SarcoidosisPhase 3GRANULOMANCT00872612
Trial for the Diagnosis of Sarcoidosis
A Phase 3 study testing EUS-FNA/EBUS-TBNA + BAL and EBB + TBLB + BAL in people with Sarcoidosis, run by Leiden University Medical Center at 15 sites in 6 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sarcoidosis
- What is being tested?
- EUS-FNA/EBUS-TBNA + BAL and EBB + TBLB + BAL
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 304 participants
- Where
- 15 sitesin 6 countries
- Study dates
- Mar 2009to May 2012
- 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
- Patients with suspected pulmonary sarcoidosis stage I/ II
- Age > 18 years
- Both males and females
- Written informed consent is obtained.
Who cannot join
- 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
Trial locations and contacts
15 sites in 6 countries.
15 sites in 6 countries
Netherlands7 sites
Rijnstaete Ziekenhuis
Arnhem, Gelderland
St. Catharina Ziekenhuis
Eindhoven, North Brabant
Pulmonary Department, Leiden University Medical Center
Leiden, South Holland, 2300 RC
Radboud Universitair Medisch Centrum
Nijmegen, Gelderland
Erasmus Medisch Centrum
Rotterdam, South Holland, 3015 CE
St. Franciscus Ziekenhuis
Rotterdam, South Holland
Medisch Centrum Haaglanden
The Hague, South Holland
Germany2 sites
Hospital Grosshansdorf
Großhansdorf, Schleswig-Holstein, 22927
Thoraxklinik Heidelberg
Heidelberg, Baden-Wurttemberg, 69126
Poland2 sites
University hospital Krakow, J.P. II
Krakow
Sokołowski Pulmonary Hospital
Zakopane
United Kingdom2 sites
Royal Brompton Hospital
London, London
Chelsea and Westminster hospital
London, SW10 9NH
About this study
Official title: Endosonography (EUS and EBUS) vs Conventional Bronchoscopy for the Diagnosis of Sarcoidosis: a Randomized Trial
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.
Read the 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:
- A clinical and radiological suspicion of sarcoidosis stage I/II.
- A tissue diagnosis of disease-specific non-caseating granulomas.
- 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.
- Conditions
- Sarcoidosis
- Being tested
- EUS-FNA/EBUS-TBNA + BAL, EBB + TBLB + BAL
- Keywords
- Sarcoidosis, Diagnosis, Non-caseating granulomas, BAL, EUS-FNA, EBUS-TBNA, TBLB
- Medical subject headings
- Sarcoidosis, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EUS-FNA/EBUS-TBNA + BALProcedure or surgery
EUS-FNA = Endoscopic Ultrasound guided fine needle aspiration of mediastinal lymph nodes.
EBUS-TBNA = Endobronchial Ultrasound guided transbronchial needle aspiration of mediastinal and hilar lymph nodes.
BAL = bronchoalveolar lavage
EBB + TBLB + BALProcedure or surgery
EBB = Endobronchial biopsy TBLB = Transbronchial biopsy BAL = Bronchoalveolar lavage
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | Endosonography arm Receives: Procedure: EUS-FNA/EBUS-TBNA + BAL |
| B | Active comparator | Conventional bronchoscopy arm Receives: Procedure: EBB + TBLB + BAL |
What is being measured
The primary outcome is the main question the study is designed to answer.
The role of endosonography (EBUS/ EUS - FNA) in demonstrating non-caseating granulomas in comparison with conventional bronchoscopy (TBLB + EBB)
Measured: within a week
Secondary outcomes (3)
Assessment of complications of both the endosonography and conventional bronchoscopic workup
Measured: within 30 days
The additional value of BAL, in relation to endosonography and conventional bronchoscopy (TBLB + EBB), in diagnosing sarcoidosis
Measured: 2 weeks
Assessment of patient preference for both the endosonographic and conventional bronchoscopic work-up.
Measured: within a week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2009 (estimated)
- Study startMar 2009
- Primary completionNov 2011
- Study completionMay 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for SarcoidosisStudies of the same condition, open and under way.
- More trials run by Leiden University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 304 participants (actual)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, M.B. von Bartheld, Leiden University Medical Center
- Investigators
- M B von Bartheld, MSc, Study director, Pulmonary Department, Leiden University Medical CenterJ T Annema, MD PhD, Principal investigator, Pulmonary Department, Leiden University Medical CenterK F Rabe, MD PhD, Principal investigator, Pulmonary Department, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00872612
- Sponsor's protocol ID
- LUMC-GRANULOMA
- Acronym
- GRANULOMA
- Status last verified
- Dec 2015
- First submitted
- 30 Mar 2009
- Last updated
- 7 Dec 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 10573213Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. N Engl J Med. 2007 Nov 22;357(21):2153-65. doi: 10.1056/NEJMra071714. No abstract available.
PubMed 18032765Winterbauer 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.
PubMed 8339618Kantrow 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.
PubMed 9493649Annema 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.
PubMed 15738281Garwood 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.
PubMed 17890467von 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.
PubMed 23780458
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Endosonography (EUS and EBUS) vs Conventional Bronchoscopy for the Diagnosis of Sarcoidosis: a Randomized Trial
- ClinicalTrials.gov ID
- NCT00872612
- Acronym / sponsor ID
- GRANULOMA / LUMC-GRANULOMA
- Conditions
- Sarcoidosis
- Keywords
- Sarcoidosis, Diagnosis, Non-caseating granulomas, BAL, EUS-FNA, EBUS-TBNA, TBLB
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 304 participants (actual)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Study start
- Mar 2009
- Primary completion
- Nov 2011 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 31 Mar 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- A clinical and radiological suspicion of sarcoidosis stage I/II.
- A tissue diagnosis of disease-specific non-caseating granulomas.
- 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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Procedure: EUS-FNA/EBUS-TBNA + BALEndosonography arm |
| B | Active comparator | Procedure: EBB + TBLB + BALConventional bronchoscopy arm |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients with suspected pulmonary sarcoidosis stage I/ II
- Age > 18 years
- Both males and females
- Written informed consent is obtained.
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EUS-FNA/EBUS-TBNA + BALEUS-FNA = Endoscopic Ultrasound guided fine needle aspiration of mediastinal lymph nodes. EBUS-TBNA = Endobronchial Ultrasound guided transbronchial needle aspiration of mediastinal and hilar lymph nodes. BAL = bronchoalveolar lavage | Procedure or surgery | A |
| EBB + TBLB + BALEBB = Endobronchial biopsy TBLB = Transbronchial biopsy BAL = Bronchoalveolar lavage | Procedure or surgery | B |
Primary outcome
The role of endosonography (EBUS/ EUS - FNA) in demonstrating non-caseating granulomas in comparison with conventional bronchoscopy (TBLB + EBB)
Time frame: within a week
3 secondary outcomes
Assessment of complications of both the endosonography and conventional bronchoscopic workup
Time frame: within 30 days
The additional value of BAL, in relation to endosonography and conventional bronchoscopy (TBLB + EBB), in diagnosing sarcoidosis
Time frame: 2 weeks
Assessment of patient preference for both the endosonographic and conventional bronchoscopic work-up.
Time frame: within a week
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Dec 2015.
- Background: PubMed 10573213Costabel 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.
- Background: PubMed 18032765Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. N Engl J Med. 2007 Nov 22;357(21):2153-65. doi: 10.1056/NEJMra071714. No abstract available.
- Background: PubMed 8339618Winterbauer 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.
- Background: PubMed 9493649Kantrow 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.
- Background: PubMed 15738281Annema 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.
- Background: PubMed 17890467Garwood 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.
- Derived from this study: PubMed 23780458von 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
M B von Bartheld, MSc study director
Pulmonary Department, Leiden University Medical Center
J T Annema, MD PhD principal investigator
Pulmonary Department, Leiden University Medical Center
K F Rabe, MD PhD principal investigator
Pulmonary Department, Leiden University Medical Center
15 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing EUS-FNA/EBUS-TBNA + BAL and EBB + TBLB + BAL in people with Sarcoidosis, run by Leiden University Medical Center at 15 sites in 6 countries.
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 4 inclusion and 6 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 7 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Netherlands, Germany, Poland, United Kingdom, Belgium and 1 more country. 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. 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?
The role of endosonography (EBUS/ EUS - FNA) in demonstrating non-caseating granulomas in comparison with conventional bronchoscopy (TBLB + EBB) (time frame: within a week). 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 NCT00872612, which also lists 7 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 7 Dec 2015.