colby TV, Cordier JF, Flaherty KR, Lasky JA, Lynch DA, Ryu JH, Swigris JJ, Wells AU, Ancochea J, Bouros D, Carvalho C, Costabel U, Ebina M, Hansell DM, Johkoh T, Kim DS, King TE Jr, Kondoh Y, Myers J, Muller NL, Nicholson AG, Richeldi L, Selman M, Dudden RF, Griss BS, Protzko SL, Schunemann HJ; ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011 Mar 15;183(6):788-824. doi: 10.1164/rccm.2009-040GL.

    PubMed 21471066

  • Cottin V, Crestani B, Valeyre D, Wallaert B, Cadranel J, Dalphin JC, Delaval P, Israel-Biet D, Kessler R, Reynaud-Gaubert M, Cordier JF, Aguilaniu B, Bouquillon B, Carre P, Danel C, Faivre JB, Ferreti G, Just N, Kouzan S, Lebargy F, Marchand Adam S, Philippe B, Prevot G, Stach B, Thivolet-Bejui F; French National Reference and Competence Centers for Rare Diseases; Societe de Pneumologies de Langue Francaise. [French practical guidelines for the diagnosis and management of idiopathic pulmonary fibrosis. From the National Reference and the Competence centers for rare diseases and the Societe de Pneumologie de Langue Francaise]. Rev Mal Respir. 2013 Dec;30(10):879-902. doi: 10.1016/j.rmr.2013.09.007. Epub 2013 Oct 25. No abstract available. French.

    PubMed 24314711

  • Nalysnyk L, Cid-Ruzafa J, Rotella P, Esser D. Incidence and prevalence of idiopathic pulmonary fibrosis: review of the literature. Eur Respir Rev. 2012 Dec 1;21(126):355-61. doi: 10.1183/09059180.00002512.

    PubMed 23204124

  • Wuyts WA, Agostini C, Antoniou KM, Bouros D, Chambers RC, Cottin V, Egan JJ, Lambrecht BN, Lories R, Parfrey H, Prasse A, Robalo-Cordeiro C, Verbeken E, Verschakelen JA, Wells AU, Verleden GM. The pathogenesis of pulmonary fibrosis: a moving target. Eur Respir J. 2013 May;41(5):1207-18. doi: 10.1183/09031936.00073012. Epub 2012 Oct 25.

    PubMed 23100500

  • Martinez FJ, Safrin S, Weycker D, Starko KM, Bradford WZ, King TE Jr, Flaherty KR, Schwartz DA, Noble PW, Raghu G, Brown KK; IPF Study Group. The clinical course of patients with idiopathic pulmonary fibrosis. Ann Intern Med. 2005 Jun 21;142(12 Pt 1):963-7. doi: 10.7326/0003-4819-142-12_part_1-200506210-00005.

    PubMed 15968010

  • Collard HR, Yow E, Richeldi L, Anstrom KJ, Glazer C; IPFnet investigators. Suspected acute exacerbation of idiopathic pulmonary fibrosis as an outcome measure in clinical trials. Respir Res. 2013 Jul 13;14(1):73. doi: 10.1186/1465-9921-14-73.

    PubMed 23848435

  • Churg A, Muller NL, Silva CI, Wright JL. Acute exacerbation (acute lung injury of unknown cause) in UIP and other forms of fibrotic interstitial pneumonias. Am J Surg Pathol. 2007 Feb;31(2):277-84. doi: 10.1097/01.pas.0000213341.70852.9d.

    PubMed 17255773

  • Papiris SA, Manali ED, Kolilekas L, Kagouridis K, Triantafillidou C, Tsangaris I, Roussos C. Clinical review: idiopathic pulmonary fibrosis acute exacerbations--unravelling Ariadne's thread. Crit Care. 2010;14(6):246. doi: 10.1186/cc9241. Epub 2010 Dec 22.

    PubMed 21235829

  • Song JW, Hong SB, Lim CM, Koh Y, Kim DS. Acute exacerbation of idiopathic pulmonary fibrosis: incidence, risk factors and outcome. Eur Respir J. 2011 Feb;37(2):356-63. doi: 10.1183/09031936.00159709. Epub 2010 Jul 1.

    PubMed 20595144

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Cyclophosphamide and Corticosteroid (prednisolone) in people with Idiopathic Pulmonary Fibrosis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

"Early" survival (time frame: 3 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02460588, which also lists 27 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jun 2022.

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