Adjunctive Granisetron Therapy in Patients With Sepsis or Septic Shock
Condition: Sepsis
MeSH terms: Sepsis; Toxemia; Shock, Septic
Study type: Interventional
Phase: Phase 2

Summary: 
      In this prospective, single-center,randomized,controlled,single-blind clinical trial,Patients
      will be randomly assigned to receive granisetron or placebo for 4 days or until leaving the
      ICU(death or transfer from ICU to general ward or discharge). The primary outcome is
      all-cause death rate at 28 days.
    

Detailed description: 
      Investigational drug：Granisetron hydrochloride for injection

      Study title：Adjunctive Granisetron Therapy in Patients with Sepsis or Septic Shock:A
      Single-center,Randomized,Controlled,Single-blind Clinical trial.

      Principal Investigator：Professor Ping Chang ,Professor Zhanguo Liu, professor Peng
      Chen,Department of Critical Care Unit, Zhujiang Hospital, Southern Medical University

      Study subjects：Adult septic/septic shock patients with procalcitonin(PCT≥2ng/ml when entering
      the ICU.

      Study phase： Investigator Initiated Trial(IIT)

      Study objectives：The objective of the study is to determine whether granisetron, compared to
      placebo, improve the prognosis of sepsis or septic shock,including the reduction in
      mortality, the protection of organ function and reduction of inflammatory response,and to
      determine the safety of granisetron in patients with sepsis.

      Study design：A Single-center,Randomized,Controlled,Single-blind Clinical trial.

      Medication method： Granisetron treatment group： Follow the guidelines for sepsis in 2016 and
      recommend routine treatment + 3mg granisetron in 22 ml normal saline every 8 h for 4 days or
      until leaving the ICU(death or transfer from ICU to general ward or discharge), whichever
      come first.

      Placebo control group：Follow the guidelines for sepsis in 2016 and recommend routine
      treatment + 25ml normal saline every 8 h for 4 days or until leaving the ICU(death or
      transfer from ICU to general ward or discharge), whichever come first.

      Course：4days

      Sample size：154.

      Sites：1

      Primary endpoint：all-cause death at 28 days

      Secondary endpoints:

        1. The state of liver function: the serum level of transaminase(AST、ALT)、total
           bilirubin、direct bilirubin at 1,2,3,4,5 days after randomization

        2. The state of lung function:oxygenation index(PaO2/FiO2) at 1,2,3,4,5 days after
           randomization (the patients treated with extracorporeal membrane oxygenation will not
           collect this indicator).

        3. The state of kidney function:serum level of Creatinine (Cr)、blood urea
           nitrogen(BUN)、Cystatin(Cys) at 1,2,3,4,5 days after randomization

        4. The state of inflammatory response:the serum level of interleukin-6(IL-6) 、C-reactive
           protein 、Superoxide dismutase(SOD) and erythrocyte sedimentation rate(ESR) at 1,3,5 days
           after randomization.

        5. The state of circulation system: the serum level of lactic acid at 1,2,3,4,5 days after
           randomization

        6. The state of immune function:the serum level of white blood cell(WBC)、lymphocyte at 1,
           3, 5 days after randomization,the serum level of cluster of differentiation 4 Tcell(CD4+
           Tcell) and cluster of differentiation 8 Tcell(CD8+ Tcell) at 1,5days after
           randomization.

        7. The level of plasma 5-hydroxytryptamine(5-HT) at 1,5 days after randomization.

        8. Organ dysfunction assessed by Sequential Organ Failure Assessment (SOFA) score at 1, 3,
           5 after randomization

        9. Incidence and duration of supportive care for organ dysfunction including vasoactive
           agents, mechanical ventilation, continuous renal replacement therapy(CRRT)、daily
           condition of fuid balance

       10. The length of stay in ICU

      Safety endpoints：

        1. adverse events

        2. Serious adverse events
    

Intervention name(s): Granisetron Hydrochloride; Placebo（Normal saline）
Intervention type(s): Drug; Drug
Intervention description(s): Granisetron will be diluted with 0.9% saline to ensure that the therapeutic drug and placebo are identical in appearance, and 50 ml syringes will serve as the containers for all intravenous drugs.; therapeutic drug and placebo are identical in appearance, and 50 ml syringes will serve as the containers for all intravenous drugs.
Other intervention name(s): Selective 5-hydroxytryptamine 3 receptor inhibitor; 0.9% saline
Intervention MeSH terms: Granisetron; Serotonin
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: The participants in treatment group receive intravenous granisetron. The participants in control group receive normal saline.
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: sepsis; septic shock; granisetron