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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
J. Sieper, Charite University, Berlin, Germany
ClinicalTrials.gov Identifier:
NCT00715091
First received: July 14, 2008
Last updated: August 22, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Ankylosing Spondylitis
Drug: diclophenac
Phase 4

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:


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 ]

Enrollment: 180
Study Start Date: September 2008
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
continuous (daily) treatment 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) 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 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
Germany
Praxis Dr. Jacki
Tübingen, Baden-Württemberg, Germany, 72072
Medizinische Universitätsklinik Innere Medizin
Tübingen, Baden-Württemberg, Germany, 1072076
Praxis Dr. Manger
Bamberg, Bayern, Germany, 96047
Praxis Dr. Ochs
Bayreuth, Bayern, Germany, 95445
Praxis Dr. Kellner
München, Bayern, Germany, 80639
Praxiszentrum St. Bonifazius
München, Bayern, Germany, 81541
Gemeinschaftspraxis Dr. Göttl
Passau, Bayern, Germany, 94032
Fachklinik Bad Bentheim
Bad Bentheim, Niedersachsen, Germany, 48455
Praxis Dr. Rockwitz
Goslar, Niedersachsen, Germany, 38640
Gemeinschaftspraxis Dr. von Hinüber
Hildesheim, Niedersachsen, Germany, 31134
Gemeinschaftspraxis Dr. Gauler
Osnabrück, Niedersachsen, Germany, 49076
Praxis Dr. Dockhorn
Weener, Niedersachsen, Germany, 26828
Rheumatologische Schwerpunktpraxis
Düsseldorf, Nordrhein-Westfalen, Germany, 40217
Universitätsklinikum DüsseldorfKlink für Endokrinologie, Diabetologie und Rheumatologie
Düsseldorf, Nordrhein-Westfalen, Germany, 40001
Evangelisches Krankenhaus
Ratingen, Nordrhein-Westfalen, Germany, 40882
Praxis Dr. Kramer
Remscheid, Nordrhein-Westfalen, Germany, 42897
Praxis Dr. Schoo
Rheine, Nordrhein-Westfalen, Germany, 48431
Rheumatologische Praxis Dr. Spieler
Zerbst, Sachsen-Anhalt, Germany, 39261
Brandt
Berlin, Germany, 12163
Praxis Mielke
Berlin, Germany, 12627
Praxis Zinke
Berlin, Germany, 13055
Gemeinschaftspraxis Dr. Schwenke
Dresden, Germany, 01109
Praxis Dr. Pick
Grafschaft bei Bad Neuenahr-Ahrweiler, Germany, 53501
Praxis Dr. Kühne
Haldensleben, Germany, 39340
St. Josefs-Krankenhaus, Rheumatologie
Herne, Germany, 44652
Rheumazentrum Ruhrgebiet, St. Josefs Krankenhaus
Herne, Germany, 44652
Praxis Dr. Kapelle
Hoyerswerda, Germany, 02977
Gemeinschaftspraxis Dr. Kolitsch
Katzhütte, Germany, 98746
Praxis Dr. Gräßler
Pirna, Germany, 01796
Praxis Bohl-Bühler
Potsdam, Germany, 14469
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:
Publications:
Responsible Party: J. Sieper, Prof., 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: August 22, 2014
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
Ankylosis
Arthritis
Bone Diseases
Bone Diseases, Infectious
Infection
Joint Diseases
Musculoskeletal Diseases
Spinal Diseases
Spondylarthritis
Spondylarthropathies
Anti-Inflammatory Agents, Non-Steroidal
Cholestyramine Resin
Diclofenac
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anticholesteremic Agents
Antimetabolites
Antirheumatic Agents
Central Nervous System Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014