Attached
Our previous studies showed that platelet activating factor (PAF)
was a potent mediator of vascular leak. Therefore, we proceeded to
investigate the efficacy of rupatadine which is a PAF receptor blocker in
patients with acute dengue infection. We conducted a phase II, open
label, randomized placebo controlled trial to determine the safety of
rupatadine in patients with acute dengue, the efficacy of rupatadine
in preventing or reducing vascular leak and to determine its efficacy in
reducing complications associated with acute dengue. The study was
carried out in 3 arms: rupatadine 40mg daily, rupatadine 10mg daily and
the placebo. The patients were examined and laboratory parameters
were measured at least twice a day to detect any complications and fluid
leakage. Daily ultrasound scans were done from the day of admission to
determine the presence and the quantity of fluid leakage. 138 patients
were recruited on day 4.8 of illness (SD±0.55) with 44 receiving 40mg
daily rupatadine, 44 receiving 10mg daily rupatadine and 44 receiving
placebo. Both rupatadine 10mg and 40mg were found to be safe and did
not cause any increase in adverse effects when compared to the placebo.
The proportion of individuals who developed either pleural effusions or
ascites (22.7%), were similar in all 3 arms. None of the patients given
rupatadine 40mg developed bleeding manifestations, while 2 (4.5%)
in the 10mg and 5 (11.4%) in the placebo arms developed significant
bleeding manifestations. None of the patients in the rupatadine 40mg arm
developed organ dysfunction, while 1 (2.3%) patient in 10mg arm and
3 patients (6.8%), in the placebo arm developed liver dysfunction. Those
given rupatadine 40mg daily had less reduction in the platelet counts
and less elevation of liver transaminases when compared to the 10mg
rupatadine and the placebo arm. Rupatadine appears to be safe in patients
with acute dengue infection. Although rupatadine did not reduce the
proportion of individuals who develop fluid leakage when given on day
4-5 of illness, it appears to reduce complications associated with dengue.
However, it will be important to confirm these findings in larger studies.
