The first patient has been enrolled into the phase 4 clinical trial, AUGUSTUS. This two-by-two factorial, randomised controlled trial will evaluate the safety of apixaban (Eliquis, Bristol Myers Squibb and Pfizer) versus warfarin or other vitamin K antagonists (VKA) in patients with nonvalvular atrial fibrillation (NVAF) and a recent acute coronary syndrome or undergoing percutaneous coronary intervention (PCI). In addition, patients will also be randomised to aspirin or placebo.
All patients will receive a P2Y12 inhibitor (such as clopidogrel) in combination with either Eliquis or a VKA. Eliquis is approved to reduce the risk of stroke and systemic embolism in patients with NVAF.
“Limited data are available to inform the use of Eliquis and other oral anticoagulants in NVAF patients who require concomitant dual antiplatelet therapy,” said Renato D Lopes, Duke Clinical Research Institute (DCRI) director of clinical events classification and principle investigator for AUGUSTUS. “With the first patient now enrolled in AUGUSTUS, we will be collecting data that will help inform the safety profile of Eliquis for NVAF patients who have suffered a recent acute coronary syndrome and/or are undergoing PCI.”
“This trial is critical as patients with NVAF frequently have concomitant coronary artery disease, which may result in an acute coronary syndrome event or require PCI that requires antiplatelet therapy.” said John H Alexander, director of cardiovascular research at the DCRI and chair of the AUGUSTUS executive committee.
AUGUSTUS is anticipated to enrol 4,600 eligible patients from 30 countries. The two-by-two factorial design permits for the testing of two hypotheses in the study population. First, it will evaluate whether or not Eliquis is noninferior to a VKA on the combined outcome of major bleeding and clinically relevant non-major bleeding when studied in an open-label manner. Second, in a double-blind manner, it will evaluate whether or not the addition of aspirin to an anticoagulant and P2Y12 inhibitor results in significantly more major and non-major bleeding in the study population.
Secondary objectives include the comparison of Eliquis with VKA (with concomitant P2Y12 therapy) for superiority on major or non-major bleeding; death, stroke, myocardial infarction, stent thrombosis, urgent revascularisation, or re-hospitalisation for any cause; and the comparison of a P2Y12 inhibitor plus aspirin versus a P2Y12 inhibitor alone with either Eliquis or VKA with respect to death, stroke, myocardial infarction, stent thrombosis, or urgent revascularisation and re-hospitalisation for any cause.
The study population will include men and women age 18 and older with NVAF with the planned or existing use of an oral anticoagulant for reducing the risk of thromboembolism. In addition, participants must have had an acute coronary syndrome or PCI with a stent within the prior 14 days, as well as planned use of an approved P2Y12 inhibitor for at least six months.
AUGUSTUS is one of several new clinical trials that will help provide additional information on the safe and appropriate use of Eliquis for certain specific types of patients within currently approved indications.