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

Ankylosing Spondylitis Clinical Trial

— ENRADAS  

Official title:

Effects of NSAIDs on RAdiographic Damage in Ankylosing Spondylitis (ENRADAS) - a Prospective Randomised Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00715091
• Other study ID #: ENRADAS-01
• Secondary ID: EUDA-CT: 2007-00
• Status: Completed
• Phase: Phase 4
• First received: July 14, 2008
• Last updated: August 22, 2014
• Start date: September 2008
• Est. completion date: December 2013

Study information

• Verified date: August 2014
• Source: Charite University, Berlin, Germany
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Ethics CommissionGermany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 180
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ankylosing Spondylitis
• Spondylitis
• Spondylitis, Ankylosing

Intervention

Drug:
• diclophenac
continuous (daily) treatment of diclofenac cholestyramine 150 mg, divided into 75mg twice daily
• diclophenac
treatment on-demand (as needed) with diclofenac-cholestyramine 75 to 150 mg daily

Locations

Country	Name	City	State
Germany	Fachklinik Bad Bentheim	Bad Bentheim	Niedersachsen
Germany	Praxis Dr. Manger	Bamberg	Bayern
Germany	Praxis Dr. Ochs	Bayreuth	Bayern
Germany	Brandt	Berlin
Germany	Praxis Mielke	Berlin
Germany	Praxis Zinke	Berlin
Germany	Gemeinschaftspraxis Dr. Schwenke	Dresden
Germany	Rheumatologische Schwerpunktpraxis	Düsseldorf	Nordrhein-Westfalen
Germany	Universitätsklinikum DüsseldorfKlink für Endokrinologie, Diabetologie und Rheumatologie	Düsseldorf	Nordrhein-Westfalen
Germany	Praxis Dr. Rockwitz	Goslar	Niedersachsen
Germany	Praxis Dr. Pick	Grafschaft bei Bad Neuenahr-Ahrweiler
Germany	Praxis Dr. Kühne	Haldensleben
Germany	Rheumazentrum Ruhrgebiet, St. Josefs Krankenhaus	Herne
Germany	St. Josefs-Krankenhaus, Rheumatologie	Herne
Germany	Gemeinschaftspraxis Dr. von Hinüber	Hildesheim	Niedersachsen
Germany	Praxis Dr. Kapelle	Hoyerswerda
Germany	Gemeinschaftspraxis Dr. Kolitsch	Katzhütte
Germany	Praxis Dr. Kellner	München	Bayern
Germany	Praxiszentrum St. Bonifazius	München	Bayern
Germany	Gemeinschaftspraxis Dr. Gauler	Osnabrück	Niedersachsen
Germany	Gemeinschaftspraxis Dr. Göttl	Passau	Bayern
Germany	Praxis Dr. Gräßler	Pirna
Germany	Praxis Bohl-Bühler	Potsdam
Germany	Evangelisches Krankenhaus	Ratingen	Nordrhein-Westfalen
Germany	Praxis Dr. Kramer	Remscheid	Nordrhein-Westfalen
Germany	Praxis Dr. Schoo	Rheine	Nordrhein-Westfalen
Germany	Medizinische Universitätsklinik Innere Medizin	Tübingen	Baden-Württemberg
Germany	Praxis Dr. Jacki	Tübingen	Baden-Württemberg
Germany	Praxis Dr. Dockhorn	Weener	Niedersachsen
Germany	Rheumatologische Praxis Dr. Spieler	Zerbst	Sachsen-Anhalt

Sponsors (1)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Wanders A, Heijde Dv, 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		2 years	No
Secondary	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.		2 years	No
Secondary	ITT analysis of radiographic change.		2 years	No
Secondary	Change in VAS back pain, BASDAI, BASFI, BASMI, CRP.		2 years	No
Secondary	event rates of serious and non-serious adverse events will be documented and compared between the two groups.		2 years	Yes

External Links

•   Homepage, Charité, CBF, Rheumatology