Randomized Control Study in REsuscitation of SEpsis Trial

NCT07035509 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: CEIC-456-2024
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

Crystalloids vs. Synthetic Plasma for Fluid Resuscitation in Children with Sepsis - REsuscitation of SEpsis Trial (RESET): A Comparative and Feasibility Study This research study, called the REsuscitation of SEpsis Trial (RESET), is a randomized clinical trial comparing crystalloids and synthetic plasma for fluid resuscitation in children with sepsis. Below, we explain some key aspects you should be aware of. What is a Clinical Trial? A clinical trial is a type of medical research designed to gather more information on how our bodies respond to medications or other treatments. Most new medical treatments must be evaluated in clinical trials before they can be approved by government agencies. These agencies ensure that new treatments are not only safe but also beneficial for patients-what medicine refers to as being "safe and effective." If a new treatment has not yet been approved, it is considered "experimental." Researchers analyze the results of multiple clinical trials to determine which medications work best and how they function. The advancement of medical science requires the participation of many people in numerous studies worldwide. What is the Purpose of This Study? This study evaluates whether Octaplas LG helps children and adolescents with sepsis and whether it improves the function of blood vessels inflamed due to infection. Sepsis occurs when an infection severely affects a person's health. Octaplas LG is a medication approved for use in Colombia. It is known as pharmaceutical plasma and is obtained from voluntary donors worldwide. It undergoes an ultra-detailed sterilization process using the most advanced techniques for processing blood derivatives. In medicine, fresh frozen plasma (FFP) is typically used, which is the equivalent of Octaplas LG but with far fewer industrial sterilization processes. These additional processes in Octaplas LG significantly reduce the risk of transmitting infections. Although Octaplas LG is approved by INVIMA, its use for fluid resuscitation has not yet been approved. This study will compare Octaplas LG with normal saline solution and Ringer's lactate, which are commonly used for rehydrating patients. All three treatments will be administered in the same manner. Why is My Child Being Asked to Participate? Your child is being invited to participate in this clinical study because: They are receiving care in the pediatric intensive care unit (PICU). They are between one month and 18 years old. They have been diagnosed with sepsis and require fluid resuscitation. Your child's participation is voluntary. If you decide not to participate, your child will not lose any medical benefits. Your child's doctor has determined that they may be a good candidate for this study. You are free to discuss participation with your family, friends, or another physician. Some members of your child's healthcare team may also be involved in this research. They are dedicated to your child's care as well as the objectives of this study. However, you are not obligated to participate. If you choose to enroll your child, you will be asked to sign an informed consent form. How Will My Child Be Assigned to a Treatment Group? Upon admission to the pediatric intensive care unit (PICU), if your child has a confirmed sepsis diagnosis and requires intravenous fluids or plasma to support heart function, they will be randomly assigned to one of the three treatment groups. Randomization is a research method used in clinical trials to assign patients to study groups in an unbiased way-similar to drawing numbers from a hat. Neither you, your child's doctor, nor the researchers will choose which group your child is placed in. Instead, a computer will randomly assign them to a group. Treatment Groups: Group 1: Normal Saline (0.9% Sodium Chloride) Your child will receive the standard treatment for sepsis, including antibiotics, intravenous fluids, heart function monitoring, mechanical ventilation if needed, and blood pressure medications (vasopressors) if necessary. Group 2: Ringer's Lactate In addition to standard sepsis management, your child will receive Ringer's lactate, another commonly used resuscitation fluid in pediatric sepsis. Group 3: Octaplas LG In addition to standard sepsis management, your child will receive pharmaceutical synthetic plasma, which contains proteins and essential blood components that have undergone advanced processing to eliminate the risk of infectious disease transmission. How Many Children Will Participate in This Study? At Fundación Cardioinfantil-Instituto de Cardiología, we are seeking the participation of approximately 150 children in this study. How Long Will My Child Be in the Study? Your child will remain in their assigned treatment group for up to 28 days from PICU admission or until they no longer require intensive care hospitalization.

Conditions

Septic Shock; Pediatric Critical Illness

Keywords

sepsis; Septic shock; Fluid bolus; plasma; pediatric; crystalloids

Outcome Measures

Primary Outcomes (14)

• Feasibility in terms of efficacy and safety of crystalloids versus synthetic fresh plasma as the initial resuscitation fluid in children presenting with septic shock: Rate of Signed Informed Consent

  Proportion of patients for whom signed informed consent is obtained prior to the intervention.

  Within the first 2 hours after presentation to the PICU. Percentage (%)

• Feasibility in terms of efficacy and safety of crystalloids versus synthetic fresh plasma as the initial resuscitation fluid in children presenting with septic shock: Time to Plasma Administration

  Time elapsed from clinical indication to administration of the assigned plasma product.

  Within the first 24 hours after admission. Minutes (min)

• Feasibility in terms of efficacy and safety of crystalloids versus synthetic fresh plasma as the initial resuscitation fluid in children presenting with septic shock: Follow-up Rate

  Proportion of patients with complete follow-up until PICU discharge or day 28, whichever comes first.

  From PICU admission until day 28 or PICU discharge. Percentage (%)

• Feasibility in terms of efficacy and safety of crystalloids versus synthetic fresh plasma as the initial resuscitation fluid in children presenting with septic shock: Ability to Obtain and Process Biological Samples

  Percentage of biological samples (for clinical laboratory tests, inflammatory markers, and endothelial biomarkers) successfully collected and processed according to protocol.

  During the first 24 hours post-intervention. Percentage (%)

• Feasibility in terms of efficacy and safety of crystalloids versus synthetic fresh plasma as the initial resuscitation fluid in children presenting with septic shock: Incidence of Clinical Outcomes

  Incidence of clinical outcomes such as mechanical ventilation, inotropic support, multiple organ dysfunction, or mortality.

  Up to 28 days post-intervention or until PICU discharge. Number of events (n), Percentage (%)

• Efficacy of crystalloids versus synthetic fresh plasma as the initial resuscitation fluid in children presenting with septic shock in clinical variables and supports: Oxygenation as Assessed by PaO₂/FiO₂ Ratio

  Evaluation of oxygenation using the PaO₂/FiO₂ ratio.

  Within the first 24 hours of intervention. Ratio (unitless)

• Efficacy of crystalloids versus synthetic fresh plasma as the initial resuscitation fluid in children presenting with septic shock in clinical variables and supports: Oxygenation Index (OI)

  Oxygenation Index calculated as (FiO₂ × MAP / PaO₂) × 100.

  Within the first 24 hours of intervention. Unitless value

• Efficacy of crystalloids versus synthetic fresh plasma as the initial resuscitation fluid in children presenting with septic shock in clinical variables and supports: Intravascular Volume Status

  Assessment of intravascular volume status based on clinical and hemodynamic parameters.

  Within the first 24 hours of intervention. Categorized as improved / no change / worsened (qualitative)

• Efficacy of crystalloids versus synthetic fresh plasma as the initial resuscitation fluid in children presenting with septic shock in clinical variables and supports: Inotropic Score

  Quantification of cardiovascular support based on standard inotropic scoring systems.

  Maximum value during the first 24 hours post-intervention. Inotropic score (numeric)

• Efficacy of crystalloids versus synthetic fresh plasma as the initial resuscitation fluid in children presenting with septic shock in clinical variables and supports: Endothelial Injury Markers

  Measurement of circulating endothelial biomarkers such as syndecan-1, angiopoietin-2, or others defined in protocol.

  Baseline and within 24 hours post-intervention. ng/mL

• Efficacy of crystalloids versus synthetic fresh plasma as the initial resuscitation fluid in children presenting with septic shock in clinical variables and supports: Hemostatic Measures

  Evaluation of coagulation parameters including PT, aPTT, fibrinogen, and D-dimer levels.

  Baseline and within 24 hours post-intervention. Seconds (for PT/aPTT), mg/dL or ng/mL (as applicable)

• Efficacy of crystalloids versus synthetic fresh plasma as the initial resuscitation fluid in children presenting with septic shock in clinical variables and supports: Incidence of New or Progressive Organ Failure

  Number of patients with new or worsening organ dysfunction during hospitalization.

  Up to 28 days post-intervention or until PICU discharge. Number of patients (n), Percentage (%)

• Efficacy of crystalloids versus synthetic fresh plasma as the initial resuscitation fluid in children presenting with septic shock in clinical variables and supports: 28-Day All-Cause Mortality

  Death from any cause within 28 days of randomization.

  Up to day 28. Number of deaths (n), Percentage (%)

• Efficacy of crystalloids versus synthetic fresh plasma as the initial resuscitation fluid in children presenting with septic shock in clinical variables and supports: Cause of Death

  Categorization of causes of death (e.g., refractory shock, respiratory failure, neurologic injury).

  Up to 28 days post-randomization. Categorical (by cause)

Secondary Outcomes (19)

• Compare hemodynamic parameters using continuous non-invasive cardiac output monitoring (iCON®) between groups: Systemic Vascular Resistance (SVR)

  During the 24-hour intervention period. dyn·s/cm⁵

• Compare hemodynamic parameters using continuous non-invasive cardiac output monitoring (iCON®) between groups: Cardiac Output (CO)

  During the 24-hour intervention period. Liters per minute (L/min)

• Compare hemodynamic parameters using continuous non-invasive cardiac output monitoring (iCON®) between groups: Cardiac Index (CI)

  During the 24-hour intervention period. Liters per minute per square meter (L/min/m²)

• Compare hemodynamic parameters using continuous non-invasive cardiac output monitoring (iCON®) between groups: Stroke Volume Variability (SVV)

  During the 24-hour intervention period. Percentage (%)

• Compare hemodynamic parameters using continuous non-invasive cardiac output monitoring (iCON®) between groups: Pulse Pressure Variation (PPV)

  During the 24-hour intervention period. Percentage (%)

Study Arms (3)

OCTAPLAS LG

EXPERIMENTAL

Pharmaceutical fresh frozen plasma (OCTAPLAS LG®), bolus dose of 10 mL/kg (max. 500 mL) administered over \<15 minutes

Biological: Pharmaceutical fresh frozen plasma

Normal saline

ACTIVE COMPARATOR

Bolus dose of 10 mL/kg normal saline (NS) (max. 500 mL) administered over \<15 minutes.

Drug: Normal Saline

Ringer Lactate

ACTIVE COMPARATOR

Bolus dose of 10 mL/kg Ringer's lactate (max. 500 mL) administered over \<15 minutes.

Drug: Ringer lactate (RL)

Interventions

Pharmaceutical fresh frozen plasma BIOLOGICAL

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

OCTAPLAS LG

Normal Saline DRUG

Bolus dose of 10 mL/kg normal saline (NS) (max. 500 mL) administered over \<15 minutes.

Normal saline

Ringer lactate (RL) DRUG

Bolus dose of 10 mL/kg Ringer's lactate (max. 500 mL) administered over \<15 minutes.

Ringer Lactate

Eligibility Criteria

• Age: 4 Weeks - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Fundación Cardioinfantil Instituto de Cardiología: lead
• University of Pittsburgh: collaborator

Study Sites (1)

Fundacion CardioInfantil - Instituto de Cardiología

Bogotá, Bogota D.C., 111031, Colombia

Location

Related Publications (3)

• Iba T, Maier CL, Helms J, Ferrer R, Thachil J, Levy JH. Managing sepsis and septic shock in an endothelial glycocalyx-friendly way: from the viewpoint of surviving sepsis campaign guidelines. Ann Intensive Care. 2024 Apr 24;14(1):64. doi: 10.1186/s13613-024-01301-6.

  PMID: 38658435 BACKGROUND

• Obonyo NG, Sela DP, Raman S, Rachakonda R, Schneider B, Hoe LES, Fanning JP, Bassi GL, Maitland K, Suen JY, Fraser JF. Resuscitation-associated endotheliopathy (RAsE): a conceptual framework based on a systematic review and meta-analysis. Syst Rev. 2023 Nov 22;12(1):221. doi: 10.1186/s13643-023-02385-0.

  PMID: 37990333 BACKGROUND

• Torres LN, Chung KK, Salgado CL, Dubick MA, Torres Filho IP. Low-volume resuscitation with normal saline is associated with microvascular endothelial dysfunction after hemorrhage in rats, compared to colloids and balanced crystalloids. Crit Care. 2017 Jun 29;21(1):160. doi: 10.1186/s13054-017-1745-7.

  PMID: 28659186 BACKGROUND

MeSH Terms

Conditions

Shock, Septic; Sepsis

Interventions

Saline Solution; Ringer's Lactate

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Philp Spinella Dr, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jaime Fernandez Dr, PHD

CONTACT

+576016672727; jfernandez@lacardio.org

Lorena Acevedo Dr, MsC

CONTACT

+57601672727; gacevedo@lacardio.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients diagnosed with septic shock who meet the inclusion criteria will be randomly assigned to one of three intervention arms: * Group 1: Bolus dose of 10 mL/kg normal saline (NS) (max. 500 mL) administered over \<15 minutes. * Group 2: Bolus dose of 10 mL/kg Ringer's lactate (max. 500 mL) administered over \<15 minutes. * Group 3: Pharmaceutical fresh frozen plasma (OCTAPLAS LG®), bolus dose of 10 mL/kg (max. 500 mL) administered over \<15 minutes.

Study Record Dates

• First Submitted: March 4, 2025
• First Posted: June 25, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): July 15, 2026
• Study Completion (Estimated): July 15, 2026
• Last Updated: June 25, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CO (1)