NSAIDs Added to Anti-TNF Therapy Versus Anti-TNF Therapy Alone on Progression of Structural Damage in Ankylosing Spondylitis

Ankylosing Spondylitis Clinical Trial

— CONSUL  

Official title:

COmparison of the Effect of Treatment With NSAIDs Added to Anti-TNF Therapy Versus Anti-TNF Therapy Alone on Progression of StrUctural Damage in the Spine Over Two Years in Patients With ankyLosing Spondylitis: a Randomized Controlled Multicentre Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02758782
• Other study ID #: CONSUL2016
• Status: Completed
• Phase: Phase 4
• Start date: September 2016
• Est. completion date: January 2021

Study information

• Verified date: January 2021
• Source: Charite University, Berlin, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To evaluate the impact of treatment with a non-steroidal anti-inflammatory drug (NSAID) - Celecoxib - when added to anti-tumour necrosis factor (TNF) therapy - Golimumab - as compared to anti-TNF therapy (Golimumab) alone on progression of structural damage in the spine over two years in patients with ankylosing spondylitis (AS).

Description:

The aim of the proposed trial is to evaluate the efficacy of combined treatment with a non-steroidal anti-inflammatory drug (NSAID) added to anti-tumour necrosis factor (TNF) therapy as compared to anti-TNF therapy alone on progression of structural damage in the spine over two years in patients with ankylosing spondylitis (AS). The trial consists of two phases. In the phase I (run-in phase), patients with active AS despite treatment with NSAIDs and elevated C-reactive protein will be included and treated with a TNF blocker (golimumab). Patients with good clinical response to golimumab at week 12 will be eligible for the phase II (core phase) of the study and will be randomized 1:1 to 1) golimumab + celecoxib (experimental intervention) for 2 years (weeks 12-108) or 2) golimumab alone (control intervention) also for 2 years. The primary outcome parameter will be the absolute progression of the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) - currently a standard of structural spinal damage progression evaluation in AS - over two years of therapy (weeks 12-108).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 156
• Est. completion date: January 2021
• Est. primary completion date: January 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Major Inclusion Criteria:

• Definite diagnosis of AS according to the "modified New York criteria".

• History of an inadequate response to =2 NSAIDs taken for at least 2 weeks each.

• Active disease as defined by a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) value of =4 at screening.

• Presence of at least one of the following risk factors for radiographic spinal progression:

1. Elevated C reactive protein (CRP; >5mg/l) at screening at the absence of reasons for elevated CRP other than AS;

2. Presence of = 1 syndesmophyte on prior X-rays of the spine.

• Subject is a candidate for anti-TNF therapy based on the Investigator's opinion.

• Subject is able and willing to give a written informed consent and comply with the requirements of the study protocol. Only patients who give written informed consent will be included in the trial.

• If female: either unable to bear children (postmenopausal for at least 1 year or surgically sterile) or is willing and able to practice a reliable method of contraception throughout the study and 6 months after

Inclusion Criterion for Phase II (randomized part of the study):

• adequate response to Golimumab during Phase I (referred to as decline in BASDAI)

Major Exclusion Criteria:

• For female subjects: pregnancy or lactating

• subjects with chronic inflammatory articular disease other than spondyloarthritis / AS or systemic autoimmune disease, e.g. systemic lupus erythematosus, Sjögren´s syndrome, rheumatoid arthritis.

• history of inadequate response to anti-TNF-therapy

• intolerability/hypersensitivity to one of the drugs or other components of the study medication

• presence ot total spinal ankylosis

• contraindications to anti-TNF-therapy (current or remitting clinical significant infections, tuberculosis, viral hepatitis, HIV; malignancies; demyelinating disease; vaccination with live vaccine within 3 months before, during and until 6 months after study)

• (relative) contraindications to Celecoxib therapy (uncontrolled arterial hypertension, high cardiovascular risk / history of cardiovascular events; history of gastrointestinal ulcers or relevant bleeding; known M. Crohn or ulcerative colitis)

• diagnosis of fibromyalgia

• significant lab abnormalities

Related Conditions & MeSH terms

• Ankylosing Spondylitis
• Spondylitis
• Spondylitis, Ankylosing

Intervention

Biological:
• Golimumab

Drug:
• Celecoxib

Locations

Country	Name	City	State
Germany	Rheumapraxis Kupka	Altenburg
Germany	Rheumapraxis Bayreuth Dr. Ochs	Bayreuth
Germany	Charite Universitaetsmedizin - Dpt. Rheumatology at Campus Charite Mitte	Berlin
Germany	Charite Universitaetsmedizin, Dpt. of Rheumatology at Campus Benjamin Franklin	Berlin
Germany	MVZ Drs. Mielke	Berlin
Germany	Rheumapraxis Dr. Zinke	Berlin
Germany	Rheumatologische Praxis Dr. Karberg/Brandt	Berlin
Germany	Rheumatologische Schwerpunktpraxis	Berlin
Germany	Schlossparkklinik, Dpt. of Rheumatologie	Berlin
Germany	Rheumatologische Schwerpunktpraxis an den Kreiskliniken	Burghausen
Germany	Centrum für innovative Diagnostik und Therapie Rheumatologie/Immunologie (CIRI)	Frankfurt / Main
Germany	Praxis Dr Kühne	Haldensleben I
Germany	Medizinische Hochschule, Rheumatologie	Hannover
Germany	Rheumazentrum Ruhrgebiet	Herne
Germany	Universitätsklinikum Köln, Rheumatologie	Koeln
Germany	Rheumapraxis Magdeburg	Magdeburg
Germany	Klinikum Rechts der ISAR (TU München)	München
Germany	Rheumapraxis Dr. Jacki	Tübingen
Germany	University of Tuebingen, Dpt. Rheumatology	Tübingen

Sponsors (1)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Proft F, Muche B, Listing J, Rios-Rodriguez V, Sieper J, Poddubnyy D. Study protocol: COmparison of the effect of treatment with Nonsteroidal anti-inflammatory drugs added to anti-tumour necrosis factor a therapy versus anti-tumour necrosis factor a thera — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Absolute progression of the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) over two years of therapy (weeks 12-108) in the Phase II (core phase) of the trial	Absolute progression of the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) over two years of therapy (weeks 12-108) in the Phase II (core phase) of the trial	2 years
Secondary	New syndesmophyte formation or progression of existing syndesmophytes	New syndesmophyte formation or progression of existing syndesmophytes	2 years
Secondary	Improvement of disease activity (BASDAI)	Improvement of disease activity (BASDAI)	2 years
Secondary	Improvement of disease activity (ASDAS)	Improvement of disease activity (ASDAS)	2 years
Secondary	Improvement of function (BASFI)	Improvement of function (BASFI)	2 years
Secondary	Improvement of axial mobility (BASMI)	Improvement of axial mobility (BASMI)	2 years
Secondary	Improvement of quality of life measures (ASAS Health Index)	Improvement of quality of life measures (ASAS Health Index)	2 years
Secondary	Change of the enteric microbiome profile at week 108 in comparison to baseline	Change of the enteric microbiome profile at week 108 in comparison to baseline	2 years
Secondary	Change of Berlin MRI score (SUBSTUDY)	Change of Berlin MRI score (SUBSTUDY)	2 years
Secondary	Adverse events (AE), serious AE and AE of interest until end of study	Adverse events (AE), serious AE and AE of interest until end of study	2 years