Effects of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) on RAdiographic Damage in Ankylosing Spondylitis - Full Text View

Sponsor:	Charite University, Berlin, Germany
Information provided by:	Charite University, Berlin, Germany
ClinicalTrials.gov Identifier:	NCT00715091

Purpose

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.

Condition	Intervention	Phase
Ankylosing Spondylitis	Drug: diclophenac	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Effects of NSAIDs on RAdiographic Damage in Ankylosing Spondylitis (ENRADAS) - a Prospective Randomised Controlled Trial

Resource links provided by NLM:

Genetics Home Reference related topics: ankylosing spondylitis

MedlinePlus related topics: Ankylosing Spondylitis

Drug Information available for: Cholestyramine Diclofenac sodium Diclofenac potassium Diclofenac

U.S. FDA Resources

Further study details as provided by Charite University, Berlin, Germany:

Primary Outcome Measures:

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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
ITT analysis of radiographic change. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Change in VAS back pain, BASDAI, BASFI, BASMI, CRP. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
event rates of serious and non-serious adverse events will be documented and compared between the two groups. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	360
Study Start Date:	July 2008
Estimated Study Completion Date:	July 2012
Estimated Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 continuous (daily) treatment of 180 patients with diclofenac cholestyramine 150 mg (Voltaren Resinate), divided into 75mg Voltaren twice daily	Drug: diclophenac continuous (daily) treatment of diclofenac cholestyramine 150 mg, divided into 75mg twice daily Other Name: voltaren resinat
Active Comparator: 2 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.	Drug: diclophenac treatment on-demand (as needed) with diclofenac-cholestyramine 75 to 150 mg daily Other Name: Voltaren resinate

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

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00715091

Contacts

Contact: Martin Rudwaleit, MD	+49-30-8445 ext 4547	martin.rudwaleit@charite.de
Contact: In-Ho Song, MD	+49-30-8445 ext 4795	in-ho.song@charite.de

Locations

Germany
Praxis Dr. Jacki	Not yet recruiting
Tübingen, Baden-Württemberg, Germany, 72072
Contact: Swen Jacki, Dr. med.
Medizinische Universitätsklinik Innere Medizin	Not yet recruiting
Tübingen, Baden-Württemberg, Germany, 1072076
Contact: Ina Kötter, Prof. Dr. med.
Praxis Dr. Manger	Not yet recruiting
Bamberg, Bayern, Germany, 96047
Contact: Karin Manger, PD Dr. med.
Praxis Dr. Ochs	Not yet recruiting
Bayreuth, Bayern, Germany, 95445
Contact: Wolfgang Ochs, Dr. med.
Praxis Dr. Kellner	Not yet recruiting
München, Bayern, Germany, 80639
Contact: Herbert Kellner, Prof. Dr. med.
Praxiszentrum St. Bonifazius	Not yet recruiting
München, Bayern, Germany, 81541
Contact: Klaus Krüger, Prof. Dr. med.
Gemeinschaftspraxis Dr. Göttl	Not yet recruiting
Passau, Bayern, Germany, 94032
Contact: Göttl, Dr. med.
Fachklinik Bad Bentheim	Not yet recruiting
Bad Bentheim, Niedersachsen, Germany, 48455
Contact: Volker Waltz, Dr. med.
Praxis Dr. Rockwitz	Not yet recruiting
Goslar, Niedersachsen, Germany, 38640
Contact: Karin Rockwitz, Dr. med.
Gemeinschaftspraxis Dr. von Hinüber	Not yet recruiting
Hildesheim, Niedersachsen, Germany, 31134
Contact: Ulrich von Hinüber, Dr. med.
Gemeinschaftspraxis Dr. Gauler	Not yet recruiting
Osnabrück, Niedersachsen, Germany, 49076
Contact: Georg Gauler, Dr. med.
Praxis Dr. Dockhorn	Not yet recruiting
Weener, Niedersachsen, Germany, 26828
Contact: Rainer Dockhorn, Dr. med.
Universitätsklinikum DüsseldorfKlink für Endokrinologie, Diabetologie und Rheumatologie	Not yet recruiting
Düsseldorf, Nordrhein-Westfalen, Germany, 40001
Contact: Mathias Schneider, Prof. Dr. med.
Rheumatologische Schwerpunktpraxis	Not yet recruiting
Düsseldorf, Nordrhein-Westfalen, Germany, 40217
Contact: Hans-Eckhard Langer, PD Dr. med.
Evangelisches Krankenhaus	Not yet recruiting
Ratingen, Nordrhein-Westfalen, Germany, 40882
Contact: Siegfried Wassenberg, Dr. med.
Praxis Dr. Kramer	Not yet recruiting
Remscheid, Nordrhein-Westfalen, Germany, 42897
Contact: Gerd Kramer, Dr. med.
Praxis Dr. Schoo	Not yet recruiting
Rheine, Nordrhein-Westfalen, Germany, 48431
Contact: Ulrich Schoo, Dr. med.
St. Josefs-Stift	Not yet recruiting
Sendenhorst, Nordrhein-Westfalen, Germany, 48324
Contact: Michael Hammer, Prof. Dr. med.
Rheumatologische Praxis Dr. Spieler	Not yet recruiting
Zerbst, Sachsen-Anhalt, Germany, 39261
Contact: Wolfgang Spieler, Dr. med.
Praxis Mielke	Not yet recruiting
Berlin, Germany, 12627
Contact: Mielke, MD 0049-30-994 ext 21 22
Brandt	Not yet recruiting
Berlin, Germany, 12163
Contact: Jan Brandt, Dr. 0049-30 793 ext 5480 brandt.rheumatologie@arcor.de
Principal Investigator: Jan Brandt, PD Dr.
Praxis Zinke	Not yet recruiting
Berlin, Germany, 13055
Contact: Silke Zinke, MD 0049-30-98695 ext 231 dr.silke.zinke@t-online.de
Gemeinschaftspraxis Dr. Schwenke	Not yet recruiting
Dresden, Germany, 01109
Contact: Rainer Schwenke, PD Dr. med.
Praxis Dr. Pick	Not yet recruiting
Grafschaft bei Bad Neuenahr-Ahrweiler, Germany, 53501
Contact: Dorothea Pick, Dr. med.
Praxis Dr. Kühne	Not yet recruiting
Haldensleben, Germany, 39340
Contact: Cornelia Kühne, Dr. med.
St. Josefs-Krankenhaus, Rheumatologie	Not yet recruiting
Herne, Germany, 44652
Contact: Jürgen Braun, Prof. Dr. med.
Rheumazentrum Ruhrgebiet, St. Josefs Krankenhaus	Not yet recruiting
Herne, Germany, 44652
Contact: Juergen Braun, MD, Prof. 0049-232559 ext 2138 j.braun@rheumazentrum-ruhrgebiet.de
Contact: Annette Tengelmann 0049-232559 ext 2138 tengelmann@rheumazentrum-ruhrgebiet.de
Principal Investigator: Juergen Braun, MD, Prof.
Praxis Dr. Kapelle	Not yet recruiting
Hoyerswerda, Germany, 02977
Contact: Andreas Kapelle, Dr. med.
Gemeinschaftspraxis Dr. Kolitsch	Not yet recruiting
Katzhütte, Germany, 98746
Contact: Knut Kolitsch, Dr. med.
Praxis Dr. Gräßler	Not yet recruiting
Pirna, Germany, 01796
Contact: Anett Gräßler, Dr. med.
Praxis Bohl-Bühler	Not yet recruiting
Potsdam, Germany, 14469
Contact: Martin Bohl-Bühler, MD 0049-331- 647352 ext 1 info@Rheumahaus.de

Sponsors and Collaborators

Charite University, Berlin, Germany

Investigators

Principal Investigator:	Martin Rudwaleit, MD	Charité University, Berlin, Germany
Principal Investigator:	Joachim Sieper, MD	Charité University, Berlin, Germany
Principal Investigator:	Jürgen Braun, MD	Rheumazentrum Ruhrgebiet, Herne, Germany

More Information

Additional Information:

Homepage, Charité, CBF, Rheumatology This link exits the ClinicalTrials.gov site

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.

Responsible Party:	PD Dr. med Martin Rudwaleit, Rheumatology, Med. Clinic I, Charite University, Berlin, Germany
ClinicalTrials.gov Identifier:	NCT00715091 History of Changes
Other Study ID Numbers:	ENRADAS-01, EUDA-CT: 2007-007637-39
Study First Received:	July 14, 2008
Last Updated:	July 29, 2008
Health Authority:	Germany: Ethics Commission; Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Charite University, Berlin, Germany:

NSAIDS
ankylosing spondylitis
SpA
Spondyloarthritis
radiographic changes

Additional relevant MeSH terms:

Spondylitis
Spondylitis, Ankylosing
Bone Diseases, Infectious
Infection
Bone Diseases
Musculoskeletal Diseases
Spinal Diseases
Spondylarthropathies
Spondylarthritis
Ankylosis
Joint Diseases
Arthritis
Anti-Inflammatory Agents
Diclofenac
Anti-Inflammatory Agents, Non-Steroidal

Cholestyramine Resin
Therapeutic Uses
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antirheumatic Agents
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Cyclooxygenase Inhibitors

ClinicalTrials.gov processed this record on February 09, 2012