Adjunctive Granisetron Therapy in Patients With Sepsis or Septic Shock
- Conditions
- Sepsis
- Interventions
- Drug: Placebo（Normal saline）
- Registration Number
- NCT03924518
- Lead Sponsor
- Zhujiang Hospital
- 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 154
Not provided
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description granisetron group Granisetron Hydrochloride 3ml granisetron（3mg） will be diluted in 22 mL of 0.9% normal saline,and the granisetron diluted will be intravenously injected for at 10 minutes， every 8 hours for 4 days or until leaving the ICU(death or transfer from ICU to general ward or discharge), whichever come first. placebo group Placebo（Normal saline） Normal saline 25ml every 8h for 4 days or until leaving the ICU(death or transfer from ICU to general ward or discharge), whichever come first.
- Primary Outcome Measures
Name Time Method all-cause mortality rate 28 days All-cause mortality rate from the enrollment to the 28th days
- Secondary Outcome Measures
Name Time Method liver function(3) Day at 1,2,3,4,5 after randomization the serum level of total bilirubin
The level of 5-hydroxytryptamine (5-HT) Day at 1,5 after randomization. The level of plasma 5-HT
The proportion of patients receiving mechanical ventilation 28 days The proportion of patients receiving mechanical ventilation within 28 days after randomization
liver function(1) Day at 1,2,3,4,5 after randomization the serum level of Alanine transaminase(ALT)
kidney function(1) Day at 1,2,3,4,5 after randomization serum level of Creatinine (Cr)
The duration of mechanical ventilation 28 days The the duration of mechanical ventilation therapy in hours( This outcome measure is intended only for patients receiving mechanical ventilation)
lung function Day at 1,2,3,4,5 after randomization oxygenation index(PaO2/FiO2)，the patients treated with extracorporeal membrane oxygenation will not collect this indicator
kidney function(3) Day at 1,2,3,4,5 after randomization serum level of Cystatin(Cys)
inflammatory response(4） Day at 1,3,5 after randomization. the serum level of erythrocyte sedimentation rate(ESR)
inflammatory response(3） Day at 1,3,5 after randomization. the serum level of superoxide dismutase(SOD)
The level of lactic acid Day at 1,2,3,4,5 after randomization the serum level of lactic acid
ICU length of stay 28 days ICU length of stay
liver function(2) Day at 1,2,3,4,5 after randomization the serum level of Aspartate transaminase (AST)
liver function(4) Day at 1,2,3,4,5 after randomization the serum level of direct bilirubin
kidney function(2) Day at 1,2,3,4,5 after randomization serum level of blood urea nitrogen(BUN)
inflammatory response(1) Day at 1,3,5 after randomization. the serum level of interleukin-6(IL-6)
immune function(3) Day at 1,5 after randomization for test the the serum level of CD4+ Tcell. the serum level of CD4+ Tcell
immune function(4) Day at 1, 5 after randomization for test the the serum level of CD8+Tcell. the serum level of CD8+Tcell
The proportion of patients receiving vasoactive drugs 28 days The proportion of patients receiving vasoactive drugs within 28 days after randomization
The proportion of patients receiving renal replacement therapy(CRRT) 28 days The proportion of patients receiving CRRT within 28 days after randomization
The duration of CRRT 28 days The the duration of CRRT therapy in hours( This outcome measure is intended only for patients receiving CRRT)
inflammatory response(2） Day at 1,3,5 after randomization. the serum level of C-reactive protein(CRP)
immune function(1) Day at 1, 3, 5 after randomization for test the the serum level of white blood cell(WBC). the serum level of white blood cell(WBC)
immune function(2) Day at 1, 3, 5 after randomization for test the the serum level of lymphocyte. the serum level of lymphocyte
The duration of vasoactive drugs 28 days The the duration of vasoactive drugs therapy in hours( This outcome measure is intended only for patients receiving vasoactive drugs)
Sequential Organ Failure Assessment (SOFA) score Day at 1, 3, 5 after randomization Organ dysfunction assessed by Sequential Organ Failure Assessment (SOFA) score.SOFA score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems.The highest score for each of the six items is 4 points, and the lowest score is 0 points.Finally, the scores of the six items are summed to get the value of the sofa score.The range of the sofa score is 0-24.Higher values represent a worse outcome.
Trial Locations
- Locations (1)
Department of Critical Care Medicine of Zhujiang Hospital,Southern Medical University
🇨🇳Guangzhou, Guangdong, China