Why Part A?
Carefully designed studies conducted over the last 20 years have shown that treatment with the clot-dissolving drug rtPA, commenced within three hours after the onset of symptoms, improves the chances of surviving a stroke without disability. Regulatory agencies have approved rtPA to be used at a dose of 0.9 mg per kilogram of body weight.
Subsequent research studies have confirmed benefits of rtPA in patients of different ages and in different populations, when used up to four and a half hours after the onset of ischaemic stroke. However, research in the last 10 years suggests that a slightly lower dose of rtPA – 0.6 mg per kilogram body weight – is equally effective and possibly even safer in terms of the risk of brain haemorrhage.
As most of this research has been conducted in Japan, low-dose rtPA (0.6 mg/kg) is the standard approved treatment for acute ischaemic stroke in that country. One hypothesis is that Japanese people, and possibly other Asian people, are more sensitive to rtPA than Caucasian people, but another explanation is that the dose of rtPA depends on the size of the clot in the brain causing the stroke. Examination of blood vessels in the brain during administration of rtPA has shown that most clots dissolve quickly after the injection of rtPA, that is before the full dose is given over an hour.
However, as there have been no carefully designed research studies to compare between patients who have received the 0.9 mg/kg and 0.6 mg/kg doses of rtPA, we do not know which of the two doses is the best and safest. Also, given that rtPA is an expensive drug, which costs between $1000 and $2000 in most countries around the world, there are significant financial gains for patients, doctors and governments responsible for health care in knowing whether the 0.6 mg/kg dose, which costs less, is ‘equally good’ or ‘better’, or possibly ‘worse’, than the 0.9 mg/kg dose.