Sodium Pentosan Polysulfate Resulted in Cartilage Improvement in Knee Osteoarthritis - An Open Clinical Trial

Kenji Kumagai; Susumu Shirabe; Noriaki Miyata; Masakazu Murata; Atsushi Yamauchi; Yasuhumi Kataoka; Masami Niwa

Disclosures

BMC Clin Pharmacol. 2010;10:1-24. 

In This Article

Methods

1. Study Design

The clinical study was designed as a single-center, open-label trial with an 8-week treatment phase. The radiographic indications of OA were mild to moderate OA, as described below. The follow-up continued for twelve months.

2. Patient Recruitment

Symptomatic patients with primary OA of the knee were consulted by senior orthopedic surgeons who discussed their preferred management strategy. The radiographic indications of OA were grades 1 to 3 using the Kellgren-Lawrence Grading System (K/L grade).[2] The elimination of patients was carried out according to the following:

  1. Patients who received previous intra-articular corticosteroid or another drug injection in the knee joint within the previous 3 months.

  2. Patients who had other lower-extremity musculoskeletal disability or pain

  3. Patients who had pain exceeding 45 mm on a 100-mm visual analogue scale (VAS, 0- 100, 100 as worst pain) immediately following walking for 50 m.

  4. Patients who had any bleeding tendency with anti-coagulant drugs (aspirin by way of exception) having gastric or duodenal ulcer or with suspicion of alimentary tract bleeding.

  5. Patients who had other severe disease or handicap (for example, diseases involving the liver, kidney, and bone marrow)

  6. Patients who had a past history of drug allergy

  7. Patients who were pregnant or were breastfeeding

  8. Patients who had difficulty providing us with information

  9. Patients who had difficulty with the informed consent

About using NSAIDs, patients were not eliminated if they underwent a two-week wash-out period before entering into this study.

According to the above conditions, twenty patients with knee OA were recruited.

The patient characteristics were as follows:

The average age was 63 years (from 35 to 80). All cases were female. Eight cases had right knee OA, 12 had left knee OA. The classifications of the weight bearing radiographs in K/L grade were grade 2 in 18 cases, and grade 3 in 2 cases. The average WOMAC score at the first visit was 37.0 (from 18 to 70).

3. Utilized Agents

Pentosan polysulfate SP 54, used as pentosan in this study, was manufactured and supplied in sterile injectable vials (100mg/ml) by bene-Arzneimittel GmbH, Munich, Germany. It was illegal to use pentosan in Japan according to the relevant Japanese laws. So the study was approved by the review board of the Graduate School of Biomedical Sciences, Nagasaki University.

4. Study Methods

Following consent, the treatment consisted of 6 weekly subcutaneous injections (sc) of pentosan (2mg/kg), following the two weeks of test injections (the first was 25mg, the second was 50mg).

No aspiration was performed, even if synovial fluid was present in the knee. After the initial phase, all patients were advised to avoid NSAIDs for 52 weeks. Paracetamol (<2000 mg/day) was allowed for break-through pain. All patients were allowed to maintain standard physical therapy.

5. Outcome Assessment

All patients were prospectively reviewed at entry and at weeks 1, 2, 3, 4, 8, 12, 16, 24, and 52 with initial question of pain at rest and walking, a physical examination of the knee and VAS for pain with ROM exercises, 50m walking, walking up and down stairs, or at 10 minutes rest after exercises. To check the change of the metabolism in the cartilage, degradation of type II collagen (C2C) in the blood was measured with a commercial ELISA kit, in addition to the usual biochemical tests. Weight bearing radiographs were reviewed at baseline and at the end of study to grade the degree of OA using K/L grade. WOMAC 3.1 (Likert) was used to measure secondary effectiveness.

6. Adverse Events

Safety was assessed at each visit. Pentosan is a heparin-like agent and is not used in Japan. Activated clotting time (ACT) is a measure of the anticoagulation affects of heparin. So we checked the level of ACT, as well as the usual blood coagulation test one hour after every injection. All adverse events (AE), however minor, were recorded.

7. Statistics

All data was handled by members who did not treat or check the patients. The data was compared between the entry point and each of the follow-up points. The statistical significance, compared with the value at entry, was determined by one-way analysis of variance ( ANOVA ) and Dunnett's method. A p value of < 0.05 was considered significant for all statistical tests. Comparison of data was performed on a personal computer using StatView for Windows, ver. 5.0.1; SAS Institute Inc, Cary, NC, U.S.A.

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