Clinical trial NCT03924518: Adjunctive Granisetron Therapy in Patients With Sepsis or Septic Shock
Official title: Adjunctive Granisetron Therapy in Patients With Sepsis or Septic Shock：A Single-center, Randomized, Controlled, Single-blind Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sepsis
Keywords: sepsis
septic shock
granisetron
Lead sponsor: Zhujiang Hospital
Sponsor class: OTHER
First posted: 2019-04-23
Enrollment: 154
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The participants in treatment group receive intravenous granisetron. The participants in control group receive normal saline.
Primary purpose: TREATMENT

Brief 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

Eligibility criteria: Inclusion Criteria(Only patients who fully meet the following criteria are eligible to participate in the trial):

* Meets the diagnostic criteria for sepsis-3 developed by the American Society of Critical Care Medicine (SCCM)/European Critical Care Medicine Association (ESICM)
* Age ≥18 years old and age ≤80years old.
* Procalcitonin ≥2ng/ml

Exclusion Criteria:

* Age\<18 years, or age\>80 years.
* Pregnancy or lactating
* A solid-organ or bone marrow transplant patients.
* Patients with myocardial infarction within the past 3 months.
* Advanced pulmonary fibrosis .
* Patients with cardiopulmonary resuscitation before enrollment.
* HIV-positive patients.
* granulocyte-deficient patients.
* blood/lymphatic system tumors are not remission.
* patients with limited care (lack of commitment to full，aggressive life support).
* patients with long-term use of immunosuppressive drugs or with immunodeficiency.
* patients with advanced tumors.
* patients combined with non-infectious factors leading to the death(uncontrollable major bleeding, brain hernia, etc.).
* surgically unresolved infection sources(such as some intraperitoneal infection etc.)
* patients allergic to granisetron.
* patients with intestinal obstruction.

Primary outcomes:
measure: all-cause mortality rate
timeFrame: 28 days
Secondary outcomes:
measure: liver function(1)
timeFrame: Day at 1,2,3,4,5 after randomization
measure: liver function(2)
timeFrame: Day at 1,2,3,4,5 after randomization
measure: liver function(3)
timeFrame: Day at 1,2,3,4,5 after randomization
measure: liver function(4)
timeFrame: Day at 1,2,3,4,5 after randomization
measure: lung function
timeFrame: Day at 1,2,3,4,5 after randomization
measure: kidney function(1)
timeFrame: Day at 1,2,3,4,5 after randomization
measure: kidney function(2)
timeFrame: Day at 1,2,3,4,5 after randomization
measure: kidney function(3)
timeFrame: Day at 1,2,3,4,5 after randomization
measure: inflammatory response(1)
timeFrame: Day at 1,3,5 after randomization.
measure: inflammatory response(2）
timeFrame: Day at 1,3,5 after randomization.
measure: inflammatory response(3）
timeFrame: Day at 1,3,5 after randomization.
measure: inflammatory response(4）
timeFrame: Day at 1,3,5 after randomization.
measure: The level of lactic acid
timeFrame: Day at 1,2,3,4,5 after randomization
measure: immune function(1)
timeFrame: Day at 1, 3, 5 after randomization for test the the serum level of white blood cell(WBC).
measure: immune function(2)
timeFrame: Day at 1, 3, 5 after randomization for test the the serum level of lymphocyte.
measure: immune function(3)
timeFrame: Day at 1,5 after randomization for test the the serum level of CD4+ Tcell.
measure: immune function(4)
timeFrame: Day at 1, 5 after randomization for test the the serum level of CD8+Tcell.
measure: The level of 5-hydroxytryptamine (5-HT)
timeFrame: Day at 1,5 after randomization.
measure: Sequential Organ Failure Assessment (SOFA) score
timeFrame: Day at 1, 3, 5 after randomization
measure: The proportion of patients receiving mechanical ventilation
timeFrame: 28 days
measure: The proportion of patients receiving vasoactive drugs
timeFrame: 28 days
measure: The proportion of patients receiving renal replacement therapy(CRRT)
timeFrame: 28 days
measure: The duration of mechanical ventilation
timeFrame: 28 days
measure: The duration of vasoactive drugs
timeFrame: 28 days
measure: The duration of CRRT
timeFrame: 28 days
measure: ICU length of stay
timeFrame: 28 days
Other outcomes:
measure: Incidence of adverse events
timeFrame: 28 days
measure: Incidence of serious adverse events
timeFrame: 28 days
Locations:
city: Guangzhou
country: China
facility: Department of Critical Care Medicine of Zhujiang Hospital,Southern Medical University
state: Guangdong
Study officials:
affiliation: Department of Critical Care Medicine of Zhujiang Hospital
name: ping Chang, M.D.PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gong S, Yan Z, Liu Z, Niu M, Fang H, Li N, Huang C, Li L, Chen G, Luo H, Chen X, Zhou H, Hu J, Yang W, Huang Q, Schnabl B, Chang P, Billiar TR, Jiang Y, Chen P. Intestinal Microbiota Mediates the Susceptibility to Polymicrobial Sepsis-Induced Liver Injury by Granisetron Generation in Mice. Hepatology. 2019 Apr;69(4):1751-1767. doi: 10.1002/hep.30361. Epub 2019 Mar 5.
citation: Guan J, Guo Y, Chang P, Gan J, Zhou J, Wang H, Cen Z, Tang Y, Liu Z, Chen P. Adjunctive granisetron therapy in patients with sepsis or septic shock (GRANTISS): Study protocol for a randomized controlled trial. Medicine (Baltimore). 2019 Sep;98(39):e17354. doi: 10.1097/MD.0000000000017354.