Work Package 1: Primary Care Clinical Trial (RAPIDA).
The ‘RAPIDA’ trial (RAPid test for Investigating complaints possibly due to Acute Coronary Syndrome (ACS)), is a study based at the universities of Maastricht, Netherlands and Leuven, Belgium. The objective was to investigate the use of an H-FABP test in combination with standard GP diagnostic procedures, anticipating a reduction in the 7% of ACS cases that are missed in error and reducing the referrals to cardiology for whom ACS is subsequently eliminated as a diagnosis. With 303 patients had been included data collection ended in December 2016. The data recommends a review of the diagnostic threshold for heart attacks to be reduced to include Unstable Angina in the positive range. The Model Analysis of Economic Costs identified that the cost of false referral in the Netherlands was €162MM on an annual basis. Providing 29% of unnecessary admissions are prevented, the use of H-FABP in a GP setting is cost neutral and missed diagnoses reduced. These data were published in the peer reviewed journal Primary Health Care Research & Development in December 2017.
Work Package 2: TSB Emergency Medicine Trial (RapidEx)
The RapidEx (Rapid Exclusion of ACS) trial has the objective to assess whether a novel point of care device for heart-type fatty acid binding protein (H-FABP) can be used to accurately rule out Acute Myocardial Infarction (AMI, or heart attack) when used alongside other clinical information as part of the Manchester Acute Coronary Syndromes (MACS) decision rule within 3 hours of arrival in an Emergency Department (ED). First data were available in May 2016, when the interoperator variability study was published in the peer review journal Clinical Biochemistry (Al Mashali et al, Clinical Biochemistry 49 (2016) 1199–1201), with a Cohen’s kappa coefficient of .81, “Near Perfect Agreement”. Principal Investigator Professor Rick Body of Manchester University Hospitals NHS Foundation Trust engaged a further 14 Emergency Departments across NHS England to boost the speed of the trial and to provide evidence reliability of the Clinical Decision Rule. In July 2017, a total of 1600 patients had been included. A short paper on the trial was presented by Professor Body at the Royal College of Emergency Medicine Annual Scientific Conference, Liverpool, UK in October 2017. In summary the MACS protocol using H-FABP True Rapid Test at presentation gave a Negative Predictive Value of 99.3% (95%CI 98.0 – 99.8%), matching an innovative exclusion protocol (T-MACS) using high sensitivity cardiac troponin. The Health Economic Study Report (Thompson & Davison, Manchester University) concludes the modified MACS protocol using H-FABP True Rapid Test is economically advantageous.
Whilst the technology worked as expected, the study recommends review of the diagnostic threshold to be effective for exclusion of ACS in early onset of chest pain, this research has already started and should be results in a revised CE marked test during 2018. Additionally it is found that a positive H-FABP result using the point of care assay manufactured by FABPulous BV increases the probability of ACS, regardless of a patient’s baseline ECG and hs-cTn concentrations, this might facilitate early specialist care for high risk patients, which could potentially lead to improved patient outcomes. Finally, the study derived a new protocol using H-FABP True Rapid Test provides a unique opportunity to improve patient risk stratification in pre-hospital settings with a 5-minute, equipment-free solution. The proposed FABPuMACS clinical decision rule will be investigated further.
Work Package 3: Transfer of manufacturing from North America to Helvoet, Netherlands
The prototype CE-marked H-FABP True Rapid Test was hand-manufactured through the activities of 4 companies in 4 sites across the USA and Canada. To improve the manufacturing process, shortening the management channels, increasing capacity and reducing cost of goods, Helvoet BV (Tilburg, Netherlands) was chosen on best value, proximity, proven record and quality assurance. Using Reverse Engineering, the precision and reliability of the Sample Preparation Device was improved, new production moulds, materials and assembly processes have now been established at the one site within the EU. The Design Manufacturing File is completed for the basic product. Both Helvoet and FABPulous have received ISO 13485:2016 certification for manufacturing of medical devices. Packaging, labelling (including UDI) and instructions for use have been revised fulfils the latest regulatory requirements. Cost of goods has been reduced by 63% compared with the pre-transfer costs and capacity has increased to meet short- to medium-term demand.
