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

NCT00715091 | Completed Phase 4 DMC

• 2 other identifiers: ENRADAS-01EUDA-CT: 2007-007637-39
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 30

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.

Conditions

Ankylosing Spondylitis

Keywords

NSAIDS; ankylosing spondylitis; SpA; Spondyloarthritis; radiographic changes

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (4)

• 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

• ITT analysis of radiographic change.

  2 years

• Change in VAS back pain, BASDAI, BASFI, BASMI, CRP.

  2 years

• event rates of serious and non-serious adverse events will be documented and compared between the two groups.

  2 years

Study Arms (2)

1

EXPERIMENTAL

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

Drug: diclophenac

2

ACTIVE COMPARATOR

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.

Drug: diclophenac

Interventions

diclophenac DRUG

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

Also known as: voltaren resinat

1

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead

Study Sites (30)

Medizinische Universitätsklinik Innere Medizin

Tübingen, Baden-Wurttemberg, 1072076, Germany

Location

Praxis Dr. Jacki

Tübingen, Baden-Wurttemberg, 72072, Germany

Location

Praxis Dr. Manger

Bamberg, Bavaria, 96047, Germany

Location

Praxis Dr. Ochs

Bayreuth, Bavaria, 95445, Germany

Location

Praxis Dr. Kellner

München, Bavaria, 80639, Germany

Location

Praxiszentrum St. Bonifazius

München, Bavaria, 81541, Germany

Location

Gemeinschaftspraxis Dr. Göttl

Passau, Bavaria, 94032, Germany

Location

Fachklinik Bad Bentheim

Bad Bentheim, Lower Saxony, 48455, Germany

Location

Praxis Dr. Rockwitz

Goslar, Lower Saxony, 38640, Germany

Location

Gemeinschaftspraxis Dr. von Hinüber

Hildesheim, Lower Saxony, 31134, Germany

Location

Gemeinschaftspraxis Dr. Gauler

Osnabrück, Lower Saxony, 49076, Germany

Location

Praxis Dr. Dockhorn

Weener, Lower Saxony, 26828, Germany

Location

Universitätsklinikum DüsseldorfKlink für Endokrinologie, Diabetologie und Rheumatologie

Düsseldorf, North Rhine-Westphalia, 40001, Germany

Location

Rheumatologische Schwerpunktpraxis

Düsseldorf, North Rhine-Westphalia, 40217, Germany

Location

Evangelisches Krankenhaus

Ratingen, North Rhine-Westphalia, 40882, Germany

Location

Praxis Dr. Kramer

Remscheid, North Rhine-Westphalia, 42897, Germany

Location

Praxis Dr. Schoo

Rheine, North Rhine-Westphalia, 48431, Germany

Location

Rheumatologische Praxis Dr. Spieler

Zerbst, Saxony-Anhalt, 39261, Germany

Location

Brandt

Berlin, 12163, Germany

Location

Praxis Mielke

Berlin, 12627, Germany

Location

Praxis Zinke

Berlin, 13055, Germany

Location

Gemeinschaftspraxis Dr. Schwenke

Dresden, 01109, Germany

Location

Praxis Dr. Pick

Grafschaft Bei Bad Neuenahr-Ahrweiler, 53501, Germany

Location

Praxis Dr. Kühne

Haldensleben I, 39340, Germany

Location

Rheumazentrum Ruhrgebiet, St. Josefs Krankenhaus

Herne, 44652, Germany

Location

St. Josefs-Krankenhaus, Rheumatologie

Herne, 44652, Germany

Location

Praxis Dr. Kapelle

Hoyerswerda, 02977, Germany

Location

Gemeinschaftspraxis Dr. Kolitsch

Katzhütte, 98746, Germany

Location

Praxis Dr. Gräßler

Pirna, 01796, Germany

Location

Praxis Bohl-Bühler

Potsdam, 14469, Germany

Location

Related Publications (3)

• 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.

  PMID: 15934081 BACKGROUND

• 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.

  PMID: 28619118 DERIVED

• 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.

  PMID: 26242443 DERIVED

MeSH Terms

Conditions

Spondylitis, Ankylosing; Spondylarthritis

Interventions

Diclofenac

Condition Hierarchy (Ancestors)

Axial Spondyloarthritis; Spondylarthropathies; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Ankylosis; Joint Diseases; Arthritis

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: July 14, 2008
• First Posted: July 15, 2008
• Study Start: September 1, 2008
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: August 25, 2014

Record last verified: 2014-08

Locations

DE (30)