Preventing Acute Kidney Injury (AKI) in Pediatric Patients

Acute Kidney Injury Clinical Trial

— AKI  

Official title:

The Effect of Aminophylline on Preventing Acute Kidney Injury in Pediatric Patients Undergoing Open Heart Surgery

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03897335
• Other study ID #: Acute Kidney Injury
• Status: Recruiting
• Phase: Phase 3
• Start date: February 7, 2019
• Est. completion date: February 1, 2024

Study information

• Verified date: April 2022
• Source: Le Bonheur Children's Hospital
• Contact: Lauren Davis
• Phone: 901-287-4594
• Email: lauren.davis2[@]lebonheur.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the effects of peri-operative administration of Aminophylline versus Saline placebo in the preservation of renal function and the attenuation of renal injury in pediatric patients undergoing open heart surgery.

Description:

Cardiac palliative/ correction surgeries in pediatric patients involve significant morbidity and mortality risks. Kidney function is frequently affected from cardiac surgery in these children. Studies identify the incidence of acute kidney injury (AKI) to be approximately 54% when defined by serum biomarkers (e.g. serum creatinine) and urine output criteria. The need for renal replacement therapy (RRT) for newborns and infants after cardiac surgery is reported as 2% to 17% in the literature. There are several reported risk factors for the development of AKI in this population. These are the complexities of the underlying heart disease and the surgical procedure, duration of cardiopulmonary bypass, functional single ventricle heart disease, circulatory arrest and low cardiac output syndrome in the post-operative period. AKI can cause worsening fluid overload compromising ventilation and lung function, predisposition to overwhelming infections and cytokine-mediated inflammatory state. The presence of AKI significantly increases the mortality that is associated with cardiac surgery in these very young patients, reported as high as 79% in the literature. There have been several reports suggesting that early intervention with AKI using renal replacement therapy (RRT) may improve patient mortality. Successful prevention strategies for AKI have not been reported for this high-risk population. Adenosine has been demonstrated to regulate renal circulation and metabolism. It is a breakdown product of adenosine triphosphate/adenosine diphosphate (ATP/ADP) metabolism and accumulates in AKI. At baseline, the barely detectable renal parenchymal adenosine levels can increase to 10-100 times following an ischemic insult. These are typical seven trans-membrane spanning domains with a coupled G-protein at the intracellular end. Adenosine receptors are located ubiquitously in many tissues. Adenosine acts as a vasodilator in all other tissues but the renal parenchyma. The interaction of AT-II with adenosine converts adenosine to a vasoconstrictor in renal microvasculature. Adenosine acts on the A1 receptors (A1 R) in the afferent arterioles, causing reduced glomerular blood flow and glomerular filtration rate (GFR), as well as stimulating renin release from the kidney parenchyma. Adenosine plays an important role in generating the vasoconstrictive response in the renal vasculature to hypoxia and ischemia. Early interventions by blocking the actions of adenosine on A1 R may restore glomerular blood flow and recover GFR. The study rationale is that Aminophylline and Theophylline are competitive non-selective inhibitors of adenosine. Therefore, even though aminophylline infusion (iv) has no effect on renal blood flow rate at baseline, it can ameliorate the decrease in renal blood flow rate following adenosine infusion. This property can improve renal function when the main mechanism of insult induces vasoconstriction. Both early and late administration of aminophylline protects renal function after ischemia-reperfusion injury in rats. Aminophylline has also been reported to successfully reverse newborn renal failure, prevent renal failure in perinatal asphyxia, and reverse acute kidney injury secondary to calcineurin induced nephropathy. Both theophylline and aminophylline have been used for prophylaxis of renal impairment during aorto-coronary bypass surgery in adults and the results have not been consistent for either a positive or negative effect. There have been no trials reported on the effect of aminophylline or theophylline to prevent or ameliorate acute kidney injury in children with congenital heart defects going through cardiac surgery. Additionally, we are examining the components of serotonin biosynthesis to determine if these levels can act as markers of acute kidney injury in pediatric patients undergoing open heart surgery.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: February 1, 2024
• Est. primary completion date: February 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

Inclusion Criteria:

Cohort 1

• All children undergoing open heart surgery for congenital heart defects with or without circulatory arrest
• Neonates (<28 days old) and infants (<1 years of age)
• Hypoplastic L heart syndrome or its variants.
• Coarctation with aortic arch hypoplasia.
• Interrupted aortic arch.
• TAPVR (Total anomalous pulmonary venous return)
• Patients with complex congenital heart defects

Cohort 2:

• Orthotopic heart transplantation patients.
• Patients = 18 years of age
• Congenital heart defects
• Cardiomyopathy (Dilated/Hypertrophic/Restrictive/Left Ventricular Non-compaction)

Exclusion Criteria:

• Children under the age of 12 months undergoing bypass for any condition that is not categorized as congenital heart defect
• History of seizures
• History of significant tachyarrhythmia.

Related Conditions & MeSH terms

• Acute Kidney Injury
• Wounds and Injuries

Intervention

Drug:
• Aminophylline
Aminophylline pre cardiopulmonary bypass and immediately post cardiopulmonary bypass. The dose will be Aminophylline 5 mg/kg/dose, max 350 mg slow infusion. The infusion rate duration will be standardized to 20 minutes. There will be no other aminophylline treatments for the first post-op five days.
• Placebo
The placebo group will not receive any aminophylline treatments for the first post-op five days

Locations

Country	Name	City	State
United States	LeBonheur Children's Hospital	Memphis	Tennessee
United States	LeBonheur Children's Hospital	Memphis	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Le Bonheur Children's Hospital

Country where clinical trial is conducted

United States, 

References & Publications (47)

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* Note: There are 47 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Concentration of Delta urinary neutrophil gelatinase-associated lipocalin (NGAL)	1 Delta urinary NGAL at 6 hours post cardiopulmonary (CPB) and Delta plasma NGAL at 2 hours post CPB.	at 2 hours post CPB.
Other	Time to extubation (hours)	Time to extubation (hours) number of hours post surgery	during hospitalization, up to 8 days
Other	Time to chest closure (hours)	Time to chest closure (hours) from start time of incision to chest closure during procedure	during hospitalization, up to 3 days
Other	Time to discharge from cardiovascular intensive care unit (CVICU) (days)	Time to discharge from CVICU (days)	during hospitalization, approximate 5 days
Other	Duration of hospital stay (Days).	Duration of hospital stay (Days).	during hospitalization, approximate 8 days
Other	Dialysis requirement (yes/no)	Dialysis requirement (yes/no)	during hospitalization, approximate 5 days
Other	Time to return to preoperative weight.	Time to return to preoperative weight.	during hospitalization, approximate 8 days
Other	Inotropic score	Inotropic score Calculation of Inotropic score (IS) and Vasoactive inotropic score (VIS). IS(a) = dopamine dose (lg/kg/min) ? dobutamine dose (lg/kg/min) ? 100 9 epinephrine dose (lg/kg/min) VIS(b) = IS ? 10 9 milrinone dose (lg/kg/ min) ? 10,000 9 vasopressin dose (U/kg/ min) ? 100 9 norepinephrine dose (lg/kg/min) IS inotrope score, VIS vasoactive-inotropic score	at 7 days post operative
Other	Peritoneal dialysis catheter output.	Peritoneal dialysis catheter output through study completion	during hospitalization, up to 8 days
Other	Transfusion requirements intraoperatively and postoperatively	Transfusion requirements intraoperatively and postoperatively through study completion	during hospitalization, up to 8 days
Other	Inotropic score	Inotropic score Calculation of Inotropic score (IS) and Vasoactive inotropic score (VIS). IS(a) = dopamine dose (lg/kg/min) ? dobutamine dose (lg/kg/min) ? 100 9 epinephrine dose (lg/kg/min) VIS(b) = IS ? 10 9 milrinone dose (lg/kg/ min) ? 10,000 9 vasopressin dose (U/kg/ min) ? 100 9 norepinephrine dose (lg/kg/min) IS inotrope score, VIS vasoactive-inotropic score	at 5 days post operative
Primary	Acute kidney injury state II/III by AKIN criteria	Acute kidney injury state II/III by AKIN criteria	At 48 hours post-operative
Secondary	Urine output during post op	Urine output during post op	first 12 hours post op
Secondary	Urine output during post op	Urine output during post op	daily until 3 days post op
Secondary	Concentration of Delta serum cystatin C	Delta serum cystatin C	24 hours post CPB
Secondary	Acute kidney injury stage	Acute kidney injury stage Pediatric modified Acute Kidney Injury Network criteria (pAKIN) AKI Stage I-<0.5mL (milliliter)/kg/hour for 8 hours AKI Stage II-<0.5mL/kg/hour for 16 hours AKI Stage III-<0.3mL/kg/hour for 24 hours OR Anuria for 16 hours; Using serum creatinine and AKIN criteria	max point within post CPB 72 hours