Adjunctive Granisetron Therapy in Patients With Sepsis or Septic Shock:A Single-center, Randomized, Controlled, Single-blind Clinical Trial

Adjunctive Granisetron Therapy in Patients With Sepsis or Septic Shock

Sponsors

Lead sponsor: Zhujiang Hospital

Source 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

Overall Status Recruiting
Start Date April 25, 2019
Completion Date December 31, 2020
Primary Completion Date December 31, 2020
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
all-cause mortality rate 28 days
Secondary Outcome
Measure Time Frame
liver function(1) Day at 1,2,3,4,5 after randomization
liver function(2) Day at 1,2,3,4,5 after randomization
liver function(3) Day at 1,2,3,4,5 after randomization
liver function(4) Day at 1,2,3,4,5 after randomization
lung function Day at 1,2,3,4,5 after randomization
kidney function(1) Day at 1,2,3,4,5 after randomization
kidney function(2) Day at 1,2,3,4,5 after randomization
kidney function(3) Day at 1,2,3,4,5 after randomization
inflammatory response(1) Day at 1,3,5 after randomization.
inflammatory response(2) Day at 1,3,5 after randomization.
inflammatory response(3) Day at 1,3,5 after randomization.
inflammatory response(4) Day at 1,3,5 after randomization.
The level of lactic acid Day at 1,2,3,4,5 after randomization
immune function(1) Day at 1, 3, 5 after randomization for test the 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.
immune function(3) Day at 1,5 after randomization for test the 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 level of 5-hydroxytryptamine (5-HT) Day at 1,5 after randomization.
Sequential Organ Failure Assessment (SOFA) score Day at 1, 3, 5 after randomization
The proportion of patients receiving mechanical ventilation 28 days
The proportion of patients receiving vasoactive drugs 28 days
The proportion of patients receiving renal replacement therapy(CRRT) 28 days
The duration of mechanical ventilation 28 days
The duration of vasoactive drugs 28 days
The duration of CRRT 28 days
ICU length of stay 28 days
Enrollment 154
Condition
Intervention

Intervention type: Drug

Intervention name: Granisetron Hydrochloride

Description: 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.

Arm group label: granisetron group

Other name: Selective 5-hydroxytryptamine 3 receptor inhibitor

Intervention type: Drug

Intervention name: Placebo(Normal saline)

Description: therapeutic drug and placebo are identical in appearance, and 50 ml syringes will serve as the containers for all intravenous drugs.

Arm group label: placebo group

Other name: 0.9% saline

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.

Gender: All

Minimum age: 18 Years

Maximum age: 80 Years

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
ping Chang, M.D.PhD Principal Investigator Department of Critical Care Medicine of Zhujiang Hospital
Overall Contact

Last name: zhanguo Liu, M.D.PhD

Phone: +86-2062782927

Email: [email protected]

Location
facility status contact Department of Critical Care Medicine of Zhujiang Hospital,Southern Medical University ping Chang, PhD
Location Countries

China

Verification Date

April 2019

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: granisetron group

Arm group type: Experimental

Description: 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.

Arm group label: placebo group

Arm group type: Placebo Comparator

Description: 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.

Acronym GRANTISS
Patient Data No
Study Design Info

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.

Primary purpose: Treatment

Masking: Double (Participant, Outcomes Assessor)

Source: ClinicalTrials.gov