just listened to the full CC, here's my take on PROACTION:
STUDY DESIGN: -give patients coming to the ER with CHF natrecor, dobutamine or milrinoe. -assess endpoints including length of stay in the hospital, readmission, and cost.
RESULTS: about 250 patients enrolled only 55% admitted to the hospital only 4 patients admitted to ICU
the INITIAL GOALS of the study were to show that natrecor is cost-effective for in-hospital use; however because they gave natrecor in the ED, only 4 patients made it to the ICU, so there are not enough patients to show benefit in the use in the ICU.
Dr. Horton is now saying that PROACTION's goal is to show that natrecor is SAFE to use in the ER and she is downplaying any expectations that PROACTION will show "definitive pharmacoeconomic benefits". she guided expectations even lower when she said that this is "really only a pilot study."
the main flaw in PROACTION is that natrecor should have been compared with NTG not dobutamine or milirone -- in addition, Dr. Horton said that most of the patients got treated with natrecor anyways, because milirone and dobutamine are not first-line agents for treatment of CHF.
secondly, patients should have been treated with natrecor vs. NTG AFTER admission to the ICU not in the ED setting. due to exorbitant costs, natrecor can show the most benefit in the ICU setting.
thirdly, there are many causes for heart failure in patients who come through the ER. while some of these patients have only heart failure, some of these patients have heart failure that is triggered by other reasons, namely, myocardial infarction and infection. these latter patients will be admitted regardless of whether or not their "heart failure" is corrected in the ER because they need to get worked up for a heart attack or treated for their pneumonias. unless, PROACTION and future SCIOS trials leave out this group of patients, any cost-savings of natrecor will be underestimated. because of cost issues, this is probably why natrecor is still only indicated for patients with the most severe CHF in the ICU, not just any old patient with mild CHF coming into the ER.
fourth, they had major enrollment issues -- they only got 250 patients enrolled. with such few patients there is less chance to show statistically significant results. Dr. Horton admits to making several assumptions for PROACTION, which probably led to such a low enrollment.
finally, while "only 55%" of natrecor patients were ultimately admitted to the hospital, they really have no controls to compare. in order to understand if 55% admission rate is significantly lower, we need to compare the patients who got natrecor vs. the patients who didn't. in other words, what percent of the patients who DID NOT recieve natrecor got admitted? it sounds like we do not know, because most of the patients in the trial got natrecor anyways. this explains why Dr. Horton is now calling this a "SAFETY" trial for use in the ER.
at the end, Dr. Horton, hesitates before answering "yes" to the question: "Does natrecor lower admission rates to the hospital?" But I'm not sure what she is comparing the 55% admission rate with. She states that she is assuming an average of 80-90% admission rate for patients without natrecor treatment in the ER. However, like I said earlier, they need to show this in one large clinical trial -- giving about everyone in the PROACTION trial natrecor isn't gonna help.
throughout the CC Dr. Horton says: PROACTION is "not a definitive study for pharmacoeconomic effects in the hospital".
I believe you are wrong when you say that most of the patients in the study got Natrecor. I have asked Scios to give me the actual number and I expect that Wendy will do so. This study compared Natrecor plus standard treatment to Placebo plus standard treatment. I find nothing in Dr. Horton's statement that is inconsistent with the purpose as stated in the original press release. It was called a pilot study from the beginning. The design was not to give Natrecor, dobutamine or milrinone as you stated. In fact, Dr. Horton said that inotropes are rarely used in the ER. Also your apparent belief that Natrecor is only used as a replacement for NTG is incorrect. The only reason that Natrecor was compared to NTG in VMAC was because FDA wanted the comparison to assess the relative safety of the two drugs. Some of the other benefits of Natrecor besides vasodilation are increased elimination of fluids and salt and increased cardiac output.
2. PROACTION is looking at the wrong group of patients.
3. PROACTION will not be able to show the following endpoints: economic benefits of natrecor and reduced length of hospital stay.
4. PROACTION might be able to show decrease admission rates with natrecor use, but they'll have to find a study performed somewhere else in the past showing the admission rate of patients with CHF when given NTG in the ER. This is a bit convoluted.
5. They should be able to show that PROACTION is safe to use in the ER setting.
I'm disappointed by the PROACTION study design and I'll be interested in what they say in the July CC, but i'm not holding my breath. It looks like PROACTION will not make natrecor "standard of care" and thus will not be the catalyst we need to move this sloth stock up.
To get to "standard of care" we need either: (1) definitive pharmacoeconomic benefits of natrecor or (2) morbidity & mortality benefits. They might be able to show the latter with the ADHERE study, but this won't be done for at least 2-3 years.
If anyone's got the actual enrollment guidelines for PROACTION, post it -- it might help clear some issues up.
PROACTION (Prospective Randomized Outcomes Study of Acutely Decompensated Congestive Heart Failure Treated Initially in Outpatients with Natrecor) is a pilot study designed to compare the clinical effects, safety profile and economic impact of standard therapy plus Natrecor to standard therapy plus placebo in 250 acute CHF patients treated in the Emergency Department (ED)/Observation Unit (OU). The majority of the one million hospitalizations each year for this indication begin in either the ED or the OU. Standard therapy will consist of any treatments physicians would typically use for these patients. Scios expects to complete this study in the third quarter of 2001.
�This study is designed to look at numerous measures that factor in the overall cost of hospitalization for patients with acute CHF,� said Charles L. Emerman, M.D., Chairman, Department of Emergency Medicine, The Cleveland Clinic Foundation and MetroHealth Medical Center. �We will examine admission to the hospital following evaluation and treatment in the ED/OU, and other pharmacoeconomic measures. We believe Natrecor�s fixed-dose administration compared to the titration schedule and safety profile of existing therapies may result in a lower overall cost of care for patients hospitalized with acute CHF.�