Following a positive interim analysis showing that fractional flow-reserve-guided PCI was superior to optimal medical treatment, an independent Data and Safety Monitoring Board (DSMB) has recommended that patient enrollment in the ongoing FAME II trial be stopped. The news was announced by the trial sponsor, St. Jude Medical.
FAME II (Fractional Flow Reserve-Guided Percutaneous Coronary Intervention Plus Optimal Medical Treatment Versus Optimal Medical Treatment Alone in Patients With Stable Coronary Artery Disease) investigators had planned to randomize 1,832 patients with stable coronary artery disease to either PCI guided by FFR plus optimal medical treatment (OMT) or OMT alone. At the time of the announcement 1,219 patients had been randomized.
According to the company, the DSMB recommendation was based on an increase in the risk of major adverse cardiac events (MACE) in patients randomized to OMT alone. “In particular, patients receiving OMT alone experienced a highly statistically significant increased risk of hospital readmission and urgent revascularization, and the DSMB determined that this difference was highly unlikely to change with inclusion of more patients,” the company stated. There were no significant differences in the rates of death or MI.
It should be noted that all patients in FAME II underwent FFR prior to randomization, according to the original announcement of the trial. Patients who had hemodynamically significant lesions as assessed by FFR were then randomized to PCI or OMT. The trial was designed to address the limitations of COURAGE, in which CAD patients as documented by angiography were randomized to PCI or OMT. However, the followup to COURAGE, the ISCHEMIA trial, will randomize ischemic patients to PCI or OMT without prior angiography. FAME II does not appear to address the question of which patients should undergo angiography in the first place.
Here is the press release from St. Jude:
Independent Data Safety Monitoring Board Recommends St. Jude Medical’s FAME II Clinical Trial Stop Enrollment Following Positive Interim Analysis
Follow-up trial to landmark FAME trial examines benefits of using FFR-guided assessment for stent procedures with optimal medical treatment compared to optimal medical treatment alone
ST. PAUL, Minn., Jan 18, 2012 (BUSINESS WIRE) –St. Jude Medical, Inc. (NYSE:STJ), a global medical device company, announced today that an interim analysis of the FAME II trial has found a highly statistically significant reduction in the need for hospital readmission and urgent revascularization when Fractional Flow Reserve (FFR)-guided assessment was used to direct treatment in patients with coronary artery disease. As a result of the positive interim analysis, the FAME II independent Data Safety Monitoring Board (DSMB) has recommended investigators stop patient enrollment in this trial as the DSMB considers it unethical to continue to randomize patients to optimal medical therapy (OMT) alone.
FFR is a physiological index used to determine the hemodynamic severity of narrowings in the coronary arteries, and is measured using St. Jude Medical’s PressureWire(TM) Aeris and PressureWire(TM) Certus. FFR specifically identifies which coronary narrowings are responsible for obstructing the flow of blood to a patient’s heart muscle (called ischemia), and guides the interventional cardiologist in determining which lesions warrant stenting, resulting in improved patient outcomes and reduced healthcare costs.
The goal of the St. Jude Medical sponsored FAME II (Fractional Flow Reserve (FFR)-Guided Percutaneous Coronary Intervention Plus Optimal Medical Treatment vs. Optimal Medical Treatment Alone in Patients with Stable Coronary Artery Disease) trial is to further study the role of FFR in the treatment of stable coronary artery disease by comparing percutaneous coronary intervention (PCI) guided by FFR plus OMT to OMT alone.
The DSMB recommended that St. Jude Medical stop patient enrollment in its FAME II trial due to increased patient risk of major adverse cardiac events (MACE) among patients randomized to OMT alone compared to patients randomized to OMT plus FFR-guided PCI. In particular, patients receiving OMT alone experienced a highly statistically significant increased risk of hospital readmission and urgent revascularization, and the DSMB determined that this difference was highly unlikely to change with inclusion of more patients. The data currently reflect no observed difference in the rates of death or heart attack.
The FAME II trial may provide new insights about the benefits of coronary intervention and answer questions raised by the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial, which demonstrated no difference in the outcomes between PCI plus OMT compared to OMT alone. However, the COURAGE study did not require use of PressureWire(TM) FFR measurement technology.
“The FAME II trial is unprecedented in its ability to provide further answers and evidence regarding the optimal way to treat patients with coronary artery disease and myocardial ischemia,” said Bernard De Bruyne, M.D., Ph.D., of the OLV Clinic in Aalst, Belgium, and coordinating clinical investigator of the FAME II trial. “What we observed to date regarding urgent revascularizations validates the profound role that FFR-guided therapy has in improving patient outcomes. This is further evidence that FFR should be considered the standard of care for patients with coronary artery disease.”
The FAME II trial will continue following patients currently enrolled according to the trial protocol and will not enroll any new patients. The trial randomized 1,219 patients with stable coronary artery disease in 28 centers in Europe, the U.S. and Canada.
“The original FAME trial demonstrated that FFR guidance improves outcomes in patients with stable coronary artery disease and two or three vessel disease. Today, FAME II confirms that PCI is beneficial for patients with one, two and three vessel disease whose ischemia has been documented by FFR,” said Frank Callaghan, president of the St. Jude Medical Cardiovascular Division. “Due to the statistically and clinically compelling differences in the number of patients returning to the hospital for an urgent revascularization procedure – which can be considered a surrogate for a repeat heart attack or death – we support the recommendation of the DSMB and the trial’s Steering Committee. We expect the data will continue to reveal the important role that FFR plays in developing an optimal treatment strategy.”
Data will be published as information is analyzed, with initial results expected to be presented in 2012.
About the Original FAME Trial
The original FAME (Fractional Flow Reserve (FFR) vs. Angiography in Multivessel Evaluation) trial was a randomized, prospective, multi-center trial which enrolled 1,005 patients with multivessel coronary artery disease. The FAME study compared outcomes for patients whose treatment was guided by FFR to those whose treatment was guided only by angiography using St. Jude Medical’s PressureWire Certus technology. The 12-month results, published in the Jan. 15, 2009 issue of the New England Journal of Medicine, demonstrated that instances MACE were reduced by 28 percent for patients whose treatment was guided by FFR rather than by standard angiography alone. Two-year results demonstrated that patients who received FFR-guided treatment continued to experience improved outcomes over time, including a 34 percent reduction in risk of death or heart attack.
About St. Jude Medical
St. Jude Medical develops medical technology and services that focus on putting more control into the hands of those who treat cardiac, neurological and chronic pain patients worldwide. The company is dedicated to advancing the practice of medicine by reducing risk wherever possible and contributing to successful outcomes for every patient. St. Jude Medical is headquartered in St. Paul, Minn. and has four major focus areas that include: cardiac rhythm management, atrial fibrillation, cardiovascular and neuromodulation. For more information, please visit sjm.com.
This news release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that involve risks and uncertainties. Such forward-looking statements include the expectations, plans and prospects for the Company, including potential clinical successes, anticipated regulatory approvals and future product launches, and projected revenues, margins, earnings and market shares. The statements made by the Company are based upon management’s current expectations and are subject to certain risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. These risks and uncertainties include market conditions and other factors beyond the Company’s control and the risk factors and other cautionary statements described in the Company’s filings with the SEC, including those described in the Risk Factors and Cautionary Statements sections of the Company’s Annual Report on Form 10-K for the fiscal year ended January 1, 2011 and Quarterly Report on Form 10-Q for the fiscal quarter ended October 1, 2011. The Company does not intend to update these statements and undertakes no duty to any person to provide any such update under any circumstance.
SOURCE: St. Jude Medical, Inc