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Trial registered on ANZCTR


Registration number
ACTRN12619000047190
Ethics application status
Approved
Date submitted
10/01/2019
Date registered
14/01/2019
Date last updated
14/01/2019
Date data sharing statement initially provided
14/01/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Pentosan Polysulphate (PPS) for Dyslipidaemia in Knee Osteoarthritis
Scientific title
Pentosan Polysulphate (PPS) for Dyslipidaemia in Knee Osteoarthritis
Secondary ID [1] 297015 0
Nil
Universal Trial Number (UTN)
U1111-1226-4185
Trial acronym
PPS Study
Linked study record
Not Linked

Health condition
Health condition(s) or problem(s) studied:
Osteoarthritis 310994 0
Dyslipidaemia 310996 0
Condition category
Condition code
Musculoskeletal 309649 309649 0 0
Osteoarthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
100 mg oral Pentosan polysulphate Capsules calculated as per 10 mg per 1 Kg body weight.for e.g 5 capsules if weight =50-55 Kg, 6 capsules if weight=55-60 Kg
Capsules taken once every 4th day
Monitoring of the Intervention - Paper Diary and e diary through a mobile app (both Android and ios phones)
Intervention code [1] 313296 0
Treatment: Drugs
Comparator / control treatment
No Control Group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 318606 0
The primary outcome of interest is the change in serum triglycerides levels
Timepoint [1] 318606 0
Baseline, 16 weeks post baseline visit
Secondary outcome [1] 365515 0
Change from baseline in blood Cholesterol through serum assay
Timepoint [1] 365515 0
6, 26 weeks post baseline visit
Secondary outcome [2] 365517 0
Changes from baseline in Full blood counts (FBC)
Timepoint [2] 365517 0
6,16,26 weeks post baseline visit
Secondary outcome [3] 365518 0
Changes from baseline in Prothrombin time (PT) through plasma assay
Timepoint [3] 365518 0
6,16,26 weeks post baseline visit
Secondary outcome [4] 365519 0
Composite changes from baseline in Self-reported outcomes of pain, stiffness and functional status measured using the Knee Osteoarthritis Outcome Score (KOOS)
Timepoint [4] 365519 0
6,16,26 weeks post baseline visit
Secondary outcome [5] 365520 0
Changes from Baseline in Severity Knee Pain Score
Timepoint [5] 365520 0
6,16,26 weeks post baseline visit
Secondary outcome [6] 365521 0
Composite Changes from baseline in Sub-chondral bone structure,density, vascularity by MRI
Timepoint [6] 365521 0
26 weeks post baseline visit
Secondary outcome [7] 365576 0
Changes from baseline in Activated Partial thromboplastin time (APTT) through plasma assay
Timepoint [7] 365576 0
6,16,26 weeks post baseline visit
Secondary outcome [8] 365577 0
Changes from baseline in D-Dimer through plasma assay
Timepoint [8] 365577 0
6,16,26 weeks post baseline visit

Eligibility
Key inclusion criteria
A. Male or female patients minimum of 45 years or more;
B. Are able to give written informed consent and to participate fully in the interventions and follow-up procedures including travel to the Royal North Shore Hospital;
C. Have history of primary hypercholesterolemia and total fasting cholesterol above 5.0mmol/L at screening;
D. Have any symptoms associated with OA of the knee for at least 6 months prior to screening visit and confirmation of OA based on the clinical and radiological criteria of American College of Rheumatology Criteria for OA (Altman et al, 1986) of the knee prior or at screening.
E. Kellgren-Lawrence (K-L) Grade 2 or 3 in the index knee based on knee radiograph performed at screening or within six months of the screening visit;
F. Have Index knee pain on most days over the last month.
G. Knee Pain Severity Scale above 4 using an 11-point (0-10) numerical severity scale where 0 is no pain at all and 10 is worst possible pain in the last 48 hours at baseline visit;
(If both knees are affected by OA then the most symptomatic knee will be considered the index knee. If both knees are equally affected, the index knee will be determined by the Investigator.)
H. BMI<40 kg/m2 at screening visit;
I. Agree to maintain their usual activity level and diet throughout the study;
J. Female of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation;
Minimum age
45 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
A. Documented history of Fibromyalgia, Reiter’s syndrome, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or arthritis associated with inflammatory bowel disease;
B. Known hypersensitivity to Pentosan Polysulfate or related compounds (e.g. heparin);
C. Any unstable concurrent clinically significant acute, chronic medical conditions or abnormal laboratory findings that, in the judgment of the Investigator, would jeopardise the safety of the patient, interfere with the objectives of the protocol, or affect the patients compliance with the study requirements, as determined by the investigator;
D. Contraindications for MRI including but not limited to pacemaker, metal sutures, presence of shrapnel, or claustrophobia;
E. Current or a recent history (within last 12 months) of bleeding (a gastric or duodenal ulcer or suspicion of GI tract bleeding) or menorrhagia;
F. Haemophilia ;
G. Planned / anticipated invasive procedure (or surgery) within 6 months;
H. Recent surgery;
I. Bilateral Knee replacement
J. Concurrent heparin or oral anti-coagulant therapy;
K. Concurrent therapy with lipid –modifying drugs for hypercholesterolemia;
L. Female patients who are pregnant, nursing or intend to get pregnant;
M. Use of prohibited pain medication( see below)
• Oral non-steroidal anti-inflammatory drugs (NSAIDs)
• Aspirin (>325 mg per day)
• Centrally-acting pain medications (e.g., pregabalin, gabapentin, duloxetine)
• Opioids (e.g. tramadol)
• Topical therapies (e.g., NSAIDs ) applied to the index knee
• Muscle relaxants (e.g. tetrazepam, diazepam)
N. Prohibited Concomitant Medications:
• Lipid-modifying drugs: statins ( e.g. atorvastatin, pravastatin and simvastatin) or ezetimibe (Ezetrol)
• Anticoagulants including heparin, warfarin, apixaban (Eliquis), dabigatran (Pradaxa) and rivaroxaban (Xarelto)
• Biological/ disease –modifying anti-rheumatic drugs for arthritis
• Steroid drugs for systematic use

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Descriptive statistics of baseline characteristics will be provided; continuous variables will be summarised in terms of means and standard deviation (SD) where appropriate or median (range), categorical variables will be presented as frequency (percentage).
The baseline and 4-month serum triglyceride (TG) measurements will be summarised as mean and standard deviation. The change in serum TG between the baseline and 4-month assessment will be summarised as mean with corresponding 95% confidence intervals and assessed using a paired t-test.
Secondary outcomes will be summarised in terms of means and standard deviation at each time point and the change in outcome between baseline and follow-up assessments will be summarised in terms of mean (95% CI) and assessed using a paired t-test. To investigate the relationship between the change in lipid levels and change in clinical outcomes across assessments, general estimating equation (GEE) models will be used including time, clinical outcome and adjusting for baseline lipid level.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 12846 0
Royal North Shore Hospital - St Leonards
Recruitment postcode(s) [1] 25321 0
2065 - St Leonards

Funding & Sponsors
Funding source category [1] 301584 0
Commercial sector/Industry
Name [1] 301584 0
Sylvan Scientific Pty Ltd
Address [1] 301584 0
ABN 26 112 022 849
109-111 Bronte Road, Bondi Junction,
New South Wales, 2022,
AUSTRALIA
Country [1] 301584 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
F 23, Administration building, Corner of the eastern Avenue and the city road
Camperdown, NSW 2006
Country
Australia
Secondary sponsor category [1] 301281 0
None
Name [1] 301281 0
Address [1] 301281 0
Country [1] 301281 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302313 0
Northern Sydney Local Health District Human Research Ethics Committee (EC00112)
Ethics committee address [1] 302313 0
Research Office
Kolling Building, Level 13
Royal North Shore Hospital
St Leonards
NSW 2065
Tel (02) 9926 4590
Fax (02) 9926 6179
Ethics committee country [1] 302313 0
Australia
Date submitted for ethics approval [1] 302313 0
01/03/2018
Approval date [1] 302313 0
28/06/2018
Ethics approval number [1] 302313 0
HREC/18/HAWKE/73

Summary
Brief summary
This study aims to determine whether oral delivery of PPS drug will lower lipid levels in patients with knee OA. We are also interested to investigate if the improvement in dyslipidaemia might lead to improving OA symptoms and slowing disease progression, as measured by function, pain and MRI, in patients with mild to moderate knee osteoarthritis.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 89786 0
Prof David Hunter
Address 89786 0
Department of Rheumatology,
Clinical Administration 7 C
Royal North Shore Hospital
St. Leonards, NSW 2065
Country 89786 0
Australia
Phone 89786 0
+61 2 9463 1887
Fax 89786 0
+61 2 9463 1077
Email 89786 0
david.hunter@sydney.edu.au
Contact person for public queries
Name 89787 0
Ms Sonika Virk
Address 89787 0
Department of Rheumatology,
Clinical Administration 7 C
Royal North Shore Hospital
St. Leonards, NSW 2065
Country 89787 0
Australia
Phone 89787 0
+61 2 9926 7821
Fax 89787 0
+61 2 9463 1077
Email 89787 0
sonika.virk@sydney.edu.au
Contact person for scientific queries
Name 89788 0
Prof David Hunter
Address 89788 0
Department of Rheumatology,
Clinical Administration 7 C
Royal North Shore Hospital
St. Leonards, NSW 2065
Country 89788 0
Australia
Phone 89788 0
+61 2 9463 1887
Fax 89788 0
Email 89788 0
david.hunter@sydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
No Results