Intraventricular TPA for intraventricular hemorrhage - I wouldn't call it counter-intuitive, but I would certainly call it unusual.
This is a small placebo-controlled, randomized, blinded, prospective trial enrolling 48 patients with intraventricular hemorrhage requiring placement of an intraventricular catheter for CSF drainage. They were testing the theory that low-dose TPA would assist in clot breakdown, thus speeding recovery. There are probably not significant differences between groups - although the placebo group was oddly mostly women. Also fascinatingly, the predicted mortality of each group was ~74% - and ended up being 23% in the placebo group and 19% in the TPA group. Serious adverse events including 61% in the TPA group and 36% in the TPA group. Due to the small sample size of the cohort, none of these differences reached statistical significance.
Unfortunately, the screaming major flaw in this study is that they do not truly have a control group - a true control would be standard care without the use of placebo administration through the intraventricular catheter. Their rate of ventriculitis (8% and 9%) is higher than the typically expected rate for intraventricular catheter placement (probably below 5%), and is consistent with prior studies that showed increased incidence of ventriculitis when the catheter is used for administration of drugs or irrigation. So, the safety profile and minimal outcome trend in favor of the TPA group can't truly be evaluated because it isn't being compared to the current standard of care, which is leaving the catheter alone for drainage only.
The authors conclude these results support further evaluation - which is already ongoing in the CLEAR III trial - and that the treatment met their pre-defined safety profile cut-offs. Unfortunately, yet again, propagating their skew on the data is motivated by financial interests - Johns Hopkins has applied for a use patent and Genentech is behind the rtPA licensing and funding.
"Low-Dose Recombinant Tissue-Type Plasminogen Activator Enhances Clot Resolution in Brain Hemorrhage"