Patients with chronic heart failure who agree to take part in clinical trials have a better prognosis than those who do not, according to a study reported in the November European Journal of Heart Failure.(1) The finding, say the authors, may even call into question the commonplace ethical requirement of most clinical trials that by choosing not to take part in the study a patient will not be disadvantaged.

The study was a follow-up of 2332 consecutive patients diagnosed with chronic heart failure at Castle Hill Hospital, Hull, UK. At their initial visit to the clinic all were asked if they would be willing to take part in clinical research projects. After a median follow-up of 55.7 months, analysis of the full cohort showed that 792 (34%) had died. However, survival was significantly associated with a willingness to take part in clinical trials, which more than halved the risk of death (hazard ratio 0.33).

The authors note that outcomes for patients with chronic heart failure are generally very poor; epidemiological studies show that around 40% of patients diagnosed with chronic heart failure die within a year of diagnosis.(2) “However,” says investigator Dr Andrew Clark from Castle Hill Hospital, “two-year mortality rate in recent trials of chronic heart failure trials has been in the order of 20%. And even in studies of very sick patients, mortality has only been 30%. So we wanted to see if taking part in a clinical trial was associated with a beneficial outcome.”

Additionally, to explore the effect on survival of actually entering a clinical trial (rather than simply indicating a willingness to take part) survival after the first year was compared between “willing” patients who were recruited to a trial and willing patients who were not.

The single most powerful predictor of all-cause mortality in the whole cohort (p<0.0001) - from a multivariate model of 19 clinical and social variables - was willingness to take part in a trial, with a "protective" hazard ratio of 0.33 (95% CI, 0.26-0.40). This was a predictor of good outcome independent of age, severity of left ventricular dysfunction, renal function, sodium levels, drug use, and co-morbidities. Indeed, other likely protective variables, such as good mobility (HR 0.91) or appropriate medication were not significant predictors in the multivariate model.

However, results from the second analysis showed that actually being recruited into a clinical trial was not predictive of outcome. “We found no appreciable difference in survival between those who are actually recruited to an interventional trial within the first year and those who were not,” says Dr Clark.

The investigators are unable to offer an obvious explanation for the findings, finding no systematic difference between their two study groups. They do, however, suggest that “being prepared to take part in a trial is a marker for better compliance with, and acceptance of, treatment”. They add that “patients’ attitudes to their illness and its treatment is an important aspect of their care”.

The study also highlighted the difference between real-life heart failure patients and those recruited to clinical trials - and this, say the investigators, may explain the difference seen in survival rates between the populations in clinical trials and those in everyday life. “Our study contributes to the perception that heart failure trials can be unrepresentative of real life,” says Dr Clark, “particularly as study designs often deliberately exclude patients with an inherently poor prognosis, such as those with anaemia or impaired renal function. Both these co-morbidities are common in real-life populations.”

NOTES:

1. Clark AL, Lammiman MJ, Goode, K, Cleland JGF. Is taking part in clinical trials good for your health? A cohort study. Eur J Heart Fail 2009; doi:10.1093/eurjhf/hfp133.
2. Cowie MR, Woods DA, Coats AJ, et al. Survival of patients with a new diagnosis of heart failure: a population based study. Heart 2000; 83: 505.
3. Wang O, Krumholz HM. Clinical trial participation: are we studying the patients we are trying to treat? Eur J Heart Fail 2009; doi:10.1093/eurjhf/hfp137.

Source: ESC Press Office

European Society of Cardiology

Stereotactic body radiation therapy (SBRT) should be considered a new standard of care for early-stage lung cancer treatment in patients with co-existing medical problems, according to results from a national clinical trial led by UT Southwestern Medical Center physicians.

In this study, 55 patients diagnosed with early non-small-cell lung (NSCL) cancer and unable to have their tumors surgically removed because of unrelated medical comorbidities were treated with SBRT during three noninvasive outpatient treatments.

The most recent findings, presented in Chicago at the 51st annual meeting of the American Society for Therapeutic Radiology and Oncology, show that the primary lung cancer did not recur 98 percent of the time. Despite their extreme frailty, more than half of these patients - 56 percent - were alive three years after diagnosis, while less than 20 percent ultimately died of metastatic lung cancer.

“These findings have changed the standard of care for lung cancer in patients with serious medical problems like emphysema, heart disease and strokes,” said Dr. Robert Timmerman, vice chairman of radiation oncology at UT Southwestern and principal investigator of the Radiation Therapy Oncology Group (RTOG) 0236 study.

SBRT delivers multiple high-dose radiation beams to a tumor in a concentrated, extremely precise manner. Each of these beams is relatively weak and causes very little damage when traveling through the patient’s body, but when all the beams converge at the target their cumulative effect delivers an extremely potent dose aimed at destroying the target cells with great precision.

“Despite the high potency of the treatment, less than 20 percent of these extremely frail patients experienced a serious health decline,” said Dr. Timmerman, considered one of the top international experts on stereotactic radiotherapy.

Dr. Timmerman said the study results were better than researchers had expected and are similar to the risks for healthier patients who undergo radical surgery - the standard treatment for early-stage NSCL cancer for the past century.

“The findings support the ongoing clinical research in healthier patients who currently undergo surgery for early-stage NSCL cancer,” Dr. Timmerman said. “SBRT is fast, convenient and very effective.”

Dr. Timmerman and his team, hoping to find out if the treatment indications might be expanded in a new trial, currently are conducting clinical studies using SBRT in healthier patients who would otherwise be candidates for surgery.

Participants are still being recruited for the study. To qualify, patients must have early-stage NSCL cancer but otherwise have no other medical problems.

Both studies are supported by the National Cancer Institute.

Source: Connie Piloto

UT Southwestern Medical Center

Human Genome Sciences (HGS) and GlaxoSmithKline (GSK) announced positive results from BLISS-76, the second of two large-scale phase III clinical trials of BENLYSTA™ (belimumab) for treating systemic lupus. A full presentation of results from BLISS-52 was recently shared at the 73rd Annual Scientific meeting of the American College of Rheumatology. Both trials succeeded in meeting their primary endpoints, which should make BENLYSTA eligible for approval by the U.S. Food and Drug Administration (FDA).

Both trials demonstrate that treatment with BENLYSTA plus standard of care was superior to that of placebo (inactive agent) plus standard of care. BENLYSTA significantly reduced disease activity. If approved by the FDA, BENLYSTA would be the first drug ever developed and approved specifically for the treatment of lupus.

Sandra C. Raymond, President and Chief Executive Officer of the Lupus Foundation of America (LFA) issued the following statement.

“We are truly excited to receive this groundbreaking news! Individuals with lupus and their families have waited more than 50 years to hear that it is possible to develop therapies that control the disease. We believe that this is a significant first step in developing the full arsenal of therapies and personalized treatment lupus requires.

“Conducting clinical trials in lupus has been extremely difficult due to many factors including the heterogeneity of the disease, the selection of appropriate clinical trial endpoints, and the confounding role of required background medications given to clinical trial participants. Human Genome Sciences and GlaxoSmithKline have proven that these barriers, while formidable, can be overcome.

“For decades the entire lupus research community has worked hard to better understand the causes and consequences of the disease. The fruits of that labor are starting to emerge. However, now is not the time for complacency. We must band together for lupus and continue to capitalize on the decades of research made possible through the efforts of the many dedicated researchers, physicians, people with lupus, and advocates.

“This announcement by HGS and GSK and the Overcoming Barriers to Drug Development in Lupus report, commissioned by the Lupus Foundation of America to outline recommendations on ways to overcome the barriers to lupus research, combine to serve as a call to action for a national coordinated effort to accelerate the pace of discovery, to develop more tolerable and effective treatments, and to ultimately find a cure for this perilous disease.

“We congratulate HGS and GSK on reaching this important milestone in lupus research and in the development of new therapies for lupus. We also extend our appreciation to the researchers and study volunteers who made this achievement possible: the physicians who have passionately committed to researching this disease, and the companies that continue to invest in finding new and necessary treatments for this devastating disease.”

The next step in the process is for HGS and GSK to submit marketing applications in the United States, Europe and other regions during the first half of 2010. The LFA will closely follow this process, and continue to keep its constituents apprised of developments.

Source
Lupus Foundation of America