Biolimus A9™ (BA9™) Drug Coated Balloon (DCB) Study (REFORM)

A Prospective, Randomized, Non-Inferiority Trial to Determine the Safety and Efficacy of the BA9TM Drug Coated Balloon for the Treatment of In-Stent Restenosis: First-in-Man Trial (REFORM)

The study is a Prospective, Randomized, Non-Inferiority Trial to Determine the Safety and Efficacy of the BA9™ Drug Coated Balloon for the Treatment of In-Stent Restenosis. It is a First-in-Man Trial.

Study Overview

• Status: Active, not recruiting
• Conditions: Coronary Artery Disease; In-Stent Restenosis
• Intervention / Treatment: Device: Biolimus A9 Drug Coated Balloon; Device: SeQuent Please Paclitaxel Drug Coated Balloon

Detailed Description

This clinical trial will serve as a first-in-human (FIH) experience for the BA9™ DCB in a population of patients with coronary artery disease who have an indication for interventional treatment of in-stent restenosis (ISR) in a bare-metal stent (BMS) or drug-eluting stent (DES).

The study uses a prospective, multi-center, single blind, randomized controlled trial design to enroll 195 patients. The study will seek to prove that the BA9-DCB is non-inferior to the approved CE marked Sequent Please® Paclitaxel Coated Balloon with respect to % Diameter Stenosis and has similar safety characteristics.

• Study Type: Interventional
• Enrollment (Actual): 201
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Bad Segeberg, Germany
    • Heart Center, Segeberger Kliniken
  • Leipzig, Germany
    • Heart Center Leipzig - University of Leipzig
  • Wittenberg, Germany
    • Evangelisches Krankenhaus Paul Gerhardt Stift
• Ireland
  • Dublin, Ireland
    • Mater Private Hospital
  • Galway, Ireland
    • University Hospital Galway
• Italy
  • Milano, Italy
    • Centro Cardiologico Monzino
• Spain
  • Barcelona, Spain
    • Hospital Clinic de Barcelona
  • Madrid, Spain
    • Hospital Clinico San Carlos
  • Madrid, Spain
    • Hospital Universitario de La Princesa
• United Kingdom
  • Bournemouth, United Kingdom
    • Royal Bournemouth Hospital
  • Cardiff, United Kingdom
    • University Hospital of Wales
  • Craigavon, United Kingdom
    • Craigavon Cardiac Centre
  • Dorchester, United Kingdom
    • Dorset County Hospital
  • Londonderry, United Kingdom
    • Altnagelvin Area Hospital
  • Worcester, United Kingdom
    • Worcestershire Royal Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 86 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients presenting with in-stent restenosis (ISR) and clinical symptoms of ischemia and/or (i) evidence of ischemia on non-invasive testing or (ii) hemodynamically relevant lesion defined by FFR ≤ 0.80 or iFR ≤ 0.89 or > 90% stenosis.
• Patient presenting with a lesion that can be fully covered with one DCB length. - Patients can have up to two index lesions with ISR, which can both be treated and evaluated.
• Patient has provided written informed consent
• Age ≥ 18 years.
• Patient is willing and able to comply with the study procedures and follow-up.

Exclusion Criteria:

• Patient presents with a ST-elevation myocardial infarction (STEMI) or had an acute MI within 48 hours prior to presentation (according to the universal definition of myocardial infarction).
• Patient with acute cardiac decompensation or acute cardiogenic shock
• Documented left ventricular ejection fraction (LVEF) ≤ 30%
• Patient with impaired renal function (glomerular filtration rate < 80 mL/min/1.73 m2).
• More than 2 epicardial vessels requiring revascularization
• Significant left main stenosis (by visual estimation) or an ISR located in the left main (LM).
• Patient has an ISR lesion that cannot be covered with one DCB length.
• Patient has an ISR in the target segment in a stent of a smaller diameter than 2.5mm.
• Severe calcification that might prevent a sufficient expansion of the DCB, if not pre-treated with rotablation or a shockwave application device.
• Known hypersensitivity or contraindication to biolimus, paclitaxcel, aspirin, thienopyridines, or iodinated contrast that cannot be pre-treated.
• Pregnant and/or breast-feeding females or females who intend to become pregnant during the time of the study.
• Subject currently enrolled in other investigational device or drug trial in which the primary endpoint has not yet been reached.
• Anticipated difficulties to complete the angiographic follow-up study.
• Patient with a life expectancy of less than 12 months.
• Patients lacking mental capacity (i.e. patients suffering from dementia and others) to provide informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Biolimus A9™ Drug Coated Balloon; Patients who meet the eligibility criteria and who are randomised to this arm, will receive treatment with the Biolimus A9™ Drug Coated Balloon	Device: Biolimus A9 Drug Coated Balloon; A non-surgical procedure that uses a catheter to place a semi-compliant angioplasty drug coated balloon to open up coronary arteries that have been narrowed by atherosclerosis. The balloon is inflated to treat the stenosis and transfer the drug to arterial wall, and then is deflated and withdrawn.
Active Comparator: Sequent ® Please Paclitaxel coated balloon; Patients who meet the eligibility criteria and who are randomised to this arm, will receive treatment with the Sequent ® Please Paclitaxel coated balloon	Device: SeQuent Please Paclitaxel Drug Coated Balloon; A non-surgical procedure that uses a catheter to place a semi-compliant angioplasty drug coated balloon to open up coronary arteries that have been narrowed by atherosclerosis. The balloon is inflated to treat the stenosis and transfer the drug to arterial wall, and then is deflated and withdrawn.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Diameter Stenosis (DS)	Percent DS of the target segment assessed by quantitative coronary angiography (QCA)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Target lesion failure	Taget lesion failure defined as a composite of cardiovascular death, any target vessel myocardial infarction, coronary artery bypass graft and clinically driven target lesion revascularization	1 month, 6 months, 1 year and 2 years
Target vessel failure	Target vessel failure defined as a composite of cardiovascular death, any target vessel myocardial infarction, and clinically driven target vessel revascularization	1 month, 6 months, 1 year and 2 years

Collaborators and Investigators

• Sponsor: Biosensors Europe SA
• Investigators: Principal Investigator: Robert A Byrne, MD, PhD, Mater Private Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2020
• Primary Completion (Anticipated): April 1, 2023
• Study Completion (Anticipated): April 1, 2024

Study Registration Dates

• First Submitted: August 27, 2019
• First Submitted That Met QC Criteria: September 4, 2019
• First Posted (Actual): September 6, 2019

Study Record Updates

• Last Update Posted (Actual): August 10, 2022
• Last Update Submitted That Met QC Criteria: August 9, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Drug-Coated Balloon
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Umirolimus
• Other Study ID Numbers: 19-EU-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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