PROOF-Registry New and Extended Belgium -Luxembourg

Idiopathic Pulmonary Fibrosis Clinical Trial

— PROOF-NEXT  

Official title:

A Prospective Observational Registry to Describe the Disease Course and Outcomes of Idiopathic Pulmonary Fibrosis Patients in a Real-world Clinical Setting. PROOF-Registry New and Extended Belgium -Luxembourg

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03732859
• Other study ID #: BVPSBP01
• Status: Completed
• Start date: January 9, 2018
• Est. completion date: January 9, 2022

Study information

• Verified date: February 2022
• Source: Belgian Thoracic Society
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

A Prospective Observational Registry to describe the disease course and outcomes of Idiopathic Pulmonary Fibrosis patients in a real-world clinical setting.

Description:

Idiopathic pulmonary fibrosis (IPF) is a chronic disease of unknown etiology, characterized by scar tissue (fibrosis) within the lungs. IPF is one of the most common forms of interstitial lung disease and is associated with substantial morbidity and mortality (average survival of approximately three years from the time of diagnosis)).

The epidemiology and natural history of IPF is still not completely understood. Incidence and prevalence of IPF are difficult to determine because uniform diagnostic criteria have only recently been defined. Recent data among subjects aged 50 years or older suggests an age- and sex-adjusted incidence rate ranging from 8.8 cases to 17.4 cases per 100,000 person-years in the USA. In the same population, age- and sex- adjusted prevalence ranged from 27.9 cases to 63 cases per 100,000 persons.

Familial form of IPF accounts for 0.5 to 2% of all cases of IPF. Several environmental or occupational exposures seem to be prevalent in the medical histories of patients diagnosed with the disease.

The onset of IPF symptoms is slow, but symptoms become progressively worse over time. Breathlessness upon exertion and chronic dry cough are the major symptoms. Gastro-esophageal acid reflux is present in almost 90% of patients with IPF but often occurs without symptoms.

Auscultation of the lungs reveals early inspiratory crackles, predominantly located in the lower posterior lung zones upon physical exam. Clubbing is found in approximately 50% of patients with IPF.

Quality of life of patients with IPF is impacted by the disease.

Establishing an accurate diagnosis for the patient who presents with interstitial lung disease is an essential component of management. The recent ATS/ERS/JRS/ALAT recommendations on the diagnosis and management of IPF were developed from a systematic review of the published literature. High-resolution computed tomography (HRCT) scanning has a central role in the IPF diagnostic pathway with formal designation of criteria for an HRCT pattern of Usual Interstitial Pneumonia (UIP). In the correct clinical context, a UIP pattern on HRCT is indicative of a definite diagnosis of IPF without the need for a surgical lung biopsy.

IPF presents significant associations with other cardiopulmonary disorders including coronary artery disease, pulmonary embolism, sleep apnea, respiratory infections and lung cancer. In addition, patients with IPF are at risk for 'acute exacerbations'. Acute exacerbation is defined as an acute, clinically significant respiratory deterioration characterized by evidence of new widespread alveolar abnormality. Diagnostic criteria are: previous or concurrent diagnosis of IPF; acute worsening or development of dyspnea typically < 1 mo duration; computed tomography with new bilateral ground-glass opacity and/or consolidation superimposed on a background pattern consistent with usual interstitial pneumonia pattern; deterioration not fully explained by cardiac failure or fluid overload. These acute exacerbations are responsible for 50% of deaths in IPF and may affect previously stable patients.

The clinical course of IPF is highly variable and as a result, therapeutic strategies should be highly individualized, based upon the specific patients' medical history and co-morbidities.

Pirfenidone and Nintedanib are drugs approved for the treatment of adult patients with mild to moderate idiopathic pulmonary fibrosis in the European Union. In order to complement the data collected in previous studies, we implement a registry to describe the epidemiology and natural history of IPF, as well as the quality of life of IPF patients, and use of health care resources, in Belgium and Luxembourg. This registry will also enable the collection of clinical data of patients treated with Pirfenidone or Nintedanib and other therapies used in the treatment of IPF. The registry will be implemented in collaboration with pulmonologists and expert centers in order to enable the inclusion and follow up of recently diagnosed IPF patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 575
• Est. completion date: January 9, 2022
• Est. primary completion date: November 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

Inclusion Criteria:

• Patients >18 years of age

• IPF diagnosis "definite" or "probable" (2011 ATS/ERS guidelines definitions) confirmed by a multidisciplinary team (= minimum of pulmonologist, radiologist, pathologist, all with expertise in IPF).

• Patients who agreed to participate in the registry and have completed and signed the Informed Consent Form

Exclusion Criteria:

• Patients incapable of giving informed consent

• Patients participating in a clinical trial at the time of inclusion in the registry and whose protocol does not allow participation in another trial

Related Conditions & MeSH terms

• Fibrosis
• Idiopathic Pulmonary Fibrosis
• Pulmonary Fibrosis

Locations

Country	Name	City	State
Belgium	Ziekenhuisnetwerk Antwerpen vzw	Antwerp
Belgium	Cliniques Universitaires de Bruxelles - Hôpital Erasme	Brussels
Belgium	Cliniques universitaires Saint-Luc	Brussels
Belgium	Universitair Ziekenhuis Gent	Ghent
Belgium	University Hospitals Leuven	Leuven
Belgium	Centre Hospitalier Universitaire Sart Tilman	Liège
Belgium	CHR de la Citadelle	Liège
Belgium	CHU UCL Namur asbl - site Godinne	Yvoir
Luxembourg	Centre Hospitalier de Luxembourg (CHL)/ Luxembourg Institute of Health (LIH)	Luxembourg

Sponsors (3)

Lead Sponsor	Collaborator
Belgian Thoracic Society	Boehringer Ingelheim, Roche Farma, S.A

Countries where clinical trial is conducted

Belgium,  Luxembourg, 

References & Publications (18)

American Thoracic Society; European Respiratory Society. American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med. 2002 Jan 15;165(2):277-304. Review. Erratum in: Am J Respir Crit Care Med2002 Aug 1;166(3):426. — View Citation

Baumgartner KB, Samet JM, Stidley CA, Colby TV, Waldron JA. Cigarette smoking: a risk factor for idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 1997 Jan;155(1):242-8. — View Citation

Collard HR, King TE Jr, Bartelson BB, Vourlekis JS, Schwarz MI, Brown KK. Changes in clinical and physiologic variables predict survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2003 Sep 1;168(5):538-42. Epub 2003 May 28. — View Citation

Collard HR, Ryerson CJ, Corte TJ, Jenkins G, Kondoh Y, Lederer DJ, Lee JS, Maher TM, Wells AU, Antoniou KM, Behr J, Brown KK, Cottin V, Flaherty KR, Fukuoka J, Hansell DM, Johkoh T, Kaminski N, Kim DS, Kolb M, Lynch DA, Myers JL, Raghu G, Richeldi L, Taniguchi H, Martinez FJ. Acute Exacerbation of Idiopathic Pulmonary Fibrosis. An International Working Group Report. Am J Respir Crit Care Med. 2016 Aug 1;194(3):265-75. doi: 10.1164/rccm.201604-0801CI. Review. — View Citation

Fernández Pérez ER, Daniels CE, Schroeder DR, St Sauver J, Hartman TE, Bartholmai BJ, Yi ES, Ryu JH. Incidence, prevalence, and clinical course of idiopathic pulmonary fibrosis: a population-based study. Chest. 2010 Jan;137(1):129-37. doi: 10.1378/chest.09-1002. Epub 2009 Sep 11. — View Citation

Flaherty KR, Mumford JA, Murray S, Kazerooni EA, Gross BH, Colby TV, Travis WD, Flint A, Toews GB, Lynch JP 3rd, Martinez FJ. Prognostic implications of physiologic and radiographic changes in idiopathic interstitial pneumonia. Am J Respir Crit Care Med. 2003 Sep 1;168(5):543-8. Epub 2003 May 28. — View Citation

Gan Y, Herzog EL, Gomer RH. Pirfenidone treatment of idiopathic pulmonary fibrosis. Ther Clin Risk Manag. 2011 Feb 8;7:39-47. doi: 10.2147/TCRM.S12209. — View Citation

Hubbard R, Venn A, Lewis S, Britton J. Lung cancer and cryptogenic fibrosing alveolitis. A population-based cohort study. Am J Respir Crit Care Med. 2000 Jan;161(1):5-8. — View Citation

Hubbard RB, Smith C, Le Jeune I, Gribbin J, Fogarty AW. The association between idiopathic pulmonary fibrosis and vascular disease: a population-based study. Am J Respir Crit Care Med. 2008 Dec 15;178(12):1257-61. doi: 10.1164/rccm.200805-725OC. Epub 2008 Aug 28. — View Citation

Lancaster LH, Mason WR, Parnell JA, Rice TW, Loyd JE, Milstone AP, Collard HR, Malow BA. Obstructive sleep apnea is common in idiopathic pulmonary fibrosis. Chest. 2009 Sep;136(3):772-778. doi: 10.1378/chest.08-2776. Epub 2009 Jun 30. — View Citation

Latsi PI, du Bois RM, Nicholson AG, Colby TV, Bisirtzoglou D, Nikolakopoulou A, Veeraraghavan S, Hansell DM, Wells AU. Fibrotic idiopathic interstitial pneumonia: the prognostic value of longitudinal functional trends. Am J Respir Crit Care Med. 2003 Sep 1;168(5):531-7. Epub 2003 Jun 5. — View Citation

Marshall RP, Puddicombe A, Cookson WO, Laurent GJ. Adult familial cryptogenic fibrosing alveolitis in the United Kingdom. Thorax. 2000 Feb;55(2):143-6. — View Citation

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. — View Citation

Meltzer EB, Noble PW. Idiopathic pulmonary fibrosis. Orphanet J Rare Dis. 2008 Mar 26;3:8. doi: 10.1186/1750-1172-3-8. Review. — View Citation

Nathan SD, Basavaraj A, Reichner C, Shlobin OA, Ahmad S, Kiernan J, Burton N, Barnett SD. Prevalence and impact of coronary artery disease in idiopathic pulmonary fibrosis. Respir Med. 2010 Jul;104(7):1035-41. doi: 10.1016/j.rmed.2010.02.008. Epub 2010 Mar 2. — View Citation

Panos RJ, Mortenson RL, Niccoli SA, King TE Jr. Clinical deterioration in patients with idiopathic pulmonary fibrosis: causes and assessment. Am J Med. 1990 Apr;88(4):396-404. Review. — View Citation

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, Müller NL, Nicholson AG, Richeldi L, Selman M, Dudden RF, Griss BS, Protzko SL, Schünemann 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. — View Citation

Raghu G, Freudenberger TD, Yang S, Curtis JR, Spada C, Hayes J, Sillery JK, Pope CE 2nd, Pellegrini CA. High prevalence of abnormal acid gastro-oesophageal reflux in idiopathic pulmonary fibrosis. Eur Respir J. 2006 Jan;27(1):136-42. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The first occurrence of a decrease of = 10% in percent predicted forced vital capacity (FVC) since baseline.	FVC data will be retrieved from the medical file of the participant.	overall duration of study (5 years)
Primary	The first occurrence of a decrease of = 15% in percent predicted diffusing capacity of the lung for carbon monoxide (DLCO) since baseline	DLCO data will be retrieved from the medical file of the participant.	overall duration of study (5 years)
Primary	Number of participants alive	Data on death will be retrieved from the medical file of the participant.	overall duration of study (5 years)
Primary	The evolution of percent predicted forced vital capacity (FVC)	FVC data will be retrieved from the medical file of the participant.	overall duration of study (5 years)
Primary	The evolution of percent predicted diffusing capacity of the lung for carbon monoxide (DLCO)	DLCO data will be retrieved from the medical file of the participant.	overall duration of study (5 years)
Primary	The number of acute exacerbations of IPF	Acute exacerbations of IPF data will be retrieved from the medical file of the participant.	overall duration of study (5 years)
Secondary	The number of patients per IPF treatment drug	IPF treatment drug data will be retrieved from the medical file of the participant.	overall duration of study (5 years)
Secondary	The mean initial dose per IPF treatment drug	IPF treatment drug data will be retrieved from the medical file of the participant.	overall duration of study (5 years)
Secondary	The mean number of dose changes per IPF treatment drug	IPF treatment drug data will be retrieved from the medical file of the participant.	overall duration of study (5 years)
Secondary	The number of participants who have discontinued the IPF treatment per IPF treatment drug	IPF treatment drug data will be retrieved from the medical file of the participant.	overall duration of study (5 years)
Secondary	The mean duration of treatment in days per IPF treatment drug	IPF treatment drug data will be retrieved from the medical file of the participant.	overall duration of study (5 years)
Secondary	The mean duration of dose reduction in days per IPF treatment drug	IPF treatment drug data will be retrieved from the medical file of the participant.	overall duration of study (5 years)
Secondary	The mean duration of drug interruption in days per IPF treatment drug	IPF treatment drug data will be retrieved from the medical file of the participant.	overall duration of study (5 years)
Secondary	The number of participants with lung transplantation	Lung transplantation data will be retrieved from the medical file of the participant.	overall duration of study (5 years)
Secondary	The (S)ADRs per IPF treatment reported which are possibly or probably related to the IPF treatment drug.	(S)ADR data will be retrieved from the medical file of the patient.	overall duration of study (5 years)
Secondary	The utilisation of health care resources by participants	The utilisation of health care resources will be retrieved from the medical file of the patient.	overall duration of study (5 years)
Secondary	The impact of IPF and IPF treatment on the severity of cough measured with the Cough-Visual Analogue Scale.	Cough severity in the last 2 weeks was assessed at inclusion and at every follow-up visit using the Cough-VAS, a linear visual scale with 0 mm representing 'no cough' and 100 mm.	overall duration of study (5 years)
Secondary	The impact of IPF and IPF treatment on quality of life measured with the SGRQ.	The St- George's Respiratory questionnaire (SGRQ) is a 50-item questionnaire consisting of two parts. The first part evaluates the symptoms (i.e. cough, sputum production, wheezing and breathlessness) and the second part evaluates the activities (i.e. activities causing breathlessness or limited by breathlessness) and the impacts (e.g. on employment, daily life, etc.). Each question is scored as positive (i.e. =1) or negative (i.e. =0) and the total score is expressed as a percentage where 0% represents the best possible health status and 100% the worst possible health status. A total score can be obtained as well as a score for each of the three components. Data are collected at inclusion and minimal twice a year during follow-up.	overall duration of study (5 years)
Secondary	The impact of IPF and IPF treatment on quality of life measured with the EQ-5D-5L questionnaire.	The EQ-5D-5L consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels, going from no problems to extreme problems. Only 1 option can be chosen by the patient. This decision results in a 1-digit number that expresses the level selected for that dimension: no problems (=1), slight problems(=2), moderate problems(=3), severe problems(=4) and extreme problems(=5). The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.The EQ VAS records the patient's self-rated health on a vertical visual analogue scale, where 0 mm represents 'worst health imaginable' and 100 mm representing 'best health imaginable'.; Data are collected at Inclusion and at every follow-up visit.	overall duration of study (5 years)
Secondary	The impact of IPF and IPF treatment on quality of life measured with with the K-BILD questionnaire	Patients will receive the K-BILD questionnaire measuring their health-related quality of life. The K-BILD is a 15-item self-completed questionnaire measuring the health-related quality of life (HRQL) of patients with interstitial lung disease. It consists of three domains: breathlessness and activities, psychological and chest symptoms. Each question has a seven-point response scale resulting in a total score ranging between 0 and 100 with a higher score reflecting a higher HRQL. Data are collected at inclusion and at every follow-up visit.	overall duration of study (5 years)