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

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ClinicalTrials.gov Identifier: NCT00715091
Recruitment Status : Completed
First Posted : July 15, 2008
Last Update Posted : August 25, 2014
Sponsor:
Information provided by (Responsible Party):
J. Sieper, Charite University, Berlin, Germany

Tracking Information
First Submitted Date  ICMJE July 14, 2008
First Posted Date  ICMJE July 15, 2008
Last Update Posted Date August 25, 2014
Study Start Date  ICMJE September 2008
Actual Primary Completion Date December 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 14, 2008)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT00715091 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 14, 2008)
  • 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 ]
  • ITT analysis of radiographic change. [ Time Frame: 2 years ]
  • Change in VAS back pain, BASDAI, BASFI, BASMI, CRP. [ Time Frame: 2 years ]
  • event rates of serious and non-serious adverse events will be documented and compared between the two groups. [ Time Frame: 2 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effects of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) on RAdiographic Damage in Ankylosing Spondylitis
Official Title  ICMJE Effects of NSAIDs on RAdiographic Damage in Ankylosing Spondylitis (ENRADAS) - a Prospective Randomised Controlled Trial
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Ankylosing Spondylitis
Intervention  ICMJE
  • Drug: diclophenac
    continuous (daily) treatment of diclofenac cholestyramine 150 mg, divided into 75mg twice daily
    Other Name: voltaren resinat
  • Drug: diclophenac
    treatment on-demand (as needed) with diclofenac-cholestyramine 75 to 150 mg daily
    Other Name: Voltaren resinate
Study Arms  ICMJE
  • Experimental: 1
    continuous (daily) treatment with diclofenac cholestyramine 150 mg (Voltaren Resinate), divided into 75mg Voltaren twice daily
    Intervention: Drug: diclophenac
  • 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.
    Intervention: Drug: diclophenac
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 22, 2014)
180
Original Estimated Enrollment  ICMJE
 (submitted: July 14, 2008)
360
Actual Study Completion Date  ICMJE December 2013
Actual Primary Completion Date December 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00715091
Other Study ID Numbers  ICMJE ENRADAS-01
EUDA-CT: 2007-007637-39
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party J. Sieper, Charite University, Berlin, Germany
Study Sponsor  ICMJE Charite University, Berlin, Germany
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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
PRS Account Charite University, Berlin, Germany
Verification Date August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP