Gelaspan vs Crystalloid Therapy in Sepsis (SPACES)

Fudan University

Status and phase: Begins enrollment in 1 month; Phase 4

Conditions: Intra-Abdominal Infections; Sepsis

Treatments: Drug: Acetate Ringer's Solution; Drug: Balanced Gelatin Solution

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT07172451

Ethics Approval No. B2025-465R (Other Identifier)

ZSANES.B2025-465R

Details and patient eligibility

About

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.

Full 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.

Enrollment: 318 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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318 participants in 2 patient groups

Balanced Gelatin Solution

Experimental group

Description:

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.

Treatment:

Drug: Balanced Gelatin Solution

Crystalloid Solution

Active Comparator group

Description:

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.

Treatment:

Drug: Acetate Ringer's Solution