Randomized Control Study in REsuscitation of SEpsis Trial

Protocol Title: Randomized Clinical Trial Comparing Crystalloids vs. Synthetic Plasma for Fluid Resuscitation in Children with Sepsis - REsuscitation of Sepsis Trial (RESET): Feasibility and Comparative Study

Development Phase: Phase IV Study

Sponsor:

Fundación Cardioinfantil - Instituto de Cardiología Children's Hospital of Pittsburgh - Center for Trauma and Transfusion Medicine Research, University of Pittsburgh, Pittsburgh, USA

Medical Sponsor and International Coordinator Dr. Jaime Fernández - Pediatric Intensivist, Head of the Pediatric Intensive Care Unit, Fundación Cardioinfantil, Bogotá, Colombia Dr. Phillip Spinella, MD, FCCM - Pediatric Intensivist, Department of Surgery and Anesthesia, Children's Hospital of Pittsburgh; Emeritus Professor, Department of Surgery and Critical Care, University of Pittsburgh; Director, Center for Trauma and Transfusion Medicine Research, University of Pittsburgh, Pittsburgh, USA

Drug Manufacturer: Octapharma

Study Center: Fundación Cardioinfantil - Bogotá, Colombia

Study Objectives

Primary Objective:

To evaluate the feasibility in terms of efficacy and safety of crystalloids versus synthetic fresh plasma as the initial resuscitation fluid in children presenting with septic shock. Feasibility study.

Secondary Objectives:

• Compare hemodynamic parameters using continuous non-invasive cardiac output monitoring (iCON®) between groups.
• Assess intravascular volume via echocardiography at 6 ± 2, 24 ± 8, and 48 ± 8 hours across groups.
• Compare the total volume of normal saline, lactate, or plasma administered for resuscitation within the first 6, 24, and 48 hours.
• Evaluate net fluid balance at 24 and 48 hours.
• Compare oxygenation parameters (S/F ratio, P/F ratio, oxygenation index) between the two groups at 0, 6, 24, and 48 hours in ventilated children.
• Assess organ dysfunction scores (PELOD, pSOFA, and NP-MODS) daily for 48 hours.
• Compare peak inotropic scores daily over 48 hours.
• Evaluate endothelial injury markers and hemostatic parameters.
• Assess inflammatory markers and coagulation activation measures.
• Monitor transfusion-related reactions.
• Compare healthcare-associated infections.
• Assess 28-day mortality and cause of death.

Study Design A prospective, randomized, open-label, feasibility-controlled trial.

Investigational Medicinal Product

Patients diagnosed with septic shock who meet the inclusion criteria will be randomly assigned to one of three intervention arms:

• Group A: Bolus dose of 10 mL/kg normal saline (NS) (max. 500 mL) administered over <15 minutes.
• Group B: Bolus dose of 10 mL/kg Ringer's lactate (max. 500 mL) administered over <15 minutes.
• Group C: Pharmaceutical fresh frozen plasma (OCTAPLAS LG®), bolus dose of 10 mL/kg (max. 500 mL) administered over <15 minutes.

The commercial product OCTAPLAS LG® has been registered with INVIMA in Colombia for five years and is used as a plasma replacement in cardiac surgery, hematologic diseases, or intensive care settings where blood bank plasma is unavailable.

Study Population Children aged 1 month to 18 years diagnosed with sepsis, admitted to the Pediatric Intensive Care Unit (PICU) at Fundación Cardioinfantil over a 12-month period, and meeting eligibility criteria.

Inclusion criteria

• Age: ≥1 month (corrected gestational age) to 18 years.
• Diagnosis of sepsis with at least one of the following conditions:
• Signs of poor perfusion: prolonged capillary refill ≥2 sec, weak peripheral pulses, unexplained metabolic acidosis (base deficit > (-)5.0 mEq/L), altered. mental status, lactate ≥2 mmol/L (sample drawn without tourniquet use. (Appendix 2). OR
• Systolic blood pressure (SBP) below the 5th percentile for age.
• Signed informed consent from the patient's legal guardian.

Exclusion criteria

• Receipt of ≥2 boluses of NS 0.9% or balanced solution in the last 24 hours for the current sepsis episode (bolus defined as ≥10 mL/kg (max. 500 mL) of NS/RL given in <30 min).
• Known allergic reaction to plasma-derived products.
• Known IgA deficiency.
• Suspected or confirmed congestive heart failure.
• Nephrotic syndrome.
• Known chronic kidney disease with fluid overload or congestive heart failure.
• Diagnosed hemorrhagic dengue fever confirmed by antigen or serology (NS1 or IgM positive).