Study design
The BioInsight study (ClinicalTrials.gov identifier: NCT02756338) was a multi-center, prospective, unblinded, post-market single-arm study. The study was approved by the institutional review board at each participating site (Western IRB, The University of Kansas Medical Center Human Research Protection Program IRB, and East Carolina University and Medical Center IRB). The study was conducted in accordance with U.S. Federal regulations and local legal and regulatory requirements. Potential patients were identified by the physician investigators from their general patient population at the approved study site. Patients indicated for continuous arrhythmia monitoring with an ICM who were willing to undergo the insertion procedure in an office setting were invited to participate and written informed consent was obtained prior to study procedures. Patients with a compromised immune system or at high risk of developing infection, as identified by the study physician, infection within the last 30 days, or international normalized ratio (INR) greater than 3.5 (assessed within 7 days of insertion for all patients on warfarin) were excluded. Patients were considered fully enrolled once an in-office insertion with a BioMonitor 2 at an approved study site was attempted by a study investigator beginning with the application of local anesthesia. For this study, office setting was defined as a designated area wherein the patient can lay flat and excluded operating rooms, cardiac catheterization laboratories, and electrophysiology laboratories. All devices were donated by the sponsor as reimbursement for office-based insertion was not common at the time of this study.
Fully enrolled patients were required to complete in-clinic visits at approved study sites for a wound check visit at 7 days after the procedure and a follow-up visit at 90 days post-insertion. Measured device data, including R-wave amplitude and noise burden (percentage of time non-physiologic events were sensed by device per day), were collected via remote daily monitoring and from device interrogation at required clinic visits. Information on adverse events, insertion procedure characteristics, and resource utilization was reported by participating study sites. Patients with an unsuccessful or aborted insertion procedure were planned to be followed for 30 days post-insertion to capture any complications related to the insertion procedure and then exited from the study.
Physicians completed at least two procedures in their standard setting prior to study participation. Insertion techniques were based on physician preference and supplies were obtained at the discretion of the study site. Required resources and supply utilization surveys were collected from all investigative sites.
It was anticipated that at least 75 individual patients would be enrolled, undergo a single in-office insertion attempt at a clinic visit that occurred within 30 days of written informed consent, and then be followed through 90 days post-insertion. Due to the descriptive nature of the study, sample size calculations were not performed using power calculations as no hypothesis test was conducted. Instead, the sample size was determined by the proportion of expected adverse events requiring invasive intervention in combination with an exact binomial one-sided upper 95% confidence interval. The primary objective of the study was to characterize all insertion procedure-related complications requiring invasive intervention to resolve. Potential adverse events were identified through a literature search and pre-defined within the protocol. Insertion procedure-related complications included but were not limited to non-healing device pocket, infection with device pocket identified as primary source, and excessive bleeding. Device-related complications included device migration, skin erosion at site of device, and device protrusion. Infections with a secondary source (i.e., not from the device pocket) were collected and defined as non-procedure, non-device related. An independent Clinical Events Committee consisting of 3 electrophysiologists was responsible for reviewing and adjudicating all reported adverse events.
Secondary objectives included characterization of all insertion procedure-related adverse events (including those not requiring invasive intervention), characterization of the insertion procedure (specifically, insertion success, inserted device orientation, final incision size, and total procedure duration), and characterization of device reported R-wave amplitudes throughout the study duration. Additional data of interest included patient demographics, indication for ICM insertion, prescription of pre- and post-procedure antibiotics, oral anticoagulation usage, overall adverse event rate, and resources used during the insertion procedure.
Statistical analysis
All analysis was intention to treat and included all study participants with a successful insertion and any subject in which the insertion was unsuccessful due to a protocol defined procedure-related adverse event or the insertion procedure was aborted after local anesthesia was applied.
As the study included no pre-defined hypothesis, data analyses were limited to descriptive statistics to present and summarize the data collected in the clinical study. Adverse events were assessed by performing exact, point estimates and one-sided upper 95% confidence intervals. Frequency distributions and cross tabulations are presented for discrete variables. Means, standard deviation, and ranges are presented for continuous variables. SAS version 9.2 (SAS Institute Inc., Cary, NC) was utilized.