Condition category
Musculoskeletal Diseases
Date applied
14/11/2019
Date assigned
23/01/2020
Last edited
24/01/2020
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting
Publication status
Results overdue

Plain English Summary

Background and study aims
Osteoarthritis is thought to be caused by mechanical damage to the tissues of the joints that results in breakdown of the cartilage layer that protects the ends of the bones and inflammation within the joint. This causes pain, swelling, stiffness and loss of mobility. Serum is the fluid left after blood has clotted. It contains proteins that are thought to reduce inflammation and encourage healing. This study aims to investigate whether injecting serum prepared from a person's own blood into their knee joint can reduce pain and improve mobility in knees affected by osteoarthritis.

Who can participate?
Adults aged 18 - 55 years who have mild osteoarthritis of the knee that is causing pain.

What does the study involve?
Participants will have samples of the fluid in their joint taken using a needle, one week before the start of treatment, before each of the two serum treatments and six months after treatment. These samples will be tested for levels of substances involved in inflammation. They will have two injections of the serum one week apart. The preparation of the serum will involve blood being taken. They will be asked about their pain, mobility and the impact of their knee problems at the pre-treatment visits, the two treatment visits and six months after treatment at the follow-up visit.

What are the possible benefits and risks of participating?
The treatment is free of charge. All participants will receive the treatment. Participants might benefit from a reduction in inflammation and pain.
The serum is prepared from the participant's own blood in a sterile and enclosed system, which means there is no risk of infection or immune reactions. As with any procedure involving injections, there may be some discomfort, pain or redness. There is a small risk of inflammation or infection around the injection site. The post-injection discomfort is expected to cease within three to four days.

Where is the study run from?
OrthoSera (Hungary). This is the company that makes the device used to prepare the serum.

When is the study starting and how long is it expected to run for?
February 2016 to April 2018

Who is funding the study?
OrthoSera (Hungary)

Who is the main contact?
Dr Eszter Fodor, eszterfodormd@gmail.com

Trial website

Contact information

Type

Scientific

Primary contact

Dr Eszter Fodor

ORCID ID

http://orcid.org/0000-0002-9487-2824

Contact details

Kikelet utca 35/C
Budapest
1125
Hungary
+36306640494
eszterfodormd@gmail.com

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

20160201

Study information

Scientific title

Evaluation of the synovial fluid inflammatory markers in the use of serum fraction of autologous platelet-rich fibrin, hyaluronic acid and their combination in the arthrosis of the knee joint

Acronym

ASPRF2016

Study hypothesis

1. Intraarticular injection of hyperacute serum decreases the concentration of inflammatory cytokines and matrix metalloproteinases presented in the osteoarthritic synovial fluid
2. Hyperacute serum injection has a beneficial effect on the level of pain and mobility of osteoarthritic patients

Ethics approval

Approved 12/07/2016, Scientific and Research Ethics Committee of the Hungarian Health Science Council (051 Budapest, Arany J. u. 6-8; +361476 1100; igazgatas@oth.antsz.hu), ref: 6906/2017/EKU

Study design

Single-centre open-label randomized study

Primary study design

Interventional

Secondary study design

Randomised parallel trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet. The PIS is available in Hungarian language.

Condition

Osteoarthritis

Intervention

Before treatment, samples of synovial fluid are taken from the patient's affected knee and levels of 40 proteins are measured. This can be done if there is at least 1 ml of synovial fluid in the joint. The orthopedic surgeon extracts the fluid from the joint using a needle.
All participants receive injections of autologous hyperacute serum produced using OrthoSera's device at 1 and 2 weeks after the synovial fluid sampling. 18 ml of blood (without anticoagulant) is taken from the right or left forearm vein of the patient using a butterfly needle set into the hypACT Inject Auto medical device. The SPRF fraction (hyperacute serum) is isolated using this device in a closed system by centrifugation. After centrifugation, the serum can be refrigerated and injected to the patient’s knee up to a week later or it can be injected immediately. It is transferred into a standard 5 ml syringe ready for injection into the affected knee joint.

Pain, mobility and the patient's opinion of their knee problems are assessed at baseline, after treatment at weeks 1 and 2, and at 6 months follow-up. Additional synovial fluid samples are taken at weeks 1 or 2 and at 6 months.

Intervention type

Biological/Vaccine

Phase

Not Specified

Drug names

Autologous hyperacute serum

Primary outcome measure

Markers of inflammation in synovial fluid measured using multiplex protein array (Luminex) technology at baseline, weeks 1 and 2, and month 6

Secondary outcome measures

1. Knee joint pain assessed using a Visual Analogue Scale (VAS) at baseline, week 1, week 2, and month 6
2. Knee joint mobility assessed using the Lysholm scale at baseline, week 1, week 2, and month 6
3. Patient's assessment of the impact of their knee impairment assessed using the Knee Injury and Osteoarthritis Outcome Score (KOOS) at baseline, week 1, week 2, and month 6

Overall trial start date

01/02/2016

Overall trial end date

01/04/2018

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Early or mild arthrosis of the knee joint that complies with Kellgren-Lawrence Grade 2 or 3 on standing anteroposterior (AP) weight-bearing X-ray during the last 3 months before the enrolment. If the patient does not have a proper X-ray from the last 3 months and indicates that he/she intends to participate in the study, a current X-ray is taken and the diagnosis is made by an orthopaedic surgeon or a radiologist.
2. Aged 18 - 55 years
3. Pain indicated by the patient is at least 40 on a 0 to 100 VAS scale during the last 3 months before the enrolment and the pain is related to the arthrosis
4. Clinical assessment that the pain is caused by the arthrosis
5. Inflammatory arthropathy is not included in the medical history or it is not suspected during the assessment
6. If the patient has a liver or kidney failure, then stable condition within the last 6 months should be confirmed

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

27

Total final enrolment

27

Participant exclusion criteria

1. Obesity (BMI >40 kg/m²)
2. Poorly controlled diabetes (HbA1C >7.5 or fasting glucose >11.11 mmol/l in the last 6 months
3. Surgery or injury of the other knee within 6 months or corticosteroid injection within 3 months
4. Inflammatory arthropathy in the medical history (e.g. rheumatoid arthritis, systemic lupus erythematosus involving the knee joint)
5. Diagnosis of any kind of rheumatoid arthritis or gout
6. Acute infection of the involved joint or in the surroundings, or untreated active infection or inflammation in any location
7. Moderate or severe anaemia (haemoglobin <11 g/dl) or thrombocytopenia (platelets <100,000/μl), conditions with haemoglobin >17 g/dl or <11 g/dl and/or platelets >500,000/μl or <100,000 /μl
8. Dialysis or liver failure, or untreated kidney or liver failure. Patients with chronic liver or kidney failure may be enrolled if they can demonstrate that their disease has been stabilized in the last 6 months
9. Patients receiving therapeutic dose of anticoagulants (e.g. warfarin, dabigatran, enoxaparin) or patients with coagulopathy in their medical history should be excluded. Patients receiving platelet aggregation inhibitors (e.g. aspirin, clopidogrel) should not be excluded, in accordance with the clinical practice
10. Pregnant or breastfeeding. A pregnancy test with negative result should be performed on female patients with childbearing potential and they should declare that they are not breast-feeding
11. Alcohol or drug abuse
12. Uncontrolled psychiatric disorder
13. Lack of travel options (e.g. to the follow-up examinations and back) or cooperation during the visits/participation in all visits
14. Progressive or acute malignant disease
15. Haematopoietic diseases (e.g. sickle cell anaemia)
16. Population at risk: patients unable to make decisions independently about signing up for the trial, or those under external influence

Recruitment start date

01/09/2016

Recruitment end date

01/01/2017

Locations

Countries of recruitment

Hungary

Trial participating centre

Kastélypark Klinika [Castle Park Clinic]
Hajdú street. 17
Tata
2890
Hungary

Sponsor information

Organisation

OrthoSera Kft.

Sponsor details

Borbála Lépcső 2
Budapest
1121
Hungary
+36 305249554
zsombor.lacza@orthosera.com

Sponsor type

Industry

Website

http://www.orthosera.com

Funders

Funder type

Industry

Funder name

OrthoSera Kft.

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

The results will be submitted to a peer-reviewed journal in 2020.

IPD sharing statement:
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

01/02/2020

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

24/01/2020: Internal review. 15/11/2019: Trial's existence confirmed by Egészségügyi Tudományos Tanács Tudományos és Kutatásetikai Bizottság [Hungarian Health Science Council Scientific and Research Ethics Committee].