Effectiveness of anisodamine for the treatment of critically ill patients with septic shock (ACIdoSIS study): study protocol for randomized controlled trial

Abstract

Background: Septic shock is an important contributor of mortality in the intensive care unit (ICU). Although strenuous effort has been made to improve its outcome, the mortality rate is only marginally decreased. The present study aimed to investigate the effectiveness of anisodamine in the treatment of septic shock, in the hope that the drug will provide alternatives to the treatment of septic shock.

Methods: The study is a multi-center randomized controlled clinical trial. Study population will include critically ill patients with septic shock requiring vasopressor use. Blocked randomization was performed where anisodamine and control treatments were allocated at random in a ratio of 1:1 in blocks of sizes 2, 4, 6, 8, and 10 to 354 subjects. Interim analysis will be performed. The primary study end point is the hospital mortality, and other secondary study endpoints include ICU mortality, length of stay in ICU and hospital, organ failure free days. Adverse events including new onset psychosis, urinary retention, significant hypotension and tachycardia will be reported.

Discussion: The study will provide new insight into the treatment of septic shock and can help to reduce mortality rate of septic shock.

Trial registration: NCT02442440 (https://register.clinicaltrials.gov/).

Keywords: Anisodamine; intensive care unit (ICU); mortality; randomized controlled trial; septic shock.

Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

Figures

Figure 1

Spending futility and efficacy boundaries for sequential trial analysis. Trial will stop at crossing either boundaries.

Figure 2

Cumulative probability of crossing boundary by different relative risks. Upper boundary indicates futility boundary and the lower boundary indicates efficacy boundary.

Figure 3

Risk difference at bounds. It is shown that if the first analysis performed at accrual of 61 subjects shows a risk difference of more than 0.42, the study can be stopped for superiority of anisodamine.

Figure 4

Expected sample size by underlying different risk difference. It is shown that if the risk difference is extremely large or small the sample size required can be small. At the assumed risk difference of 0.15, the expected sample size is 260, which is smaller than the fixed sample size of 339.