From "BPI in Patients with Hemorrhage Due to Trauma: Results of a
Multicenter Phase II Clinical Trial"
"the sample size was determined on the basis of previous reported work suggesting that in the placebo-treated group the incidence of serious complications or death would be approximately 50%. To detect a reduction to 35% with rBPI21 treatment, 400 patients (200 in each treatment group were required (80% power, alpha 0.05 two sided (two tailed))."
Efficacy Results:
"Pneumonia was the most common complication through day 15: 28% in the placebo group vs 20% in the rBPI group p = 0.07"
the composite " The proportion of patients who developed either pneumonia or ARDS was 32% in the placebo group vs 22% in the rBPI21
group post hoc p = 0.03"
Post hoc means that they did not initially planned for this "composite" so the result is not as strong as could be. But this is one of the reason that the phase III the pneumonia/ARDS combo is very well planned for (wise guys). It does make sense since ARDS is many time secondary to infections.
"Antibiotic use was similar between treatment groups"
Exclusion criteria: 16 exclusion criteria (How could they manage to recruit even one patient?) the end population was a very homogeneous one, but for age (from 18 to 75 years, median 33, 31). One of the exclusion criteria: weight more than 120 kilos. The subjects were in general good health before problems. These makes better to detect real differences and to avoid wide ranges of problems, it is more difficult to recruit and conduct the study.
" the number of days alive and out of the hospital, out of the intensive care unit, and off the ventilator during the 29 day study period were not different for the two treatment groups". This is not the result one wants to repeat, it takes argument out from approval and for pricing. This hemorragic/trauma is a tough problem, it does prevent infections but..., kind of the E5 problem, going for a fairly defined goal, but not entirely focus to infections, some luck or several thousands of patients to proof the point needed, or bpi is the best drug ever, or their faith is great. Facts are not so hot in this trauma subject. But if good results, means $billions.
I prefer the phase II in abdominal infections, good focus, straight infections vs infections, not blood loss / trauma / maybe infections / pneumo-ards combo. Too complex. Well Corr got away with it (and 10,000 patients recruited).
Finally from the DISCUSSION section:
"post hoc analysis revealed that the incidence of gram negative pneumonia and the composite incidence of pneumonia or ARDS was lower among rBPI21 treated than placebo-treated patients."
"The reduction in incidence of pneumonia or ARDS was especially pronounced in patients with penetrating injury but was also observed in patients with blunt injury." kind of obvious, but fact is good.
"These results of the rate of pneumonia/ARDS must be interpreted with caution because, althoug both were components of the primary end point, the composite rate of pneumonia/ARDS was not a PRESPECIFIED end point and patients were not randomized by type of injury."
For phase III they are going to clearly PRESPECIFIED the prevention of the combo as a composite pneumonia/ARDS and the type of injury blunt vs penetrating vs placebo. Much more focus.
They should go for 3,000 patients.
Meningo trial should go for 800. |
