Racecadotril for Organ Injury in Sepsis Patients

Investigational drug: Racecadotril Granules Study title: Racecadotril for Organ Injury in Sepsis Patients: A Single-Center, Single-Blind, Randomized, Placebo-Controlled Pilot Trial Principal Investigator: Zhanguo Liu, professor, Department of Critical Care Medicine, Zhujiang Hospital, Southern Medical University Study subjects: Patients diagnosed with sepsis according to the SOFA-2 scoring criteria published by JAMA in 2025 (PMID: 41159833).

Study objectives: The objective of the study is to determine whether Racecadotril, compared to placebo, improves organ dysfunction scores (SOFA -2 scores) in septic patients.

Study design: A single-center, single-blind, randomized, placebo-controlled pilot trial.

Method: On the basis of standardized treatment for sepsis, the Racecadotril group will be given Racecadotril Granules at a dose of 1.5mg/kg reconstituted in 20ml of water for nasal feeding tube, three times daily; the Control group will be given an equal volume of water for nasal feeding tube,three times daily, intervention for 4 days or until ICU discharge(whatever come first).

Course: 4 days Sample size: 44 The number of study center: 1

Study center:

• Department of Critical Care Medicine of Zhujiang Hospital,Southern Medical University,Guangzhou, China Primary endpoint: 96-hour Sequential Organ Failure Assessment-2 (SOFA-2) score

Secondary endpoints:

• The blood routine examination: White blood cell count, neutrophil count, neutrophil ratio, lymphocyte count, lymphocyte ratio, platelet count at 96 h after first treatment administration.
• The state of liver function: the serum level of transaminase (AST and ATL) and total bilirubin at 96 h after first treatment administration.
• The state of kidney function: the serum level of Creatinine (Cr)#blood urea nitrogen (BUN)# and daily urine output at 96 h after first treatment administration.
• The state of circulation system: Blood pressure, the duration and dosage of vasopressor drugs, and the serum level of lactate at 96 h after first treatment administration.
• The state of lung function: oxygenation index(PaO2/FiO2), partial pressure of oxygen, partial pressure of carbon dioxide at 96 h after first treatment administration.
• The state of inflammatory response: the serum level of interleukin-6(L-6) and C-reactive protein (CRP) at 96 h after first treatment administration.
• The state of infection: the serum level of procalcitonin (PCT) at 96 h after first treatment administration.
• The organ function support status: mechanical ventilation, RT treatment status, ECMO support status at 96 h after first treatment administration.
• The critical score: APAPCHE II score at 96 h after first treatment administration.

Safety endpoints:

• Safety evaluation indicators: Possible adverse reactions of Racecadotril may include (drowsiness, rash, constipation, nausea, abdominal pain), survival status on the 28th day.
• Feasibility evaluation indicators: Record the specific number of days and times that patients used Racecadotril; ICU hospitalization days.

For subjects whose treatment lasts less than 4 days, the changes on the date of ICU discharge will be used.

Inclusion criteria

• diagnosed with sepsis according to the SOFA-2 scoring criteria published in 2025 JAMA(PMID:41159833);
• SOFA-2 score: 6 - 14 points;
• subjects who voluntarily participated in this study and signed an informed consent form.
• age 18 - 80 years.

Exclusion criteria

• Patients with a known allergy to the study product.
• Patients unable to receive enteral nutrition via a gastrointestinal tube.
• Patients with hepatic insufficiency: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels both greater than 3 times the upper limit of normal.
• Patients with renal dysfunction: Acute kidney injury (AKI) ; chronic kidney disease (CKD) stage 3 or higher.
• Patients receiving medications at the start of the study that may significantly interfere with the pharmacodynamics and metabolism of Racecadotril, or increase its toxicity(Such as Erythromycin, Ketoconazole, Rifampicin).
• Patients with fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase deficiency.
• Pregnant or breastfeeding women.
• Patients with limited nursing care (patients for whom active treatment has been withdrawn).