Genicular Artery Embolisation for Knee Osteoarthritis II

NCT ID: NCT05423587

Last Updated: 2024-12-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

110 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-10-30

Study Completion Date

2028-06-30

Brief Summary

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This clinical study is designed as a double-blind sham controlled randomised trial with the option of sham group crossover to receive the GAE treatment at 6 months after unblinding. This study will determine if embolisation of abnormal neovasculature arising from branches of the genicular arteries reduces pain in patients with knee osteoarthritis. The study patient population will consist of up to 110 subjects with knee pain for at least 3 months that is resistant to conservative treatment measures. Subjects will be treated with knee embolisation or 2 mL of saline in the sham arm. At 6 months, all subjects in the sham arm will be allowed to cross-over and receive the embolisation procedure with a follow-up duration of 18 months. The total planned study duration is 3.5 years.

Detailed Description

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This is a single-center, randomised trial to compare patients who receive genicular artery embolisation of the knee with patients who receive a sham procedure with saline injection.

The study population will consist of up to 110 subjects with knee pain that is resistant to conservative treatment measures for at least 3 months. Subjects will be followed for 24 months. At 6 months patients will be unblinded and offered an optional crossover to receive the GAE procedure with 18 months follow-up.

Alongside a sham surgery placebo arm, a high-quality systematic review of surgical RCTs was used as a suitable benchmark to inform the sample size and power calculation.

With a 0-100 scale for the primary endpoint of KOOS4, assuming a 1:1 randomization, a mean difference of 6.4 (i.e., effect size) between GAE and Sham treatments, a common standard deviation of 10 (i.e., a Cohen's D of 0.64), an alpha error of 2-sided 0.05 and a power of 0.85, the 2-arm total sample size the requirement is 88 subjects (44 each arm) by Normal approximation. Allowing for a participant dropout rate of 20%, the enrolment goal is 110 participants, approximately 55 in each study arm.

All study subjects will undergo a physical exam and history, a contrast-enhanced knee MRI, blood serum and neuropschological assessment with a functional head MRI to identify potential predictors of treatment success.

In the GAE treatment arm subject will undergo a genicular artery embolization with Embozene microspheres (100 micron) (Varian Medical Systems) and the Sham group will receive saline through the transarterial catheter through groin access.

Participants will be randomly assigned to have particulate embolisation with 100-micron Embozene particles, or to injection with 2 ml heparinized normal saline (sham arm) At 6 months participants will be unblinded and there will be an open extension period for 6 months, in which participants in the sham arm will be offered GAE.

Follow-up visits will be at 1 month, 3 months, 6 months, 12 months and 24 months post randomisation. At these visits subjects will complete the KOOS score, the visual analog scale (VAS) pain score, an analgesia diary, and at specific time points the EQ-5D-3L, and report any new adverse events (AEs).All subjects will undergo a contrast-enhanced knee MRI at baseline and at 6 and 12 months.

At 6 months after unblinding the sham group subjects have the option to cross over and receive the GAE treatment with follow-up at 1 month, 3 months, 6 months, 12 months and 18 months.

Conditions

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Knee Osteoarthritis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Single Site, Double Blind Sham Randomized Controlled Trial with Sham subject optional crossover to the treatment arm (GAE) at 6 months post randomization to determine if embolization of abnormal blood vessels arising from branches of the genicular arteries reduces pain in patients with knee osteoarthritis.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Caregivers
A randomization algorithm (hidden and protected) allocates a random number to each of the 110 subjects. The outputs of this algorithm will only be accessible to those who are unrestricted by experimental blinding (operator, radiographer, scrub nurse). For safety reasons the interventional radiologist will be aware of the treatment arm (non-blind).

Study Groups

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GAE Treatment

The genicular artery embolisation procedure identifies abnormal blood vessels in the knee via angiogram imaging. Through groin access and puncture of the femoral artery through a small sheath tiny microspheres (Embozene(TM)) will be injected into this area and reduce blood flow in order to reduce pain.

Group Type EXPERIMENTAL

Genicular Artery Embolisation

Intervention Type PROCEDURE

Transarterial catheter directed embolisation of hypervascularity in patients with mild to moderate knee osteoarthritis

Sham Procedure

In the control (sham) arm patients will not undergo the embolisation procedure with microspheres, instead they will have 2ml of saline injected into their knee artery supplying the abnormal area of the knee. The remainder of the procedure is otherwise identical between the two groups.

Group Type SHAM_COMPARATOR

Genicular Artery Injection

Intervention Type PROCEDURE

Transarterial catheter directed injection of normal (0.9%) saline in patients with mild to moderate knee osteoarthritis

Interventions

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Genicular Artery Embolisation

Transarterial catheter directed embolisation of hypervascularity in patients with mild to moderate knee osteoarthritis

Intervention Type PROCEDURE

Genicular Artery Injection

Transarterial catheter directed injection of normal (0.9%) saline in patients with mild to moderate knee osteoarthritis

Intervention Type PROCEDURE

Other Intervention Names

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Embozene Microspheres Embozene

Eligibility Criteria

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Inclusion Criteria

* Participant is willing and able to give informed consent for participation in the study.
* Participants aged 45 years or above.
* Grade 1-3 knee OA on X-ray as per Kellgren-Lawrence Grading Scale
* Knee pain for at least 3 months resistant to conservative non-surgical treatment (e.g., physiotherapy, steroid injections, weight loss programs, PRP (platelet-rich plasma) injections)
* Be able to lie flat for at least 6 hours-this will be assessed by asking how participants sleep (bed, chair recumbent, semi-recumbent) and assessing what prevents them from lying flat overnight (breathlessness, back pain, etc)
* Minimum score of 50 on baseline 0 - 100 VAS

Exclusion Criteria

The patient may not enter the study if ANY of the following apply:

* Rheumatoid arthritis or infectious arthritis
* Severe knee OA (grade 4 on x-ray as per Kellgren-Lawrence Grade)
* Renal impairment: eGFR \<45. Assessed from medical records or a blood test if required as is part of standard clinical practice when considering a patient for a therapeutic intervention.
* Patients with a bleeding diathesis, or other bleeding risk such as patients on warfarin which cannot be stopped easily (e.g., patients with metallic heart valves) assessed by asking the patient and from medical records. Uncorrectable bleeding diathesis: INR\>1.6, Platelets \<50,000
* Requires oxygen on ambulation. Assessed by asking the patient and from medical records.
* Low life expectancy (\<1 year)
* Communication difficulty due to language barriers
* Contraindication to MRI
* Known allergies to barium sulfate, 3-aminopropyltrialkoxysilane, polyphosphazene or IV radiopaque contrast agent
* History of Peripheral Arterial Disease (PAD) with intermittent claudication and/or rest pain
* Pregnancy or positive pregnancy test (the participant will be exposed to ionising radiation during the fluoroscopy procedure)
* Any other significant disease or disorder which, in the opinion of the recruiting physician, may put the participants at risk because of participation in the study, or may influence the result of the study or the participant's ability to participate
Minimum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Varian, a Siemens Healthineers Company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mark W Little, MD

Role: PRINCIPAL_INVESTIGATOR

Royal Berkshire NHS Foundation Trust, Reading, UK

Locations

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Royal Berkshire NHS Foundation Trust

Reading, , United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Heike S Hausen, MD

Role: CONTACT

2068903102

Kate Pietrovito

Role: CONTACT

+19782908408

Facility Contacts

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Mark W Little, MD

Role: primary

01183225111

References

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Little MW, Harrison R, MacGill S, Speirs A, Briggs JH, Tayton E, Davies NLC, Hausen HS, McCann C, Levine LL, Sharma RA, Gibson M. Genicular Artery Embolisation in Patients with Osteoarthritis of the Knee (GENESIS 2): Protocol for a Double-Blind Randomised Sham-Controlled Trial. Cardiovasc Intervent Radiol. 2023 Sep;46(9):1276-1282. doi: 10.1007/s00270-023-03477-z. Epub 2023 Jun 19.

Reference Type DERIVED
PMID: 37337060 (View on PubMed)

Other Identifiers

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286849

Identifier Type: OTHER

Identifier Source: secondary_id

VAR-2021-11

Identifier Type: -

Identifier Source: org_study_id