Gelaspan vs Crystalloid Therapy in Sepsis

Not Applicable

Not yet recruiting

• Conditions: Sepsis; Intra-Abdominal Infections
• Interventions: Drug: Balanced Gelatin Solution; Drug: Acetate Ringer's Solution

• Registration Number: NCT07172451
• Lead Sponsor: Shanghai Zhongshan Hospital

Brief Summary

The goal of this clinical trial is to evaluate whether balanced gelatin solution is effective and safe for perioperative fluid management in adult patients with sepsis undergoing emergency abdominal surgery.

The main questions it aims to answer are:

Does balanced gelatin solution improve fluid balance within 24 hours after surgery compared with crystalloid solution? Does balanced gelatin solution increase the proportion of patients who achieve hemodynamic stability within 24 hours after surgery? Researchers will also examine secondary outcomes including kidney function, organ dysfunction, postoperative complications, mortality, and length of ICU and hospital stay.

Participants will:

Receive either balanced gelatin solution or crystalloid solution during surgery according to a goal-directed hemodynamic protocol.

Be followed for outcomes up to 90 days after surgery.

Detailed Description

Sepsis is a life-threatening condition characterized by organ dysfunction caused by a dysregulated host response to infection. Despite advances in recognition and management, mortality remains high, ranging from 18% to 30%. A cornerstone of treatment is timely and effective fluid resuscitation. Current international guidelines recommend rapid administration of at least 30 mL/kg of crystalloids within the first hours of diagnosis, followed by continued resuscitation guided by hemodynamic parameters. However, the optimal type of resuscitation fluid remains uncertain.

Crystalloids are inexpensive and widely available but rapidly distribute into the interstitial space, particularly in patients with increased vascular permeability, leading to tissue edema and impaired microcirculation. Colloids, in contrast, contain large molecules that exert colloid osmotic pressure and help retain water within the intravascular space, potentially maintaining higher capillary perfusion pressure and improving microcirculatory blood flow. Among artificial colloids, hydroxyethyl starch is no longer recommended due to increased risk of kidney injury and mortality, and albumin is limited by cost and supply. Gelatin, derived from bovine collagen, is currently the only synthetic colloid recommended by guidelines for use in sepsis-induced hypovolemia. Nevertheless, high-quality clinical evidence regarding its efficacy and safety in septic patients undergoing surgery remains lacking.

This study focuses on balanced gelatin solution, a compound preparation consisting of 4% succinylated gelatin in a balanced electrolyte solution. The central hypothesis is that balanced gelatin solution may provide more efficient plasma volume expansion, reduce positive fluid balance, stabilize hemodynamics, improve microcirculatory perfusion, and ultimately enhance organ function recovery and clinical outcomes compared with crystalloid solution alone.

Objectives The primary objectives are to evaluate whether balanced gelatin solution reduces fluid overload, increases the proportion of patients achieving hemodynamic stability, and improves microcirculatory perfusion in septic patients undergoing emergency abdominal surgery. Secondary objectives include assessing the safety of balanced gelatin, particularly its effects on kidney function, coagulation, and postoperative complications.

Study Design This is a prospective, multicenter, randomized, double-blind, controlled clinical trial with an adaptive design incorporating sample size re-estimation. An initial sample size of 318 patients (159 per group) will be recruited, with an interim analysis after enrollment of 50% of participants to reassess the required sample size. Patients are randomized in a 1:1 ratio to receive either balanced gelatin or crystalloid solution (Ringer's acetate). Randomization is stratified by baseline blood lactate level (≤ 4 mmol/L vs \> 4 mmol/L) using a central dynamic allocation system to ensure balance between groups.

Population Eligible patients are adults (≥18 years) with sepsis (per Sepsis-3 criteria) due to abdominal infection requiring emergency surgery. Inclusion requires a SOFA score ≥2 and lactate \>2 mmol/L. Key exclusions include prior colloid use within 24 hours, expected death within 48 hours, advanced heart failure, severe ARDS, pre-existing renal replacement therapy, severe coagulopathy, liver failure, or allergy to gelatin.

Interventions All participants receive standardized anesthesia care. Intraoperative fluid therapy follows a goal-directed protocol guided by stroke volume monitoring. After randomization, patients in the intervention group receive balanced gelatin solution as the resuscitation fluid (maximum dose 30 mL/kg within 24 hours), while controls receive Ringer's acetate only. Both groups receive a baseline infusion of Ringer's acetate at 3 mL/kg/h during anesthesia. Vasoactive drugs are used according to predefined hemodynamic triggers. Postoperatively, the assigned fluid regimen is continued for 24 hours, after which fluid management follows routine clinical practice.

Endpoints

Primary endpoints include:

Cumulative fluid balance within 24 hours after surgery. Proportion of patients achieving hemodynamic stability within 24 hours. Secondary endpoints include kidney function, SOFA score dynamics, lactate clearance, need for vasopressors or renal replacement therapy, postoperative complications, ICU and hospital length of stay, and all-cause mortality at 28 and 90 days. Safety endpoints include fluid overload, pulmonary edema, arrhythmias, and acute kidney injury.

Follow-up Patients will be followed during hospitalization and by structured telephone interviews at day 28 and day 90. Follow-up assessments include survival, complications, and health-related quality of life using the EQ-5D-5L questionnaire.

Blinding and Oversight The study is double-blind: patients, treating clinicians, outcome assessors, and statisticians remain unaware of group allocation. Randomization and drug packaging are handled by independent, unblinded coordinators. Emergency unblinding is permitted only for patient safety. An independent Data and Safety Monitoring Board (DSMB) will oversee trial conduct and review adverse events.

Significance By directly comparing balanced gelatin with crystalloids in septic patients undergoing emergency abdominal surgery, this trial will provide critical evidence regarding the efficacy and safety of gelatin-based fluid resuscitation. Results are expected to inform perioperative fluid management strategies and contribute to guideline development in the management of sepsis.

Study Timeline

• Status Verified: 2025-09
• Study First Submitted: 2025-09-03
• Study First Submitted QC: 2025-09-10
• Last Update Submitted: 2025-09-10
• Study First Posted: 2025-09-15
• Last Update Posted: 2025-09-15
• Study Start: 2025-11-01
• Primary Completion: 2028-09-30
• Study Completion: 2028-12-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 318

Inclusion Criteria

• Age ≥18 years.
• Diagnosis of sepsis according to Sepsis-3 definition.
• Scheduled for emergency non-cardiac surgery under general anesthesia.
• Randomization and study intervention can be initiated before skin incision.
• Provision of written informed consent by patient or legal representative.

Exclusion Criteria

• Cardiac surgery, neurosurgery, or procedures requiring cardiopulmonary bypass.
• Severe preexisting cardiac dysfunction (ejection fraction <30%, NYHA class IV).
• End-stage renal disease requiring chronic renal replacement therapy.
• Known severe hepatic failure (Child-Pugh C).
• Known allergy or contraindication to study fluids (gelatin solution or crystalloid solution).
• Pregnant or lactating women.
• Participation in another interventional trial within the past 30 days.
• Life expectancy <24 hours or decision to withhold/withdraw life-sustaining treatment.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Balanced Gelatin Solution	Balanced Gelatin Solution	Patients randomized to the balanced gelatin group will receive balanced gelatin solution (4% succinylated gelatin in a balanced crystalloid carrier) as the primary resuscitation fluid during emergency abdominal surgery for sepsis. Fluid administration follows a goal-directed protocol guided by stroke volume monitoring. The maximum total volume of balanced gelatin is limited to 30 mL/kg (ideal body weight) within the intraoperative and first 24-hour postoperative period. If the limit is reached, additional resuscitation will be performed with balanced crystalloid solution.
Crystalloid Solution	Acetate Ringer's Solution	Patients randomized to the crystalloid group will receive acetate Ringer's solution as the sole resuscitation fluid during emergency abdominal surgery for sepsis, according to the same goal-directed protocol guided by stroke volume monitoring. No gelatin solution will be administered in this group. The total volume of crystalloid infusion is not limited.

Primary Outcome Measures

Name	Time	Method
Primary Outcome 1: Net fluid balance within 24 hours after surgery	Intraoperative period and postoperative 24 hours	Net fluid balance is defined as the difference between total infused volume and total output volume during surgery and the first 24 postoperative hours.; Input volume includes all study fluids (balanced gelatin solution or acetate Ringer's), albumin, blood products, and maintenance crystalloid infusion. Excluded are solvent volumes \<50 mL and non-therapeutic fluids such as irrigation or enteral/oral intake. Albumin is recorded in mL of solution administered. Blood product volumes are standardized: packed red blood cells 1 unit = 200 mL; plasma = actual volume; apheresis platelets 1 therapeutic dose = 250 mL; cryoprecipitate 1 unit = 25 mL (with center-specific adjustment allowed).; Output volume includes intraoperative blood loss, urine output, and measurable drainage (thoracic, abdominal, nasogastric, etc.), excluding insensible or unmeasurable losses.
Primary Outcome 2: Proportion of patients achieving hemodynamic stability within 24 hours after surgery	Postoperative 24 hours	Hemodynamic stability (HDS) is defined as meeting all of the following three criteria at postoperative 24 hours: 1. Mean arterial pressure (MAP) ≥65 mmHg without vasopressor support, sustained ≥1 hour after discontinuation of vasopressors, with all subsequent MAP measurements ≥65 mmHg.; 2. Blood lactate ≤2 mmol/L, based on the most recent venous or arterial sample.; 3. Urine output ≥1 mL/kg/h, based on the average over the preceding 6 hours. The outcome measure is the percentage of patients in each group who fulfill all three criteria.

Secondary Outcome Measures

Name	Time	Method
Secondary Outcome 9.1: All-cause mortality within 28 days after surgery	Postoperative day 1 to day 28	Death from any cause within 28 days postoperatively.
Secondary Outcome 9.2: All-cause mortality within 90 days after surgery	Postoperative day 1 to day 90	Death from any cause within 90 days postoperatively.
Secondary Outcome 1.1: Intensity of study drug use within 24 hours after surgery	Randomization to postoperative 24 hours	Cumulative volume of study drug administered from randomization to 24 hours postoperatively, standardized by ideal body weight (mL/kg).
Secondary Outcome 1.2: Blood product utilization rate within 24 hours after surgery	Randomization to postoperative 24 hours	Proportion of patients receiving any blood product during the intervention period, regardless of type. Each patient is counted once even if multiple blood products are used.
Secondary Outcome 1.3: Vasopressor load within 24 hours after surgery	Randomization to postoperative 24 hours	Vasopressor dose converted to norepinephrine-equivalent according to predefined equivalence table (norepinephrine:epinephrine:dopamine:phenylephrine:vasopressin = 1:1:0.01:0.01:0.02), normalized by ideal body weight and infusion time (μg/kg/min).
Secondary Outcome 1.4: Proportion of patients receiving inotropic drugs within 24 hours after surgery	Randomization to postoperative 24 hours	Proportion of patients treated with any inotrope (dobutamine, milrinone, levosimendan, etc.) within 24 hours postoperatively.
Secondary Outcome 2.1: Intraoperative lactate reduction magnitude	Baseline to end of surgery	Difference between baseline lactate and lactate at end of surgery (mmol/L).
Secondary Outcome 2.2: 24-hour lactate reduction magnitude	Baseline to postoperative 24 hours	Difference between baseline lactate and lactate at 24 hours after surgery (mmol/L).
Secondary Outcome 2.3: Normalization rate of capillary refill time (CRT) at end of surgery	From baseline to end of surgery	Proportion of patients with CRT ≤3 seconds at end of surgery, measured every 30 minutes from preoperative period to end of surgery using standardized glass-slide method.
Secondary Outcome 3.1: Proportion of patients with decrease in SOFA score at postoperative day 3 compared with baseline	Baseline to postoperative day 3	A decrease in SOFA total score compared with baseline is considered improvement. For sedated/intubated patients, the CNS score is excluded and the remaining 5-organ scores are compared.
Secondary Outcome 3.2: Proportion of patients with severe organ dysfunction within 3 days after surgery	Postoperative day 1 to day 3	Severe organ dysfunction is defined as SOFA score ≥3 in any organ system (respiratory, coagulation, liver, cardiovascular, renal, CNS) at least once during POD1-3. Deaths are counted as maximum scores.
Secondary Outcome 4.1: Incidence of acute kidney injury within 3 days after surgery	Baseline to postoperative day 3	Acute kidney injury (AKI) is defined according to KDIGO 2012 criteria, assessed at POD1, POD2, and POD3.
Secondary Outcome 4.2: Cumulative duration of renal replacement therapy within 28 days after surgery	Postoperative day 1 to day 28	Total number of days on renal replacement therapy (CRRT, intermittent hemodialysis, or peritoneal dialysis) during the 28 days after surgery.
Secondary Outcome 5: Incidence of coagulopathy within 3 days after surgery	Baseline to postoperative day 3	Coagulopathy is defined as PT prolongation \>3 seconds from baseline or INR \>1.5 at any time during POD1-3.
Secondary Outcome 6.1: Duration of ventilator-free time within 24 hours after surgery	Postoperative 24 hours	Total hours without invasive or non-invasive mechanical ventilation in the first 24 hours postoperatively. Interruptions \<1 hour are excluded.
Secondary Outcome 6.2: Duration of ventilator-free time within 7 days after surgery	Postoperative day 1 to day 7	Total days without invasive or non-invasive mechanical ventilation during the first 7 postoperative days. Interruptions \<1 day are excluded.
Secondary Outcome 7.1: Duration of vasopressor-free time within 24 hours after surgery	Postoperative 24 hours	Total hours during which MAP ≥65 mmHg is maintained without vasopressor support, sustained ≥1 hour, within the first 24 hours.
Secondary Outcome 7.2: Duration of vasopressor-free time within 72 hours after surgery	Postoperative day 1 to day 3	Total hours during which MAP ≥65 mmHg is maintained without vasopressor support, sustained ≥1 hour, within the first 72 hours.
Secondary Outcome 8.1: Length of ICU stay	From ICU admission to ICU discharge	Number of calendar days spent in the intensive care unit after surgery.
Secondary Outcome 8.2: Length of total hospital stay	From hospital admission to discharge	Number of calendar days from hospital admission to hospital discharge.

Trial Locations

Locations (9)

The First Affiliated Hospital, Sun Yat-sen University; 🇨🇳 Guangzhou, Guangdong, China

Zhongda Hospital, Southeast University; 🇨🇳 Nanjing, Jiangsu, China

The First Affiliated Hospital of Soochow University; 🇨🇳 Suzhou, Jiangsu, China

Affiliated Hospital of Xuzhou Medical University; 🇨🇳 Xuzhou, Jiangsu, China

Shandong Provincial Hospital; 🇨🇳 Jinan, Shandong, China

Zhongshan Hospital, Fudan University; 🇨🇳 Shanghai, Shanghai Municipality, China

The First Affiliated Hospital of Naval Military Medical University; 🇨🇳 Shanghai, Shanghai Municipality, China

Tianjin Medical University General Hospital; 🇨🇳 Tianjing, Tianjing, China

The Second Affiliated Hospital, Zhejiang University School of Medicine; 🇨🇳 Hangzhou, Zhejiang, China