Racecadotril for Organ Injury in Sepsis Patients

Racecadotril for Organ Injury in Sepsis Patients: A Single-Center, Single-Blind, Randomized, Placebo-Controlled Pilot Trial

In this single-center, single-blind, randomized, placebo-controlled pilot trial. The effect of Racecadotril on the improvement of organ function will be investigated in patients with sepsis. Researchers will screen patients admitted to the Department of Critical Care Medicine at Zhujiang Hospital to identify patients with sepsis based on including and excluding criteria and obtain informed consent and randomize them into groups.

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 20ml of water for nasal feeding tube,three times daily. The changes in SOFA-2 score and other clinically meaningful outcomes in 4 days will be collected. For subjects whose treatment lasts less than 4 days, the changes on the date of ICU discharge will be used.

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:

1. 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:

1. 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.
2. The state of liver function: the serum level of transaminase (AST and ATL) and total bilirubin at 96 h after first treatment administration.
3. 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.
4. 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.
5. 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.
6. 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.
7. The state of infection: the serum level of procalcitonin (PCT) at 96 h after first treatment administration.
8. The organ function support status: mechanical ventilation, RT treatment status, ECMO support status at 96 h after first treatment administration.
9. The critical score: APAPCHE II score at 96 h after first treatment administration.

Safety endpoints:

1. Safety evaluation indicators: Possible adverse reactions of Racecadotril may include (drowsiness, rash, constipation, nausea, abdominal pain), survival status on the 28th day.
2. 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:

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

Exclusion Criteria:

1. Patients with a known allergy to the study product.
2. Patients unable to receive enteral nutrition via a gastrointestinal tube.
3. Patients with hepatic insufficiency: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels both greater than 3 times the upper limit of normal.
4. Patients with renal dysfunction: Acute kidney injury (AKI) ; chronic kidney disease (CKD) stage 3 or higher.
5. 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).
6. Patients with fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase deficiency.
7. Pregnant or breastfeeding women.
8. Patients with limited nursing care (patients for whom active treatment has been withdrawn).