People infected with the H5N1 bird flu virus are now prescribed the standard dose of Tamiflu, which is one capsule twice daily for five days.
But less than half the patients survive.
Tawee Chotpitayasunondh, senior medical officer at Thailand's Ministry of Public Health, said: "In animal studies, higher doses of Tamiflu have resulted in higher cure rates for H5N1.
"The death rate from H5N1 is 60 per cent, we want to see if we can solve this problem".
Indonesia, Thailand, Vietnam and the United States will participate in the Tamiflu clinical trial.
All bird flu victims will be included in the trial and each country will pick 100 patients suffering from severe human flu.
In both categories, half of the participants will be given the standard Tamiflu dosage, while the other half will be given double doses, or 150 mg orally, twice daily for 10 days.
Severe human flu cases would be included because some symptoms and complications were similar to H5N1, such as pneumonia.
"We'll find out if it is safe to give double dose," Doctor Tawee said.
Concerns over Tamiflu
For the moment, there are no commercially available vaccines against the H5N1 virus and Tamiflu is regarded as the best front-line defence against the disease if given to a patient during the early onset of symptoms.
Many nations have stockpiled the drug in the event of a bird flu pandemic.
News of the trial comes after growing concerns Tamiflu could induce psychiatric symptoms.
Japan warned doctors this week not to give Tamiflu to young people, after two teenagers fell from buildings after taking it.
"We are concerned about the cases in Japan, but Japan consumes a lot of the total production of Tamiflu (for human flu). If you use a lot, you may have more side effects," Doctor Tawee said. "But we will closely monitor our subjects."
While H5N1 threatens mainly birds, experts fear it can trigger a pandemic once it learns to transmit efficiently among people. If it does, millions could die.