Effects of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) on RAdiographic Damage in Ankylosing Spondylitis
Information source: Charite University, Berlin, Germany
Information obtained from ClinicalTrials.gov on October 19, 2009
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Ankylosing Spondylitis
Intervention: diclophenac (Drug); diclophenac (Drug)
Phase: Phase 4
Status: Not yet recruiting
Sponsored by: Charite University, Berlin, Germany Official(s) and/or principal investigator(s):
Martin Rudwaleit, MD, Principal Investigator, Affiliation: Charité University, Berlin, Germany
Joachim Sieper, MD, Principal Investigator, Affiliation: Charité University, Berlin, Germany
Jürgen Braun, MD, Principal Investigator, Affiliation: Rheumazentrum Ruhrgebiet, Herne, Germany
Overall contact:
Martin Rudwaleit, MD, Phone: +49-30-8445, Ext: 4547, Email: martin.rudwaleit@charite.de
Summary
This is a randomised, controlled, multi-centre clinical trial on 360 AS patients.
Experimental intervention: continuous (daily) treatment of 180 patients with diclofenac
cholestyramine 150 mg (Voltaren Resinate), divided into 75mg Voltaren twice dailyControl
intervention: treatment on-demand (as needed) of 180 patients with
diclofenac-cholestyramine 75 to 150 mg (Voltaren Resinate). The treatment strategy of the
control intervention (on-demand) reflects current clinical practice in AS. Duration of
intervention per patient: 2 years Follow-up per patient: safety assessment 3 months
after termination of the trial.
Clinical Details
Official title: Effects of NSAIDs on RAdiographic Damage in Ankylosing Spondylitis (ENRADAS) - a Prospective Randomised Controlled Trial
Study design: Treatment, Randomized, Open Label, Dose Comparison, Parallel Assignment, Safety/Efficacy Study
Primary outcome: radiographic change (mean) of the spine after 2 years in the per-protocol population. Radiographs will be collected and centrally digitized. Scoring will be done by 2 readers who were blinded to treatment and sequence of the films
Secondary outcome: the proportions of patients with any progression (change in the mSASSS ≥ 1) and change in the mSASSS > smallest detectable change (SDC), i.e. change in mSASSS which is greater than the measurement error.ITT analysis of radiographic change. Change in VAS back pain, BASDAI, BASFI, BASMI, CRP. event rates of serious and non-serious adverse events will be documented and compared between the two groups.
Detailed description:
Ankylosing spondylitis (AS) is a common chronic inflammatory rheumatic disease with a
prevalence of about 0. 5%. First symptoms normally occur in young adulthood. Early in its
course, AS is dominated by chronic pain, fatigue and morning stiffness, later on by
ankylosis and loss of function. Nonsteroidal anti-inflammatory drugs (NSAID) and tumor
necrosis factor (TNF) alpha blocking agents are the only drugs with proven efficacy for
signs and symptoms. It is not clear, however, whether these drugs are also capable of
retarding or stopping structural damage, i. e. prevention of bony ankylosis. Earlier
investigations indicated that NSAIDs have, in addition to their anti-inflammatory, also an
anti-osteoproliferative effect. In this study we will investigate whether treatment with 150
mg diclofenac, a non-selective NSAID, on a daily basis (continuous treatment) over 2 years
is capable to slow down the development of bony ankylosis as compared to treatment with
75-150mg diclofenac as needed according to clinical symptoms (on-demand treatment). In this
national multi-centre randomized trial 360 patients with symptomatic AS and indication for
NSAID therapy will be enrolled in about 40 centres. The primary outcome parameter is the
proportion of patients with radiographic progression in the spine after 2 years in each
treatment arm. If continuous NSAID treatment results in less radiographic progression as
compared to on-demand treatment, a true disease modifying effect of NSAID has to be assumed
which will most likely change the place of NSAID treatment in AS.
Eligibility
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- AS according to mod. New York criteria
- Patients must have radiographic damage (at least one syndesmophyte) of the spine but
no complete ankylosis of the cervical and lumbar spine (these are patients at risk
for further and more rapid radiographic progression)
- Patients must have active disease at inclusion defined as BASDAI question 2 (related
to back pain) >= 4 (VAS, range 0-10) without NSAID treatment and with a clinical
indication for NSAID therapy based on signs and symptoms
Exclusion Criteria:
- No radiographic damage (syndesmophyte) of the spine at baseline
- Complete ankylosis of the cervical and lumbar spine
- Inactive disease
- Evidence of current or past peptic ulcer
- Current or past coronary heart disease
- Stroke or transient ischemic attack
- Uncontrolled hypertension
- Chronic renal failure (creatinine > 1. 5mg/dl)
- Impaired liver function
- Pregnancy
- Abnormal liver function (2x upper limit of normal)
- Active hepatitis B or C, chronic or acute heart failure (NYHA III or IV) -
- History of HIV infection
- History of neoplastic disease (details please refer to exclusion criteria)
- History of abuse of "hard" drugs or alcoholism
- Concomitant treatment with steroids, TNF-blockers, other DMARDs
Locations and Contacts
Martin Rudwaleit, MD, Phone: +49-30-8445, Ext: 4547, Email: martin.rudwaleit@charite.de
Brandt, Berlin 12163, Germany
Praxis Bohl-Bühler, Potsdam 14469, Germany
Praxis Mielke, Berlin 12627, Germany
Praxis Zinke, Berlin 13055, Germany
Rheumazentrum Ruhrgebiet, St. Josefs Krankenhaus, Herne 44652, Germany
Praxis Dr. Kühne, Haldensleben 39340, Germany
St. Josefs-Krankenhaus, Rheumatologie, Herne 44652, Germany
Praxis Dr. Pick, Grafschaft bei Bad Neuenahr-Ahrweiler 53501, Germany
Praxis Dr. Kapelle, Hoyerswerda 02977, Germany
Praxis Dr. Gräßler, Pirna 01796, Germany
Gemeinschaftspraxis Dr. Schwenke, Dresden 01109, Germany
Gemeinschaftspraxis Dr. Kolitsch, Katzhütte 98746, Germany
Medizinische Universitätsklinik Innere Medizin, Tübingen, Baden-Württemberg 1072076, Germany
Praxis Dr. Jacki, Tübingen, Baden-Württemberg 72072, Germany
Praxis Dr. Manger, Bamberg, Bayern 96047, Germany
Praxis Dr. Ochs, Bayreuth, Bayern 95445, Germany
Praxis Dr. Kellner, München, Bayern 80639, Germany
Praxiszentrum St. Bonifazius, München, Bayern 81541, Germany
Gemeinschaftspraxis Dr. Göttl, Passau, Bayern 94032, Germany
Praxis Dr. Rockwitz, Goslar, Niedersachsen 38640, Germany
Praxis Dr. Dockhorn, Weener, Niedersachsen 26828, Germany
Gemeinschaftspraxis Dr. Gauler, Osnabrück, Niedersachsen 49076, Germany
Gemeinschaftspraxis Dr. von Hinüber, Hildesheim, Niedersachsen 31134, Germany
Fachklinik Bad Bentheim, Bad Bentheim, Niedersachsen 48455, Germany
Praxis Dr. Kramer, Remscheid, Nordrhein-Westfalen 42897, Germany
Evangelisches Krankenhaus, Ratingen, Nordrhein-Westfalen 40882, Germany
Rheumatologische Schwerpunktpraxis, Düsseldorf, Nordrhein-Westfalen 40217, Germany
Praxis Dr. Schoo, Rheine, Nordrhein-Westfalen 48431, Germany
St. Josefs-Stift, Sendenhorst, Nordrhein-Westfalen 48324, Germany
Universitätsklinikum DüsseldorfKlink für Endokrinologie, Diabetologie und Rheumatologie, Düsseldorf, Nordrhein-Westfalen 40001, Germany
Rheumatologische Praxis Dr. Spieler, Zerbst, Sachsen-Anhalt 39261, Germany
Additional Information
Homepage, Charité, CBF, Rheumatology
Related publications: Wanders A, Heijde D, Landewé R, Béhier JM, Calin A, Olivieri I, Zeidler H, Dougados M. Nonsteroidal antiinflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis: a randomized clinical trial. Arthritis Rheum. 2005 Jun;52(6):1756-65.
Starting date: July 2008
Ending date: July 2012
Last updated: July 29, 2008
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