Activated protein C in sepsis: an Indian experience

Background

The PROWESS study has shown that the use of recombinant human activated protein C (rhAPC) can reduce mortality in severe sepsis [1]. The effect of this novel drug in a Third World setting has never been explored. The aim of this study is to see whether all the end points of the PROWESS study could be reproduced in the Indian population.

Method

A prospective, single-center observational study. Consecutive patients who fulfilled the inclusion criteria of the PROWESS study [1] were included into the study. The study group was patients who received rhAPC. Patients who did not receive rhAPC formed the control group. Data collected were demographics, details of premorbid conditions and organ function, markers of disease severity and infection. APACHE II scores were recorded at baseline. Organ dysfunction was measured using SOFA scoring. The primary end point was all-cause mortality at 28 days. Secondary end points were morbidity as measured by SOFA scores and the incidence of adverse events. Data are expressed as mean ± standard deviation. The results were analysed using Fisher's exact test and unpaired t tests. P < 0.05 was considered significant.

Results

A total of 25 patients were enrolled into the study (study group – 14 and controls – 11). Both groups were similar in terms of age and sex distribution, demographics, comorbidities, baseline APACHE II score, ventilatory and inotropic support and number of organ dysfunction. In the study group only 27% had an APACHE II score > 25. Treatment with rhAPC was started at a mean of 34.9 ± 21.9 hours from the onset of first organ dysfunction or admission, whichever occurred earlier. The 28-day mortality in our study was 36% in the study group as compared with 64% in the controls. This was not statistically significant. There was an improvement in the SOFA score on day 7 in 57% of the study group and 36% of controls. The only adverse event noted was bleeding. Minor bleeding was seen in 64% of the study group, which was significantly higher than that in 18% of controls.

Conclusion

This study is not powered to come to any definitive conclusion. There was a trend towards decreasing mortality in patients treated with rhAPC as compared with the controls and there was also a decrease in morbidity in the study group as assessed by the SOFA scores. The incidence of bleeding, even though minor, was significantly higher in the study group. However, unlike in the PROWESS study, only 27% of the study group had an APACHE II score > 25 despite 43% of them having three or more organ system failures. This brings up the question of whether the APACHE II score can be used as a marker of severity of illness in the Indian population? The high cost of the drug is a concern in the Indian setting where most patients rely on their own resources for funding such drugs. The only way these questions can be answered is by having a well-designed and powered study conducted in the Indian population.