Safety and Efficacy of a Lipiodol Emulsion for the Embolization of Hypervascularizations in Patients With Knee Pain (LipioJoint1) (LipioJoint1)

Prospective Study of the Safety and Efficacy of the Use of a Lipiodol Emulsion for the Embolization of Inflammatory Hypervascularizations Observed in Patients With Joint or Abarticular Knee Pain

Knee osteoarthritis is a common cause of disability in patients who are often young and active. Surgery being an option only for the most severe cases, there is little alternative in case of failure of recommended medication. Inflammatory hypervascularization of the joint is a known source of pain. Temporary embolization of intra-arterial inflammatory hypervascularization has been used since 2012 with good results on pain relief to treat patients with musculoskeletal disorders that are resistant to conventional treatments. Lipiodol® has transient embolizing properties when in emulsion with a contrast agent. It has been used as an emulsion with chemotherapy for the treatment of metastases and primary intra-arterial liver cancer (chemo-embolization) for many years without serious side effects. We hypothesized that Lipiodol® in emulsion could serve as a temporary embolization agent for the treatment of inflammatory hypervascularization responsible for musculoskeletal disorders in humans.

Study Overview

• Status: Completed
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Drug: Lipiodol

Detailed Description

It is a Phase 1, Single-Arm, Open-label, Multicenter Interventional Prospective Study.

In order to ensure the best possible patient safety, a sequential inclusion of the first 6 patients is planned. Thus, the inclusion of each subsequent patient (patient 2-6) will only be considered after reviewing previously included patient safety data. Safety data after the inclusion of each patient (after a step-back of at least one week), as well as the cumulative review of previously included patient safety data, will be brought to the attention of all investigators involved in this research.

In addition, the following information will be transmitted to the Competent Authority without delay:

• a review of the safety and efficacy of the first 3 patients included with a step back for the last patient of at least one week after the administration of the experimental drug, as well as an argument as to the continuation of this research with regard to these data, with a discussion of the risks incurred in relation to the expected profit
• a review of the safety and effectiveness of the first 3 patients after the inclusion of the first 6 patients, as well as an argument as to the continuation of this research with regard to these data, with a discussion of the risks incurred compared to the expected benefit.

The patients will be embolized by the Interventional Radiology Department of the European Hospital Georges Pompidou (HEGP). Embolization will be performed by an experienced radiologist during a conventional hospitalization or a day hospitalization. A clinical follow-up will be carried out at 1 week, 1 month and 3 months after embolization by clinics and patient self-assessment (WOMAC, SF-36).

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015
    • Hôpital Europeen Georges Pompidou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 31 years to 86 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of primary inflammatory knee osteoarthritis of the target joint defined by a knee osteoarthritis according to the American College of Rheumatology (ACR) classification and a score ≥ 2 according to the classification of Kellgren and Lawrence
• Patient not eligible for surgery (or refusing surgery)
• Analog Visual Scale (VAS) pain ≥ 40 mm despite analgesic treatment for at least 3 months
• Failure or intolerance of treatment with NSAIDs and/or tramadol and/or acetaminophen, and/or failure or intolerance or patient refusing strong opioids medication (morphine, codeine)
• Failure or patient refusal of corticosteroid infiltration
• Patient who has signed an informed consent

Exclusion Criteria:

• Patient who is unable or unable to comply with the follow-up schedule
• Infiltration of target joint less than three months old
• Treated hyperthyroidism
• Traumatic injury, hemorrhage or bleeding less than 1 week old in the target joint
• Known arterial disease of the lower limbs stage ≥ 2 according to the classification of Leriche and Fontaine
• Known severe allergy to Lipiodol® and/or iodized contrast product
• Known severe kidney failure (creatinine clearance < 30 ml/min)
• Pregnant or breastfeeding woman
• Patient not affiliated with a French Medicare
• Patient benefiting from legal protection
• Participation in another interventional research

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Embolization; Embolization of the inflammatory hypervascularization with a lipiodol emulsion	Drug: Lipiodol; Lipiodol in emulsion with contrast agent; Other Names: Optiray

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serious Adverse Events (SAE)	Number of SAE related to Embolization	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immediate Technical success	Success of catheterization and embolization of target hypervascularization	Intraoperative
Pain improvement 1 week after embolization	Analog Visual Scale score (0-100) comparison to baseline VAS score is determined by measuring in millimetres from the left hand end of the line to the point that the patients marks. The Scale is rated from 0 to 100 (no pain to extremely severe pain)	1 week
Pain improvement 1 month after embolization	Analog Visual Scale score (0-100) comparison to baseline VAS score is determined by measuring in millimetres from the left hand end of the line to the point that the patients marks. The Scale is rated from 0 to 100 (no pain to extremely severe pain)	1 month
Pain improvement 3 month after embolization	Analog Visual Scale score (0-100) comparison to baseline VAS score is determined by measuring in millimetres from the left hand end of the line to the point that the patients marks. The Scale is rated from 0 to 100 (no pain to extremely severe pain)	3 months
Articular impotence improvement 1 week after embolization	Western Ontario and McMaster Universities Osteoarthritis Index score (0-96) comparison to baseline	1 week
Articular impotence improvement 1 month after embolization	Western Ontario and McMaster Universities Osteoarthritis Index score (0-96) comparison to baseline	1 month
Articular impotence improvement 3 month after embolization	Western Ontario and McMaster Universities Osteoarthritis Index score (0-96) comparison to baseline	3 months
Quality of life improvement 3 month after embolization	Short Form Health Survey (SF-36) score comparison to baseline SF-36 consists of eight scaled scores which are the weighted sums of the questions in their section, a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.	3 months
Pain medication improvement 1 week after embolization	Dose of analgesic medication compared to baseline (mg/24h)	1 week
Pain medication improvement 1 month after embolization	Dose of analgesic medication compared to baseline (mg/24h)	1 month
Pain medication improvement 3 month after embolization	Dose of analgesic medication compared to baseline (mg/24h)	3 months
Patient's satisfaction	Patient's satisfaction questionnaire : qualitative questionnaire with 5 ordered modalities (0 = no to 4 = yes)	3 months
Adverse Events (AE)	Number of AE related to embolization	3 months
Serious Adverse Events (SAE)	Number of SAE related to embolization	3 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Guerbet
• Investigators: Principal Investigator: Marc MD Sapoval, PhD, AP-HP, Hôpital Européen Georges Pompidou, Paris

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2021
• Primary Completion (Actual): June 20, 2022
• Study Completion (Actual): September 20, 2022

Study Registration Dates

• First Submitted: January 24, 2021
• First Submitted That Met QC Criteria: January 29, 2021
• First Posted (Actual): February 1, 2021

Study Record Updates

• Last Update Posted (Actual): August 3, 2023
• Last Update Submitted That Met QC Criteria: August 2, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: embolization; musculoskeletal disorders; Lipiodol
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Antineoplastic Agents; Ethiodized Oil
• Other Study ID Numbers: APHP190891; 2020-002206-10 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data (IPD) that underlie results in publication could be shared. IPD detailed in the protocol of a planned metaanalysis could be shared.
• IPD Sharing Time Frame: 2 years after the last publication

IPD Sharing Access Criteria

Data sharing must be accepted by the sponsor and the PI based on a scientific project and scientific involvement of the PI team. Collaboration will be fostered.

Data sharing must respect the agreements made with funders.

Teams wishing obtain IPD must meet the sponsor and IP team to present scientific (and commercial) purpose, IPD needed, format of data transmission, and timeframe. Technical feasibility and financial support will be discussed before mandatory contractual agreement.

Processing of shared data must comply with European General Data Protection Regulation (GDPR).

Teams wishing obtain IPD must meet the sponsor and IP team to present scientific (and commercial) purpose, IPD needed, format of data transmission, and timeframe. Technical feasibility and financial support will be discussed before mandatory contracting

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No