Like the presentation says,little or no competition.None of the big boys seem to want to try anymore.IMO Big partnerships are in the waiting.I think CTSO really could be the SOC for a very long time.
Thanks for bringing this article to our attention- and to Andy for posting the entire publication. I e-mailed the author, Crystal Phend, a copy of the recent conference call transcript and slide show presentation. The IL-6 reduction in the case study Dr. Chan shared was astonishing over the first four day period. I'll let you know if she responds-
Statins Flop in Sepsis and COPD
Published: May 18, 2014
By Crystal Phend, Senior Staff Writer, MedPage Today
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco
SAN DIEGO -- Statins don't prevent chronic obstructive pulmonary disease exacerbations or improve outcomes in sepsis-related respiratory failure, a series of trials showed.
For patients with acute respiratory distress syndrome (ARDS) from sepsis in the ICU, rosuvastatin (Crestor) didn't cut 60-day in-hospital mortality compared with placebo (28.5% versus 24.9%, P=0.21) or boost ventilator-free days (mean 15.1 in both groups, P=0.96).
Putting patients on the lipid-lowering drug actually contributed to hepatic and renal failure, Jonathon D. Truwit, MD, of the Medical College of Wisconsin in Milwaukee, and colleagues found in the ARDS Clinical Trials Network study.
In the STATCOPE trial, simvastatin (Zocor) didn't prevent COPD exacerbations compared with placebo (1.36 versus 1.39 mean per person-year, P=0.54) or delay them (median 223 versus 231 days to first exacerbation, P=0.34), Gerard Criner, MD, of Temple University in Philadelphia, reported at the meeting.
Both National Heart, Lung, and Blood Institute-sponsored trials were reported at a late-breaking clinical trials session here at the American Thoracic Society meeting and released simultaneously online in the New England Journal of Medicine.
A Worthwhile Strike-Out?
Despite striking out, the trials weren't a waste of public funds, Jeffrey M. Drazen, MD, editor-in-chief of that journal, and Annetine C. Gelijns, PhD, of Mount Sinai School of Medicine in New York City, argued in an accompanying editorial.
"In both diseases, our therapeutic armamentarium is meager, the public health need is great, and the intervention was reasonable and had face validity," they wrote.
There was a solid rationale for both that the pleomorphic anti-inflammatory effects of statins would pay off in the conditions for which inflammation is thought to drive disease pathobiology, the editorial noted.
A third randomized trial presented at the meeting -- RODEO -- confirmed reduced systemic inflammation with short-term treatment with rosuvastatin in stable COPD patients without known cardiovascular disease.
But again it showed no benefit for pulmonary function, Anke Neukamm, MD, of Akershus University Hospital in Oslo, Norway, and colleagues found.
In the 99-patient trial, 10 mg rosuvastatin daily for 12 weeks reduced high-sensitivity C-reactive protein and cut the rise in interleukin-6 as markers of inflammation compared with placebo (P=0.017 and P=0.028, respectively).
But lung function as measured by forced expiratory volume in 1 second (FEV1) and the ratio of FEV1 to forced vital capacity showed no difference between groups (P=0.462 and P=0.292).
Observational studies had suggested better outcomes in patients on statins in both COPD and sepsis.
Despite the negative results in the randomized trials, "they had to be done," Drazen and Gelijns wrote. "It would have been a big mistake to accept the findings without a test."
This kind of "discovery-in-practice" route to clinical trials is likely to be increasingly seen as electronic health records are exploited for big data, they noted.
Statins for ARDS in Sepsis
The ARDS trial was stopped for futility after 745 of the planned 1,000 patients had been enrolled at 44 participating hospitals.
Participants were randomized to a 40-mg loading dose of either rosuvastatin or placebo within 48 hours of onset of ARDS and then daily maintenance dosing at 20 mg, or 10 mg for those with elevated serum creatinine levels not on renal-replacement therapy.
Treatment continued for up to 28 days but was stopped early in case of ICU discharge, hospital discharge, or death.
Secondary outcomes of mean tidal volume, positive end-expiratory pressure, fluid balance, oxygenation index, plateau pressure, static compliance of the respiratory system, minute ventilation, arterial partial pressure of carbon dioxide, and arterial pH all showed no difference between treatment groups.
Nor were there differences in the primary endpoint of mortality before hospital discharge home or until study day 60 if the patient was still in a health care facility for the subgroup of patients in shock at baseline (36% on statin versus 32% on placebo, P=0.39), or in those who used a statin before their critical illness (31% versus 20%, P=0.14).
While rosuvastatin wasn't associated with higher incidence of serum creatine kinase levels over 10 times the upper limit of normal, it did result in fewer days free of renal failure to day 14 (10.1 versus 11.0, P=0.01) and fewer days free of hepatic failure to day 14 (10.8 versus 11.8, P=0.003).
"These differences in organ-failure-free days were small, and their significance may be spurious owing to the number of secondary end points analyzed," Truwit's group cautioned. "However, we cannot rule out a detrimental effect of rosuvastatin."
The study used a moderate statin dose selected for its potentially fewer drug interactions. But it didn't achieve the expected plasma levels of the drug, which could have accounted for the lack of efficacy, they suggested.
Given the signs of potential toxicity, though, higher doses might not have been appropriate, they argued.
Atorvastatin (Lipitor) and simvastatin didn't reduce mortality either in a meta-analysis of five smaller randomized, controlled trials with a total of 650 sepsis patients.
"These results, coupled with those of smaller randomized trials of other statins, do not provide support for initiating or continuing statin therapy for the treatment of sepsis-associated ARDS," Truwit's group concluded.
Perhaps the observational findings of benefit had been due to confounding from better access to health care and thus earlier initiation of antibiotics in patients who come in on statins, or statins have preventive effects when taken long-term before infection that couldn't be replicated short-term after infection, they suggested.
Statins for COPD
Preventive use of simvastatin for COPD also didn't pan out in STATCOPE (Prospective Randomized Placebo-Controlled Trial of Simvastatin in the Prevention of COPD Exacerbations), according to Criner and colleagues.
The trial was halted early for futility after enrolling 878 patients with moderate to severe COPD, a smoking history of 10 or more pack-years, on supplemental oxygen or treatment with glucocorticoids or antibiotics, or an emergency department visit or hospitalization for COPD within the prior year.
Randomization to simvastatin at a daily dose of 40 mg didn't impact the primary endpoint of annual exacerbation rates in any patient subgroup.
Nor did the drug improve lung function as assessed spirometrically, or general or respiratory-specific quality of life.
Deaths and other serious adverse events came out similar between groups too.
The study excluded patients with diabetes or cardiovascular disease and those who were taking statins or who should have been based on national guidelines.
That may have explained the difference between the trial results and those of previous positive studies, Criner's group suggested.
"The underuse of statins in persons with cardiac risk factors who have been included in retrospective studies may account in part for the differences between our findings and those previously reported," they wrote.
They called their findings conclusive, while acknowledging it wasn't clear whether the results would generalize to less severe COPD.
Another limitation was that the trial didn't use a marker of systemic inflammation, like serum C-reactive protein (CRP) to screen for enrollment, which "may have limited our ability to detect an effect of simvastatin in reducing the rate of exacerbations," they noted.
STATCOPE was funded by the National Heart, Lung, and Blood Institute (NHLBI) and the Canadian Institutes of Health Research.
Truwit's trial was funded by the NHLBI and the Investigator-Sponsored Study Program of AstraZeneca.
Criner disclosed relationships with the NHLBI, GlaxoSmithKline, Boehringer Ingelheim, Pneumrx, Aeris, Pulmonx, Respimat, MedImmune, AstraZeneca, Ikaria, Holaria, Celerion, Almirall, and CSA Medical.
Drazen disclosed relationships with the New England Journal of Medicine.
Gelijns disclosed relationships with MERS, a private start-up company with a medical event reporting system.
Truwit disclosed relationships with the NHLBI ARDSNet.