Adjunctive granisetron therapy in patients with sepsis or septic shock (GRANTISS): A single-center, single-blinded, randomized, controlled clinical trial

Abstract

Background: In preclinical experiments, we demonstrated that the 5-HT3 receptor antagonist granisetron results in reduced inflammation and improved survival in septic mice. This randomized controlled trial was designed to assess the efficacy and safety of granisetron in patients with sepsis.Methods: Adult patients with sepsis and procalcitonin ≥ 2 ng/ml were randomized in a 1:1 ratio to receive intravenous granisetron (3 mg every 8 h) or normal saline at the same volume and frequency for 4 days or until intensive care unit discharge. The primary outcome was 28-day all-cause mortality. Secondary outcomes included the duration of supportive therapies for organ function, changes in sequential organ failure assessment scores over 96 h, procalcitonin reduction rate over 96 h, the incidence of new organ dysfunction, and changes in laboratory variable over 96 h. Adverse events were monitored as the safety outcome.Results: The modified intention-to-treat analysis included 150 septic patients. The 28-day all-cause mortalities in the granisetron and placebo groups were 34.7% and 35.6%, respectively (odds ratio, 0.96; 95% CI, 0.49–1.89). No differences were observed in secondary outcomes. In the subgroup analysis of patients without abdominal or digestive tract infections, the 28-day mortality in the granisetron group was 10.9% lower than mortality in the placebo group. Adverse events were not statistically different between the groups.Conclusion: Granisetron did not improve 28-day mortality in patients with sepsis. However, a further clinical trial targeted to septic patients without abdominal/digestive tract infections perhaps is worthy of consideration.

Clinical Efficacy of Megadose Vitamin C in Sepsis: Protocol for a Multicenter Randomized Single-Blind Placebo-Controlled Clinical Trial

“…Based on the exploratory analysis outcome of the CITRIS-ALI trial, we expected that the relative risk of mortality between the intervention and control groups would be 0.49 [10]. Based on the clinical experience of our centers, the average mortality of patients with sepsis in the control group is approximately 34.7% [17]. Therefore, the estimated average mortality of patients in the intervention group is calculated as follows: 34.7% × 0.49 = 17.003%.…”

Quality by Design Approach for Development and Characterization of Granisetron Hydrochloride-Loaded Orodispersible Films

“…Additionally, granisetron has a strong performance in terms of drug safety, allowing the application on children over 2 years old and patients aged 65 years or older. 4 5 6 Nevertheless, marketed pharmaceutical products still encounter challenges concerning patient compliance. Injections need to be administered by professional medical staff.…”