A 2-year, European Multicentre Study to Describe, Validate, and Predict Phenotypes of Knee Osteoarthritis

Knee Osteoarthritis Clinical Trial

— APPROACH  

Official title:

A 2-year Multicentre, EU, Exploratory Study Without Therapeutic Benefit in Patients With Knee Osteoarthritis to Describe, Validate, and Predict Phenotypes of Knee Osteoarthritis by Use of Clinical, Imaging, and Biochemical (Bio)Markers.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03883568
• Other study ID #: APPROACH-OA-P01
• Status: Completed
• Start date: January 19, 2018
• Est. completion date: December 1, 2021

Study information

• Verified date: May 2022
• Source: UMC Utrecht
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Rationale: Despite a large and growing disease burden in osteoarthritis (OA), many pharmaceutical companies have abandoned OA drug development. This is mainly due to the lack of appropriate outcome measures that can robustly identify patients that can benefit from a specific therapy. Different phenotypes of OA may benefit from different types of treatment. Therefore, novel markers to identify selected phenotypes of osteoarthritis may encourage drug development.

Objective: To prospectively describe in detail pre-identified progressing phenotypes of patients with knee OA by use of conventional and novel clinical, imaging, and biochemical (bio)markers, and to validate and refine a predictive model for these (and new) progressing phenotypes based on these markers.

Study design: APPROACH is an exploratory, European, five-centre, 2-year prospective follow-up, cohort study, with extensive measurements. In this study patients are treated according to regular care by their own physician with no study related treatment prescribed. Study related diagnostic and/or monitoring procedures are applied to the patients.

Study population: Patients with tibiofemoral knee osteoarthritis, according to the clinical ACR classification criteria, pre-identified based on demographic (e.g. age), clinical (e.g. Pain NRS) and tissue structure (e.g. radiographic joint space width) parameters.

Main study parameters/endpoints: Joint tissue structure based on radiographs, MRI, and biochemical (bio)markers as well as symptoms (pain, function) and quality of life by questionnaires.

Secondary parameters: A multitude of (novel and conventional) clinical, imaging, and biochemical parameters related to osteoarthritis.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The participants will not have any direct benefit from their participation in this study other than that their OA is maximally diagnosed and followed in detail for up to 2 years (screening, baseline, 6 months, 12 months, 24 months).

Description:

Patients will stay in the hospital for 4-5 hours per visit (for screening about 30 min) for physical examination, blood draw, MRI scans, radiographs of knees and hands (only at baseline and 24 months), CT scan of the knee (only at baseline and 24 months), low radiation whole body CT scan (only at baseline and 24 months), HandScan (only at baseline and 24 months), motion analysis, and performance based tests. They will be asked to fill out questionnaires about knee, hand and hip osteoarthritis, and about general health and pain. The patient council in the consortium indicated that the load is acceptable. The patient council will be involved in the execution of the study. The assumed risk is minimal for an individual patient and minimal compared to the contribution to the development of knowledge of their disease. These risks include minimal events due to blood sampling itself (such as hematoma or localized bleeding), radiation exposure by radiographic imaging techniques (with a minimal increased healthcare risk), and exposure to MRI techniques (without known risks and without use of contrast agents).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 297
• Est. completion date: December 1, 2021
• Est. primary completion date: April 3, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Informed consent obtained.

2. Ambulatory (able to walk unassisted)

3. At least 18 years of age

4. Capable of understanding the study

5. Capable of writing and reading in local language

6. Predominantly tibiofemoral knee osteoarthritis and satisfy the clinical classification criteria of the American College of Rheumatology (ACR): Knee pain and three of the following criteria: over 50 years age, less than 30 minutes of morning stiffness, crepitus on active motion, bony tenderness, bony enlargement, or no palpable warmth.

7. Highest probability to progress based on the algorithm based on the following parameters:

• Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire

• BMI (in recording height and weight)

• Pain NRS of the index knee at the moment of the screening visit

• Pain NRS of the index knee during the last week before the screening visit

• Age

• Gender

• KIDA parameters of the index knee, based on standardized weight-bearing (KIDA) radiograph, measured < 3 months (patients with a Joint Space Width (JSW) < 2 mm of the index knee will not be included)

Exclusion Criteria:

8. Not being able to comply to the protocol

9. Participating in a trial with local therapeutic intervention for index knee OA (pharmaceutical or surgical) or systemic Disease Modifying OsteoArthritic Drugs (DMOADs) or potential DMOADs treatments for OA at the same time or within the past 6 months or anticipated in the forthcoming; participation in non-interventional registries or epidemiological studies is allowed.

10. Surgery of the index knee in the past 6 months (to avoid interferences with imaging)

11. Scheduled or expected surgery of the index knee in the next 2 years (to avoid interferences with imaging)

12. Pregnancy (child bearing woman) because of imaging (radiation and MRI, risks)

13. Predominantly patellar femoral knee OA (clinical judgment)

14. The following secondary osteoarthritis of the knee: clinically significant deformities of the lower limbs (varus >10°, valgus >10°), septic arthritis, inflammatory joint disease, gout, major chondrocalcinosis (pseudogout), Paget's disease of the bone, ochronosis, acromegaly, haemochromatosis, Wilson's disease, rheumatic symptoms due to malignancies, primary osteochondromatosis, osteonecrosis, osteochondritis dissecans, haemophilia

15. Generalized pain syndrome, for example fibromyalgia

16. Patients with contra indication to MRI or CT

17. Hip replacement or expected hip replacement within 6 months

18. Osteosynthesis material near the knee joint

19. Self-reported severe Intervertebral disc (IVD) degeneration or facet OA

Related Conditions & MeSH terms

• Knee Osteoarthritis
• Osteoarthritis
• Osteoarthritis, Knee

Locations

Country	Name	City	State
France	Saint-Antoine hospital, AP-HP	Paris
Netherlands	Leiden University Medical Center	Leiden
Netherlands	UMC Utrecht	Utrecht
Norway	Diakonhjemmet hospital	Oslo
Spain	SERGAS	A Coruña

Sponsors (11)

Lead Sponsor	Collaborator
F.P.J.G. Lafeber	Assistance Publique - Hôpitaux de Paris, Complexo Hospitalario Universitario de A Coruña, Diakonhjemmet Hospital, GlaxoSmithKline, Institut de Recherches Internationales Servier, Leiden University Medical Center, Merck KGaA, Darmstadt, Germany, Newcastle University, Nordic Bioscience A/S, University of Surrey

Countries where clinical trial is conducted

France,  Netherlands,  Norway,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	OA structural progression of the index knee	radiographic joint space width in mm	over two years
Primary	OA pain progression of the index knee	increase in points in Knee Osteoarthritis Outcome Score for pain (0-100; 0 worst, 100 best condition)	over two years
Secondary	OA progression of the index knee	structural progression (e.g. cartilage volume on MRI in mm3)	over two years
Secondary	OA progression	structural progression (biochemical markers in units/ml in blood and urine)	over two years