Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05401695 |
| Other study ID # |
Ped Critical Care KCMH |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
July 1, 2021 |
| Est. completion date |
April 30, 2022 |
Study information
| Verified date |
May 2022 |
| Source |
Chulalongkorn University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Sepsis is a major healthcare problem and leading cause of death in the pediatric population.
Despite advances in supportive care of critically ill patients, sepsis remains an important
cause of death worldwide in children. Overall, sepsis incidence peaked in early childhood.
There were an estimated 20.3 million incident sepsis cases worldwide among children younger
than 5 years. The Surviving Sepsis Campaign (SSC), which standardized the evidence-base
approach to management of septic shock and other sepsis-associated organ dysfunction in
children, was recently updated. Nevertheless, mortality and costs are still high.
Sepsis is characterized by a complex systemic inflammatory response to a microbial pathogen.
A dysregulated host response to infection may result in life-threatening multi-organ
dysfunction. Endotoxin, which is found in the outer membrane of Gram-negative bacteria, plays
an important role in the pathogenesis of septic shock by producing proinflammatory cytokines.
High levels of endotoxin and proinflammatory cytokines are associated with a high mortality
rate.
Treatment strategies in sepsis and septic shock include early and adequate fluid
resuscitation, vasopressors and inotropic support when indicated, early use of broad-spectrum
antibiotics with source control, with close monitoring and organ support, if indicated. Other
therapies such as immune-modulation and blood purification have been tried to improve
outcomes in patients with sepsis and septic shock. Immunomodulation and blood purification
techniques aim at restoring the balance of the immune response to infection, by removing the
triggers for the response and the cytokines produced and thereby achieve immune homeostasis.
Removing endotoxin and inflammatory cytokines would be an effective adjunctive approach in
the management of severe sepsis.
Direct hemoadsorption (HA) is an extracorporeal technique utilized for blood purification. It
involves the passage of blood through an adsorption cartridge, where solutes are removed by
direct binding to the sorbent material. Over the years, new adsorption cartridge, with
improved characteristics have been developed. Resin-directed hemoadsorption is associated
with improved oxygenation, hemodynamic status and cardiac function. However, most studies
include only adults, and little information is available regarding the clinical experience
and efficacy of blood purification for pediatric septic shock.
This pilot study aimed to evaluate the overall clinical outcomes among children who received
direct hemoadsorption as an adjunctive treatment for refractory septic shock with high
severity scores, compared with outcomes among children admitted to the PICU who received
standard treatment.
Description:
Study design This pilot study is the prospective interventional cohort study with comparison
to a historical control group at a nine-bed PICU at a university referral hospital. Children
with septic shock who meet the inclusion criteria will be enrolled. The HA-treated group will
be enrolled between July 2021 and May 2022. The historical control group was composed of
patients treated between May 2019 and May 2021. Baseline clinical severity scores were
matched between the two groups. Investigators will obtained informed consent from the
families of all patients. The confounding factor was controlled by matching ratio 1:3
(baseline clinical severity score matching). So sample size of intervention (HA) group was
calculate about 10 cases.
Patients The HA group included children with sepsis, as defined by the Surviving Sepsis
Campaign guideline 2020, who were admitted to our PICU during the study period. All children
initially received routine treatment for septic shock, including intravenous fluid
resuscitation, antibiotics, removal of source of infection and inotropic drugs within 6 hours
after the diagnosis of sepsis. Patients were included if they: 1) are 30 days to 15 years of
age, 2) require any dose of at least one vasopressor and 3) has a Pediatric Logistic Organ
Dysfunction (PELOD)-2 score ≥ 10 or Pediatric Risk of Mortality (PRISM)-3 score ≥ 15.
Patients receiving end-of-life support, those with uncontrolled bleeding were excluded. The
historical control group included patients with sepsis who were admitted to our PICU with the
same inclusion criteria and received standard treatment. Patients will be matched according
to baseline clinical severity score.
Hemoadsorption (HA) treatment An HA330 disposable hemoperfusion cartridge (HA330; Jafron,
Zhuhai City, China) was used with a continuous renal replacement therapy (CRRT) machine
(Aquarius® or Primaflex®) in the intervention group. Investigators will select a blood
circuit for each machine according to the patient's body weight. For the Aquarius machine,
Aqualine S (64-mL blood volume) will be used for body weight < 30 kg and Aqualine (105-mL
blood volume) will be used for weight ≥ 30 kg. Four types of blood circuit will be utilized
with the Prismaflex machine, including Prismaflex HF20 set (60 mL) for weight < 3-11 kg,
Prismaflex M60 set (93 mL) for weight 11-30 kg and Prismaflex M100 set (152 mL) for weight >
30 kg. After rinsing with normal saline solution with heparin, priming the blood circuit and
the cartridge with normal saline solution; using 5% albumin or packed red cells (PRC) when
the volume of the extracorporeal circuit is more than 10% of the circulatory volume of the
patient. If the albumin level is below 3.5 g/dL and hematocrit is above 30%, 5% albumin will
be used for priming. If hematocrit is below 30%, PRC will be used. Vascular access will be
established with ultrasound-guided insertion of a double-lumen venous catheter into the right
internal jugular or femoral vein. The size of the double-lumen catheter is 8 French (Fr) for
patients weighing 6-15 kg, 9-10 Fr for those weighing 15-30 kg and 11.5 Fr for those weighing
> 30 kg. HA will be performed for a maximum of 4 hours, and the second session will be
started approximately 24 hours after the end of the first session. The blood flow rate will
be started low and be gradually increased while monitoring real-time blood pressure and vital
signs with an arterial-line monitor. After the end of the HA session, CRRT will be continued
if required.
Data collection and study endpoints Demographic data, underlying disease and source of
infection are extracted from patients' hospital charts. Blood gas data, type of respiratory
support, dose of vasopressors and laboratory data will be recorded at baseline, 24 hours, 48
hours and 72 hours. The baseline is define as a time before HA treatment in the intervention
group and when patients will be noted to have no response to initial resuscitation in the
control group. The severity of organ dysfunction or failure will be expressed with the
PELOD-2 score and PRISM-3 score and recorded at the four time points above. The dose of
vasoactive/vasopressor agents will be expressed as the vasoactive inotropic score (VIS),
calculated as: dopamine dose + dobutamine dose + (epinephrine dose × 100) + (norepinephrine
dose × 100) + (milrinone dose × 10) + (vasopressin dose × 10,000), with doses expressed as
mcg/kg/min for most drugs and as U/kg/min for vasopressin. The primary endpoints are the
reduction in PELOD-2 and PRISM-3 scores at 72 hours, with adjustment for baseline between the
HA and control groups. The secondary endpoints are the reductions in IL-6, VIS, oxygenation
index, serum creatinine, base excess and lactate at 72 hours; length of PICU stay, hospital
stay and mechanical ventilation; and 28-day mortality.
Laboratory methods Serum samples are analyzed by Direct Ion Selective Electrode for arterial
blood gas analysis, which include the data of arterial lactate, base excess and oxygenation
index. Complete blood count (CBC) are analyzed by Chemical dye, Laser scattering, SF Cube,
Sheath Fluid and Impedance Method to evaluated white blood cell count (WBC) and platelets.
Serum creatinine (Cr) and other blood chemistry are analyzed by Reflotron method. IL-6 is
analyzed by Electrochemiluminescence immunoassay (ECLIA).
Data analysis and statistics Data analysis using the median with range (minimum-maximum) or
mean ± standard deviation. Investigators will use Student's t-test analysis for continuous
variables data and Fisher's exact test for categorical variables data. Within-group analysis
of PELOD-2, PRISM-3, oxygenation index, VIS, creatinine, base excess, endotoxin levels and
lactate will be performed with paired t-tests; between-group comparisons are performed with
analysis of covariance (ANCOVA) at 72 hours, with adjustment for the baseline in each group.
