Clinical trial NCT00872612: Trial for the Diagnosis of Sarcoidosis
Official title: Endosonography (EUS and EBUS) vs Conventional Bronchoscopy for the Diagnosis of Sarcoidosis: a Randomized Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Sarcoidosis
Keywords: Sarcoidosis
Diagnosis
Non-caseating granulomas
BAL
EUS-FNA
EBUS-TBNA
TBLB
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
First posted: 2009-03-31
Enrollment: 304
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: This randomized study investigates two different diagnostic strategies for patients with suspected pulmonary sarcoidosis stage I/II.

The objective is to assess the role of endosonography (EBUS/ EUS - FNA) in demonstrating non-caseating granulomas in comparison with conventional bronchoscopy (TBLB + EBB).

Also the researchers investigate the additional value of BAL, in relation to endosonography and conventional bronchoscopy (TBLB + EBB), in diagnosing sarcoidosis.

Thirdly the researchers aim to assess the rate of complications in both the endosonography and conventional bronchoscopic workup.

Detailed description: Sarcoidosis is the most prevalent interstitial lung disease in Western-Europe and the US. The disease is most prevalent in young adults. To set the final diagnosis of sarcoidosis, the following parameters need to be present:

1. A clinical and radiological suspicion of sarcoidosis stage I/II.
2. A tissue diagnosis of disease-specific non-caseating granulomas.
3. Exclusion of possible alternative diagnoses as lung cancer or tuberculosis.

Nowadays, a bronchoscopy with lung biopsies is advised to set a tissue diagnosis of sarcoidosis. However, these biopsies are only diagnostic in 70% of the procedures and they are associated with a 3% risk of coughing up blood and a 4% risk of a lung collapse.

Since recently, a new diagnostic procedure has come available. This procedure, endo-sonography, makes it possible to biopsy lymph nodes in the chest under direct visualization and has a diagnostic accuracy of 85%. The associated risk of complications appears to be small (\<1%)

We consider the current standard for the diagnostics of sarcoidosis to be outdated, considering the clinical availability of endo-sonography. We expect that endo-sonography is more frequent diagnostic for a tissue diagnosis of sarcoidosis.

Also we hypothesize that this technique is safer and more preferred by patients.

Eligibility criteria: Inclusion Criteria:

* Patients with suspected pulmonary sarcoidosis stage I/ II
* Age \> 18 years
* Both males and females
* Written informed consent is obtained.

Exclusion Criteria:

* Patients with obvious other organ involvement of sarcoidosis where a simple diagnostic biopsy to assess granulomas can be performed.
* Löfgren's syndrome
* Inability to undergo fiberbronchoscopy, EBUS or EUS (e.g. respiratory insufficiency, esophageal stenosis
* Contraindications for a lung or nodal biopsy (e.g. coagulopathy, thrombocytopenia)
* Pregnancy
* Inability to obtain informed consent

Primary outcomes:
measure: The role of endosonography (EBUS/ EUS - FNA) in demonstrating non-caseating granulomas in comparison with conventional bronchoscopy (TBLB + EBB)
timeFrame: within a week
Secondary outcomes:
measure: Assessment of complications of both the endosonography and conventional bronchoscopic workup
timeFrame: within 30 days
measure: The additional value of BAL, in relation to endosonography and conventional bronchoscopy (TBLB + EBB), in diagnosing sarcoidosis
timeFrame: 2 weeks
measure: Assessment of patient preference for both the endosonographic and conventional bronchoscopic work-up.
timeFrame: within a week
Other outcomes:
Locations:
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Hellerup
country: Denmark
facility: Gentofte Hospital Copenhagen
state: Copenhagen
city: Heidelberg
country: Germany
facility: Thoraxklinik Heidelberg
state: Baden-Württemberg
city: Grosshansdorf
country: Germany
facility: Hospital Grosshansdorf
state: Schleswig-Holstein
city: Arnhem
country: Netherlands
facility: Rijnstaete Ziekenhuis
state: Gelderland
city: Nijmegen
country: Netherlands
facility: Radboud Universitair Medisch Centrum
state: Gelderland
city: Eindhoven
country: Netherlands
facility: St. Catharina Ziekenhuis
state: Noord-Brabant
city: Den Haag
country: Netherlands
facility: Medisch Centrum Haaglanden
state: Zuid-Holland
city: Leiden
country: Netherlands
facility: Pulmonary Department, Leiden University Medical Center
state: Zuid-Holland
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
state: Zuid-Holland
city: Rotterdam
country: Netherlands
facility: St. Franciscus Ziekenhuis
state: Zuid-Holland
city: Krakow
country: Poland
facility: University hospital Krakow, J.P. II
city: Zakopane
country: Poland
facility: Sokołowski Pulmonary Hospital
city: London
country: United Kingdom
facility: Chelsea and Westminster hospital
city: London
country: United Kingdom
facility: Royal Brompton Hospital
Study officials:
affiliation: Pulmonary Department, Leiden University Medical Center
name: M B von Bartheld, MSc
role: STUDY_DIRECTOR
affiliation: Pulmonary Department, Leiden University Medical Center
name: J T Annema, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Pulmonary Department, Leiden University Medical Center
name: K F Rabe, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Costabel U, Hunninghake GW. ATS/ERS/WASOG statement on sarcoidosis. Sarcoidosis Statement Committee. American Thoracic Society. European Respiratory Society. World Association for Sarcoidosis and Other Granulomatous Disorders. Eur Respir J. 1999 Oct;14(4):735-7. doi: 10.1034/j.1399-3003.1999.14d02.x. No abstract available.
citation: Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. N Engl J Med. 2007 Nov 22;357(21):2153-65. doi: 10.1056/NEJMra071714. No abstract available.
citation: Winterbauer RH, Lammert J, Selland M, Wu R, Corley D, Springmeyer SC. Bronchoalveolar lavage cell populations in the diagnosis of sarcoidosis. Chest. 1993 Aug;104(2):352-61. doi: 10.1378/chest.104.2.352.
citation: Kantrow SP, Meyer KC, Kidd P, Raghu G. The CD4/CD8 ratio in BAL fluid is highly variable in sarcoidosis. Eur Respir J. 1997 Dec;10(12):2716-21. doi: 10.1183/09031936.97.10122716.
citation: Annema JT, Veselic M, Rabe KF. Endoscopic ultrasound-guided fine-needle aspiration for the diagnosis of sarcoidosis. Eur Respir J. 2005 Mar;25(3):405-9. doi: 10.1183/09031936.05.00098404.
citation: Garwood S, Judson MA, Silvestri G, Hoda R, Fraig M, Doelken P. Endobronchial ultrasound for the diagnosis of pulmonary sarcoidosis. Chest. 2007 Oct;132(4):1298-304. doi: 10.1378/chest.07-0998. Epub 2007 Sep 21.
citation: von Bartheld MB, Dekkers OM, Szlubowski A, Eberhardt R, Herth FJ, in 't Veen JC, de Jong YP, van der Heijden EH, Tournoy KG, Claussen M, van den Blink B, Shah PL, Zoumot Z, Clementsen P, Porsbjerg C, Mauad T, Bernardi FD, van Zwet EW, Rabe KF, Annema JT. Endosonography vs conventional bronchoscopy for the diagnosis of sarcoidosis: the GRANULOMA randomized clinical trial. JAMA. 2013 Jun 19;309(23):2457-64. doi: 10.1001/jama.2013.5823.