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

NCT ID: NCT00715091

Last Updated: 2014-08-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-09-30
• Study Completion Date: 2013-12-31

Brief Summary

This is a randomised, controlled, multi-centre clinical trial on AS patients. Experimental intervention: continuous (daily) treatment with diclofenac cholestyramine 150 mg (Voltaren Resinate), divided into 75mg Voltaren twice dailyControl intervention: treatment on-demand (as needed) 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.

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 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.

Conditions

Ankylosing Spondylitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

continuous (daily) treatment with diclofenac cholestyramine 150 mg (Voltaren Resinate), divided into 75mg Voltaren twice daily

Group Type: EXPERIMENTAL

diclophenac

Intervention Type: DRUG

continuous (daily) treatment of diclofenac cholestyramine 150 mg, divided into 75mg twice daily

2

treatment on-demand (as needed) with diclofenac-cholestyramine 75 to 150 mg (Voltaren Resinate). The treatment strategy of the control intervention (on-demand) reflects current clinical practice in AS.

Group Type: ACTIVE_COMPARATOR

diclophenac

Intervention Type: DRUG

treatment on-demand (as needed) with diclofenac-cholestyramine 75 to 150 mg daily

Interventions

diclophenac

continuous (daily) treatment of diclofenac cholestyramine 150 mg, divided into 75mg twice daily

Intervention Type: DRUG

diclophenac

treatment on-demand (as needed) with diclofenac-cholestyramine 75 to 150 mg daily

Intervention Type: DRUG

Other Intervention Names

voltaren resinat; Voltaren resinate

Eligibility 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 abuse of "hard" drugs or alcoholism
• Concomitant treatment with steroids, TNF-blockers, other DMARDs

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Charite University, Berlin, Germany

OTHER

Sponsor Role: lead

Responsible Party

J. Sieper

Prof.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Martin Rudwaleit, MD

Role: PRINCIPAL_INVESTIGATOR

Charité University, Berlin, Germany

Joachim Sieper, MD

Role: PRINCIPAL_INVESTIGATOR

Charité University, Berlin, Germany

Jürgen Braun, MD

Role: PRINCIPAL_INVESTIGATOR

Rheumazentrum Ruhrgebiet, Herne, Germany

Locations

Medizinische Universitätsklinik Innere Medizin

Tübingen, Baden-Wurttemberg, Germany

Praxis Dr. Jacki

Tübingen, Baden-Wurttemberg, Germany

Praxis Dr. Manger

Bamberg, Bavaria, Germany

Praxis Dr. Ochs

Bayreuth, Bavaria, Germany

Praxis Dr. Kellner

München, Bavaria, Germany

Praxiszentrum St. Bonifazius

München, Bavaria, Germany

Gemeinschaftspraxis Dr. Göttl

Passau, Bavaria, Germany

Fachklinik Bad Bentheim

Bad Bentheim, Lower Saxony, Germany

Praxis Dr. Rockwitz

Goslar, Lower Saxony, Germany

Gemeinschaftspraxis Dr. von Hinüber

Hildesheim, Lower Saxony, Germany

Gemeinschaftspraxis Dr. Gauler

Osnabrück, Lower Saxony, Germany

Praxis Dr. Dockhorn

Weener, Lower Saxony, Germany

Universitätsklinikum DüsseldorfKlink für Endokrinologie, Diabetologie und Rheumatologie

Düsseldorf, North Rhine-Westphalia, Germany

Rheumatologische Schwerpunktpraxis

Düsseldorf, North Rhine-Westphalia, Germany

Evangelisches Krankenhaus

Ratingen, North Rhine-Westphalia, Germany

Praxis Dr. Kramer

Remscheid, North Rhine-Westphalia, Germany

Praxis Dr. Schoo

Rheine, North Rhine-Westphalia, Germany

Rheumatologische Praxis Dr. Spieler

Zerbst, Saxony-Anhalt, Germany

Brandt

Berlin, , Germany

Praxis Mielke

Berlin, , Germany

Praxis Zinke

Berlin, , Germany

Gemeinschaftspraxis Dr. Schwenke

Dresden, , Germany

Praxis Dr. Pick

Grafschaft Bei Bad Neuenahr-Ahrweiler, , Germany

Praxis Dr. Kühne

Haldensleben I, , Germany

Rheumazentrum Ruhrgebiet, St. Josefs Krankenhaus

Herne, , Germany

St. Josefs-Krankenhaus, Rheumatologie

Herne, , Germany

Praxis Dr. Kapelle

Hoyerswerda, , Germany

Gemeinschaftspraxis Dr. Kolitsch

Katzhütte, , Germany

Praxis Dr. Gräßler

Pirna, , Germany

Praxis Bohl-Bühler

Potsdam, , Germany

Countries

Germany

References

Wanders A, Heijde Dv, Landewe R, Behier 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. doi: 10.1002/art.21054.

Reference Type: BACKGROUND

PMID: 15934081 (View on PubMed)

Hartl A, Sieper J, Syrbe U, Listing J, Hermann KG, Rudwaleit M, Poddubnyy D. Serum levels of leptin and high molecular weight adiponectin are inversely associated with radiographic spinal progression in patients with ankylosing spondylitis: results from the ENRADAS trial. Arthritis Res Ther. 2017 Jun 15;19(1):140. doi: 10.1186/s13075-017-1350-9.

Reference Type: DERIVED

PMID: 28619118 (View on PubMed)

Sieper J, Listing J, Poddubnyy D, Song IH, Hermann KG, Callhoff J, Syrbe U, Braun J, Rudwaleit M. Effect of continuous versus on-demand treatment of ankylosing spondylitis with diclofenac over 2 years on radiographic progression of the spine: results from a randomised multicentre trial (ENRADAS). Ann Rheum Dis. 2016 Aug;75(8):1438-43. doi: 10.1136/annrheumdis-2015-207897. Epub 2015 Aug 4.

Reference Type: DERIVED

PMID: 26242443 (View on PubMed)

Other Identifiers

EUDA-CT: 2007-007637-39

Identifier Type: -

Identifier Source: secondary_id

ENRADAS-01

Identifier Type: -

Identifier Source: org_study_id