Aliskiren Tug-of-War Between Data Monitoring Committee and Regulatory Authorities

A study called ATMOSPHERE (Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure), involved over 7,000 heart failure patients that were assigned to one of three experimental groups.

• Those treated with enalapril, an ACE inhibitor
• Those treated with the renin inhibitor aliskiren
• Those treated with both

After three years and over 7,000 participants, it was found that the group treated with both drugs had a higher risk of low blood pressure symptoms. They also had higher creatinine levels in the blood, suggesting possible kidney stress. Finally, those in the experimental group taking both drugs also had elevated potassium levels.

The New England Journal of Medicine published these results in April. In the same month, an article by the Data Monitoring Committee (DMC) of the study was posted outlining what they felt was inappropriate meddling by regulatory authorities.

The controversy arose because there were two other trials involving aliskiren – ALTITUTE and ASTRONAUT. The ALTITUDE trial prematurely ended because of adverse events associated with patients with diabetes. These concerns prompted the German Federal Institute for Drugs and Medical Devices (BfArM) to investigate. They requested the data collected from the trials; they specifically asked for information about how well diabetic patients tolerated the drug.

Over the next few months and reviews, the DMC continued the ATMOSPHERE study with no revisions. The BfArM could not review the data themselves; so instead, they requested that the DMC review results more often than was mandated. Things came to a head when the Clinical Trial Facilitation Group of the European Union made a decision based on ALTITUDE and ASTRONAUT’s data, but not ATMOSPHERE’s. They asked the sponsor, Novartis, to immediately cease administration of aliskiren to diabetic patients.

The data monitoring committee continues to hold their position that they were carefully monitoring the trial and that it should have been continued due to their close supervision. They state that the trial was safer than ALTITUDE and ASTRONAUT because it had a run-in period, which identified those who reacted adversely to the drug. Those patients were immediately dismissed, and the DMC maintains that this safety precaution validates their decision to continue the study.