Clinical Trials Logo

Clinical Trial Summary

The purpose of this study protocol is to determine if administering Intravenous Immunoglobulin (IVIG) for treatment of cardiopulmonary bypass (CPB) induced hypogammaglobulinemia in the early post-operative period can impact post-surgical outcomes (i.e., infection, fluid overload, and associated morbidities).


Clinical Trial Description

The intense post-CPB systemic inflammatory response syndrome (SIRS) is well described in neonates and infants. Increased production and release of pro-inflammatory cytokines, including Tumor Necrosis Factor, Interleukin1-B, and Interleukin-6 may suppress myocardial contractility, induce capillary leak, and activate complement and the clotting cascade - together leading to potential organ injury and death. SIRS is also frequently accompanied by impairment of the humoral immune response. One potential reason for this acquired immunodeficiency after cardiac surgery is the removal of immunoglobulins (Ig)s from the vascular space into other compartments where they are either sequestered or lost from the body altogether. We recently demonstrated that such Ig depletion from the intravascular compartment occurs in neonates following cardiac surgery. In a retrospective study of 53 children <3 months of age, we showed that plasma Immunoglobulin G (IgG) concentration drops precipitously after cardiac surgery and does not return to preoperative levels by 7 days; 51% of patients had hypogammaglobulinemia.

An important question is whether post-CPB low IgG has clinical consequence. IgG plays an essential role in the humoral immune system, activating complement and inducing the phagocytic system to neutralize pathogens. IgG deficiency is a known risk factor for infections in other pediatric populations. We were the first to demonstrate that post-CPB hypogammaglobulinemia is associated with worse clinical outcomes, including increased secondary infections (37% vs.12% in those without low IgG, p<0.05). These novel findings are paramount in that they identify a potential modifiable risk factor to improve outcomes after pediatric cardiac surgery with CPB. Additionally, low IgG is accompanied by fluid overload and prolonged mechanical ventilation. Igs constitute an important component of plasma oncotic pressure, so hypogammaglobulinemia may exacerbate anasarca, prolonging postoperative convalescence and increasing the morbidities associated with increased ICU length of stay.9

Igs have an increasingly recognized role in modulating the innate immune response. Present use of IVIG exceeds mere antibody replacement and extends to the treatment of autoimmune and inflammatory conditions. In fact, more than 75% of IVIG use in the U.S. today is for the treatment of inflammatory conditions, where proposed mechanisms include reduction of pro-inflammatory cytokine and adhesion molecule expression, superantigen neutralization, restoration of glucocorticoid responsiveness, and blockade of complement fragment deposition. It is plausible that IVIG could benefit neonates after cardiac surgery not only via restoration of humoral opsonization capacity, but also as a modulator of innate immunity and SIRS. According to this model, tissue injury, CPB, and shock trigger SIRS, leading to hypogammaglobulinemia and resultant increased susceptibility to inflammatory dysregulation which might be ameliorated via administration of IVIG.

In an adult study, IVIG failed to benefit postoperative cardiac patients with severe SIRS. However, the dose of IVIG given was relatively small compared with that typically given for autoimmune and inflammatory conditions. Neonates and infants may be more susceptible to the harmful effects of acquired hypogammaglobulinemia than adults as they may be unable to generate adequate quantities of antibodies in response to pathogens, relying mainly on maternal Igs until around the 4th to 6th month of life. In addition, they display an exaggerated inflammatory response to CPB as compared with older children and adults, so they might stand to benefit more from IVIG as an immunomodulator.

Because of the increased vulnerability to acquired infection and other morbidities in the setting of hypogammaglobulinemia as result of enhanced SIRS and immune dysfunction, it is feasible that normalization of IgG concentration in the neonatal and infant population may improve clinical outcomes via restoration of the humoral immune system, modulation of the innate immune system, and restoration of intravascular oncotic pressure. The appropriate IgG level threshold for treatment and optimal plasma IgG level to target after administration of IVIG are presently unknown. ;


Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment


Related Conditions & MeSH terms


NCT number NCT02043379
Study type Interventional
Source University of Alabama at Birmingham
Contact
Status Completed
Phase N/A
Start date May 2014
Completion date June 2015

See also
  Status Clinical Trial Phase
Recruiting NCT05654272 - Development of CIRC Technologies
Recruiting NCT04992793 - Paediatric Brain Injury Following Cardiac Interventions
Recruiting NCT05213598 - Fontan Associated Liver Disease and the Evaluation of Biomarkers for Disease Severity Assessment
Completed NCT04136379 - Comparison of Home and Standard Clinic Monitoring of INR in Patients With CHD
Completed NCT04814888 - 3D Airway Model for Pediatric Patients
Recruiting NCT04920643 - High-exchange ULTrafiltration to Enhance Recovery After Pediatric Cardiac Surgery N/A
Completed NCT05934578 - Lymphatic Function in Patients With Fontan Circulation: Effect of Physical Training N/A
Recruiting NCT06041685 - Effect of Local Warming for Arterial Catheterization in Pediatric Anesthesia N/A
Recruiting NCT05902013 - Video Laryngoscopy Versus Direct Laryngoscopy for Nasotracheal Intubation N/A
Not yet recruiting NCT05687292 - Application of a Clinical Decision Support System to Reduce Mechanical Ventilation Duration After Cardiac Surgery
Not yet recruiting NCT05524324 - Cardiac Resynchronization Therapy in Adult Congenital Heart Disease With Systemic Right Ventricle: RIGHT-CRT N/A
Completed NCT02746029 - Cardiac Murmurs in Children: Predictive Value of Cardiac Markers
Completed NCT03119090 - Fontan Imaging Biomarkers (FIB) Study
Completed NCT02537392 - Multi-micronutrient Supplementation During Peri-conception and Congenital Heart Disease N/A
Recruiting NCT02258724 - Swiss National Registry of Grown up Congenital Heart Disease Patients
Terminated NCT02046135 - Sodium Bicarbonate to Prevent Acute Kidney Injury in Children Undergoing Cardiac Surgery Phase 2
Completed NCT01966237 - Milrinone Pharmacokinetics and Acute Kidney Injury
Recruiting NCT01184404 - Bosentan Improves Clinical Outcome of Adults With Congenital Heart Disease or Mitral Valve Lesions Who Undergo CArdiac Surgery N/A
Completed NCT01548950 - Drug Therapy and Surgery in Congenital Heart Disease With Pulmonary Hypertension N/A
Completed NCT01178710 - Effect of Simvastatin on Cardiac Function N/A