FDA questions safety of Medtronic's ablation system; panel review today
When the FDA’s Circulatory System Device panel meets Oct. 27, panelists will question the safety of Medtronic’s Ablation Frontiers Cardiac Ablation System, and discuss the overall risk/benefit profile of the device. In a previously released report, the FDA noted that the primary efficacy endpoints were met during the trial evaluating the device, but safety endpoints were not, making the agency question the device’s safety. During the meeting, the FDA said it will be seeking comments from committee members on these safety considerations.
Medtronic’s Frontier ablation system is indicated for the treatment of symptomatic, drug refractory, persistent atrial fibrillation (AF) or longstanding AF of up to four years. The system, originally developed by Ablation Frontiers, received CE Mark in December 2006. Medtronic acquired Ablation Frontiers in February 2009.
The ablation system includes:
The clinical trial to study this device was a multicenter, randomized, unblinded trial that randomized patients to receive ablation management of medical therapy. During the trial, 210 patients with symptomatic permanent AF who had failed at least one Class I or III anti-arrhythmic drugs were enrolled.
As far as safety goes, FDA said that the trial was “not powered for the chronic safety endpoint and the pre-specified overall study success rule did not include the chronic safety endpoint.” However, of the 79 patients enrolled in the ablation management arm, 44 achieved chronic effectiveness compared to 14 of the 57 patients randomized to the medical management arm.
The FDA said that it is concerned with the overall rate of serious device- and procedure-related adverse events in patients who underwent one study procedure. Additionally, the agency raised concern with the high rates of peri-procedural stroke found in the trial. Most commonly, rates of peri-procedural stroke reported in catheter AF literature ranges from 0 to 1.7 percent. In comparison, five subjects experienced a stroke within one month of the study procedure, making the peri-procedural stroke rate 2.8 percent, with an upper bound limit of 6.5 percent.
The FDA said that it is also concerned with the length of the follow-up period proposed in the primary endpoint and offered that it may not be sufficient to assess the durability of the ablation treatment. Additionally, the agency said that the premarket study of the device has many limitations and that it was concerned about the definition for treatment success, which was proposed for the post-approval study.
While the trial showed that the ablation system was superior to medical management at six months, 55.8 percent vs. 26.4 percent, the FDA said that it is still concerned with the overall safety profile of the device.
The FDA said it will seek panel input on the overall risk-benefit profile of the device at the committee meeting Oct. 27.
Medtronic’s Frontier ablation system is indicated for the treatment of symptomatic, drug refractory, persistent atrial fibrillation (AF) or longstanding AF of up to four years. The system, originally developed by Ablation Frontiers, received CE Mark in December 2006. Medtronic acquired Ablation Frontiers in February 2009.
The ablation system includes:
- The Multi-Array Ablation Catheter (MAAC), designed to create lesions in the left atrium that target Complex Fractionated Atrial Electrograms (CFAEs).
- The Multi-Array Septal Catheter (MASC), designed to create lesions on the septal wall of the left atrium that target CFAEs.
- The Pulmonary Vein Ablation Catheter (PVAC), designed to create encircling lesions to isolate the pulmonary veins (PVs)
- The GENius Multi-Channel RF Generator, designed to deliver radio frequency (RF) energy in unipolar mode, bipolar mode, or combinations thereof to operator-selected ablation electrodes on any of the three system catheters.
The clinical trial to study this device was a multicenter, randomized, unblinded trial that randomized patients to receive ablation management of medical therapy. During the trial, 210 patients with symptomatic permanent AF who had failed at least one Class I or III anti-arrhythmic drugs were enrolled.
As far as safety goes, FDA said that the trial was “not powered for the chronic safety endpoint and the pre-specified overall study success rule did not include the chronic safety endpoint.” However, of the 79 patients enrolled in the ablation management arm, 44 achieved chronic effectiveness compared to 14 of the 57 patients randomized to the medical management arm.
The FDA said that it is concerned with the overall rate of serious device- and procedure-related adverse events in patients who underwent one study procedure. Additionally, the agency raised concern with the high rates of peri-procedural stroke found in the trial. Most commonly, rates of peri-procedural stroke reported in catheter AF literature ranges from 0 to 1.7 percent. In comparison, five subjects experienced a stroke within one month of the study procedure, making the peri-procedural stroke rate 2.8 percent, with an upper bound limit of 6.5 percent.
The FDA said that it is also concerned with the length of the follow-up period proposed in the primary endpoint and offered that it may not be sufficient to assess the durability of the ablation treatment. Additionally, the agency said that the premarket study of the device has many limitations and that it was concerned about the definition for treatment success, which was proposed for the post-approval study.
While the trial showed that the ablation system was superior to medical management at six months, 55.8 percent vs. 26.4 percent, the FDA said that it is still concerned with the overall safety profile of the device.
The FDA said it will seek panel input on the overall risk-benefit profile of the device at the committee meeting Oct. 27.