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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


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
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