UMIN-CTR Clinical Trial

Public title

Open labeled clinical research on utility of pentosan polysulfate(pentosan) to osteoarthritis of the knee

Acronym

Clinical research on utility of pentosan to knee OA

Scientific Title

Open labeled clinical research on utility of pentosan polysulfate(pentosan) to osteoarthritis of the knee

Scientific Title:Acronym

Clinical research on utility of pentosan to knee OA

Region

Japan

Condition

almost healthy with mild osteoarthritis of the knee

Classification by specialty

Clinical immunology

Orthopedics

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

Pentosan Polysulphate Sodium (pentosan) is used worldwide, either by injection in the muscle or by oral administration, as an OA treatment for dogs and racehorses. From the results of previous in vitro and animal model studies, we have proposed that the spectrum of pharmacological activities exhibited by pentosan would qualify it as DMOADs. The aim of this study is to assess the clinical effectiveness, functional outcome, safety, and patient satisfaction of a series of subcutaneous injections of NaPPS in patients with symptomatic primary OA of the knee.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

All patients were prospectively reviewed at entry and at weeks 1, 2, 3, 4, 8, 12, 16, 24, and 52 with a physical examination of the knee and VAS for stiffness, pain at rest or at walking, with ROM exercises, and with walking up and down stairs. The primary outcome variable in the knee pain was measured by VAS at each visit.
Blood and urine were checked including usual biochemical test and coagulation test.
Weight bearing radiographs were reviewed at the baseline and at the end of study to grade the degree of OA.

Key secondary outcomes

To check the change of the metabolism in the cartilage, procollagen new synthesis (CPII) and degradation of type II Collagen (C2C) in the blood was measured with an ELISA kit, in accordance with the manufacturer's instructions, and, in addition,WOMAC 3.1 (Likert) was used to measure secondary effectiveness (pain, stiffness, physical function, social function, emotional function).

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -but assessor(s) are blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

As a utilized agents, Pentosanpolysulfat SP 54, used in this study, was manufactured and supplied in sterile injectable vials (pentosan 100mg/ml) by bene-Arzneimittel GmbH, Munich, Germany.
The treatment consisted of 6 weekly subcutaneous injections (subcutaneous injection) of pentosan(2mg/kg), following the two weeks of test injections (the first was 25mg, second was 50mg).

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

40

years-old

<=

Age-upper limit

85

years-old

>=

Gender

Male and Female

Key inclusion criteria

Symptomatic patients with primary OA of the knee affecting the tibio-femoral and/or the patello-femoral compartment were consulted by senior orthopaedic surgeons who discussed their preferred management strategy. The radiographic indications of OA were grades 1 to 2 in Koshino's classification and stages 1 to 3a in the Hokkaido University stage grading system, changing into the Kellgren-Lawrence Grading System for OA, 1957, grades 1 to 2.

Key exclusion criteria

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 (besides aspirin) having gastric or duodenal ulcer or with suspicion of alimentary tract bleeding.
5. Patients who had other severe disease or handicap (for example (i.e.), 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, the patients were not eliminated if they could have a two-week wash-out period before entering into this study.

Target sample size

20

Name of lead principal investigator

1st name
Middle name
Last name	Hiroyuki Shindo, M.D., PhD

Organization

Nagasaki University Hospital

Division name

Orthopedic Surgery

Zip code

Address

1-7-1, Sakamoto, Nagasaki-city, Nagasaki, 852-8501, Japan

TEL

095-819-7321

Email

Name of contact person

1st name
Middle name
Last name	Kenji Kumagai, M.D., PhD

Organization

Nagasaki University Hospital

Division name

Orthopedic Surgery

Zip code

Address

1-7-1, Sakamoto, Nagasaki-city, Nagasaki, 852-8501, Japan

TEL

095-819-7321

Homepage URL

Email

kenjikum@nagasaki-u.ac.jp

Institute

Pentosan Research Society

Institute

Department

Personal name

Organization

None

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

長崎大学病院（長崎県）
Nagasaki University Hospital (Nagasaki Prefecture)

Date of disclosure of the study information

2009

Year

11

Month

22

Day

URL releasing protocol

Publication of results

Partially published

URL related to results and publications

Number of participants that the trial has enrolled

Results

The dose of this pentosan affected the blood coagulation tests, but the value in the study was within a safe range. A tiny abnormal finding was noted in serum chemistry: i.e., serum triglyceride at one hour after injection, but it was reduced quickly in the follow-up period.
The hydroarthroses were reduced quickly in all cases.
The ROM of the knee joint improved significantly. The clinical assessments, i.e., knee flexion, pain at walking, pain just after a climb up and down stairs, pain just after ROM exercise all improved significantly. The concentration of C2C in the blood decreased significantly.
The clinical benefits of this study continued for almost one year.
There was a statistically significant improvement from the baseline score in knee pain as measured by VAS at the 11th, 15th, 24th, and 52nd weeks.
These good results were thought to be due to the improvement of cartilage metabolism, synovium condition and anti-inflammatory function by pentosan.

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2005

Year

09

Month

05

Day

Date of IRB

Anticipated trial start date

2005

Year

12

Month

01

Day

Last follow-up date

2007

Year

08

Month

01

Day

Date of closure to data entry

2007

Year

09

Month

01

Day

Date trial data considered complete

2007

Year

09

Month

01

Day

Date analysis concluded

2009

Year

08

Month

01

Day

Other related information

Registered date

2009

Year

11

Month

22

Day

Last modified on

2009

Year

11

Month

22

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000003393