|- candidate number||2850|
|- NTR Number||NTR1111|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||5-nov-2007|
|- Secondary IDs||DKOA21 Reumacentrum Sint Maartenskliniek|
|- Public Title||Placebo gecontroleerd onderzoek naar het effect van 6 maanden behandeling met doxycycline op pijn en functie in patiŽnten met artrose van de knie.|
|- Scientific Title||Placebo controlled trial to evaluate the effect on pain and function of six months treatment with doxycycline in established knee osteoarthritis.|
|- hypothesis||Null hypothesis: OMERACT response percentages will not differ in patients with symptomatic and radiographic knee osteoarthritis treated with doxycycline 2dd100 mg during 24 weeks compared to placebo. |
|- Healt Condition(s) or Problem(s) studied|
|- Inclusion criteria||Inclusion criteria: |
1. Knee OA (index knee) according to the 1986 proposed ACR classification tree using clinical and radiological criteria (18): knee pain (VAS > 40mm during > 50% of last month), the presence of osteophytes and one of the following: age >50, crepitus, or morning stiffness < 30 minutes;
2. Kellgren Lawrence score II or III;
3. Criteria for mild to severe pain (KOOS pain sumscore question 5 to 9 > 100 in the index knee) must be fulfilled (19);
4. Ability to read and communicate well in Dutch.
|- Exclusion criteria||Exclusion criteria:|
1. Other rheumatic diseases like rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematodes or psoriatic arthritis;
2. The presence of secondary OA including OA caused by orthopaedic problems (severe malalignment, trauma), ochronosis, acromegaly, calcium pyrophosphate deposition disease (CPPD), haemochromatosis;
3. Severe functional problems related to diseases other than OA (functional class ARA IV);
4. Cognitive deficits affecting the scoring processes;
5. Severe OA (Kellgren Lawrence score IV);
6. Ipsilateral hip prosthesis in situ;
7. Contraindications for doxycycline use like allergy for tetracyclines and prior adequate treatment with doxycycline (>100mg for > 6 weeks for OA);
8. Planned other major interventions within 24 weeks, including lower limb surgery and intensive multidisciplinary approaches;
9. Recent intra-articular hyaluronic acid or corticosteroid application (<3 months) or surgery (<1 year) in the index knee;
10. Recent participation in other study (< 3 months);
11. (planned) pregnancy or reproductive state without proper contraceptive method.
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-dec-2007|
|- planned closingdate||1-jun-2009|
|- Target number of participants||230|
|- Interventions||The intervention-group will receive 2dd100 mg doxycycline monohydrate during 24 weeks. The control group will receive 2dd placebo during 24 weeks. |
|- Primary outcome||Primary endpoint:|
Percentage of the patients achieving clinical response on pain and function, as defined by the OMERACT-OARSI set of responder criteria based on the KOOS dutch version - pain (sumscore question 5 to 9) and function sumscore question 1-17 Ė and VAS patient Global Assessment at week 24 compared between placebo and verum.
|- Secondary outcome||Secondary endpoints: |
1. The use of analgesics (mean dose of paracetamol and NSAIDs, normalized for maximal registered dose);
2. Quality of life measured using the SF-36;
3. Safety (adverse events graded according to the CTC criteria).
|- Trial web site||N/A|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES||Prof. dr. J.T. Dissel, van|
|- CONTACT for SCIENTIFIC QUERIES||Prof. dr. J.T. Dissel, van|
|- Sponsor/Initiator |
(Source(s) of Monetary or Material Support)
|- Brief summary||Knee osteoarthritis (Knee OA) is a prevalent chronic disease characterized by cartilage failure resulting in pain, stiffness and function loss. Symptomatic treatments for knee OA include medical treatment with analgesics (acetaminophen, NSAIDs), paramedical treatment including occupational and physical therapy, weight reduction, and eventually joint replacement. Although NSAIDs have been extensively studied and used for OA, there are some important drawbacks to consider: inefficacy and gastrointestinal and cardiovascular safety issues and possibly increased progression of knee OA. Therefore the search for a DMOAD with both symptomatic and structural effects has been intensified in recent years.
Doxycycline is a tetracycline class antibiotic agent. Besides being an antimicrobacterial agent, it is a metalloproteinase inhibitor and inhibits the collagenase that splices collagen type IX that is present in articular cartilage. Doxycycline has been studied in human OA in one clinical trial by Brandt et al. Although effect on structural change has been shown for doxycycline, whether it also modifies symptoms for osteoarthritis has not been established yet. Side effects were mild and drop-out due to side effects was rare (<5%).|
A possible beneficial effect of doxycycline on pain and function in knee OA would allow this drug to be introduced in the non-invasive treatment of knee OA for both symptomatic and structural benefit. Because doxycycline is not associated with the important adverse effects of NSAIDs like gastrointestinal and cardiovascular morbidity and mortality this could be of high clinical relevance. In addition, doxycycline can be expected to have a beneficial effect on cartilage compared to the possible deleterious effect of NSAIDs on cartilage.
Objective of the study:
To asses the short term effect on pain and function and the safety of doxycycline in patients with mild to severe pain due to established knee OA.
|- Main changes (audit trail)|
|- RECORD||5-nov-2007 - 25-mrt-2008|