PALLAS trial
The following information is drawn from a Sanofi Aventis press release.
On July 7th 2011, Sanofi Aventis discontinued the PALLAS Phase IIIb trial in patients with permanent [[Atrial
Fibrillation]] (AF), a population different from the population with non-permanent (paroxysmal) AF for which
Multaq (dronedarone) is currently approved. The decision followed recommendations from the
studys Operations Committee and the Data Monitoring Committee (DMC) which observed a
significant increase in cardiovascular events in the dronedarone arm. The decision to terminate the
study was not related to any hepatic adverse event.
Sanofi has informed regulatory authorities of this decision. The company also has asked all
PALLAS clinical investigators to inform their patients included in the trial to stop taking the study
medication and consult their clinical trial center. This direction applies to the PALLAS study patients
-nly.
The benefit-risk of Multaq remains unchanged in its approved indication in non-permanent AF.
Patients currently taking Multaq should not stop their therapy and should consult their treating
physician should they have any questions.
In the PALLAS population, 70% of the 3,149 patients enrolled had
permanent AF for over 2 years; approximately 70% had NYHA heart failure Class I to III at baseline.
In contrast, in the study supporting the current indication (ATHENA), no patients enrolled had
permanent AF and less than 30% of patients had NYHA heart failure Class I to III. PALLAS
patients were also older than ATHENA patients.
Multaq is currently approved in the EU in adult clinically stable patients with a history of, or current
non-permanent atrial fibrillation (AF) to prevent recurrence of AF or to lower ventricular rate. In the
U.S., Multaq is indicated to reduce the risk of cardiovascular hospitalization in patients with
paroxysmal or persistent atrial fibrillation (AF) or atrial flutter (AFL), with a recent episode of AF/AFL
and associated cardiovascular risk factors (i.e., age >70, hypertension, diabetes, prior
cerebrovascular accident, left atrial diameter 50 mm or left ventricular ejection fraction 
<40%), who are in sinus rhythm or who will be cardioverted.
About PALLAS
PALLAS (Permanent Atrial fibriLLAtion outcome Study using Dronedarone on top of standard
therapy) was a multinational, randomized, double-blind, parallel-group, placebo-controlled,
multicenter Phase IIIb trial comparing the efficacy of dronedarone 400mg twice-daily to placebo in
permanent AF patients. Patients were required to have an age above 65 years with co-morbid
conditions, such as systemic arterial embolism, myocardial infarction, documented coronary artery
disease, prior stroke, symptomatic heart failure, or the combination of age above 75 years,
hypertension and diabetes mellitus. Exclusion criteria included New York Heart Association (NYHA)
Class IV heart failure or unstable NYHA Class III heart failure.
The trial had two composite co-primary endpoints: 1. Major cardiovascular events (stroke, systemic
arterial embolism, myocardial infarction or cardiovascular death). 2. Cardiovascular hospitalization
-r death from any cause.
About Permanent Atrial Fibrillation
According to ACC/AHA/ESC guidelines, permanent AF is the designation given when sinus rhythm
cannot be sustained after cardioversion of AF (medical intervention designed to restore sinus
rhythm) or when the patient and physician have decided to allow AF to continue without further
efforts to restore sinus rhythm. In the Euro Heart Survey one year follow-up, one year mortality in
patients suffering from AF was high and the risk continuously present. Mortality (5.3%) was
comparable with results of previous studies, which is also the case for the observed higher mortality
in permanent AF than in other AF types.