A Phase 3 interventional study of Aminophylline and Placebo in Acute Kidney Injury, sponsored by Le Bonheur Children's Hospital. Status unknown at 2 sites in United States. Open to participants aged Up to 18 Years. Per ClinicalTrials.gov, last updated 2022-04-18.
Sponsored by Le Bonheur Children's Hospital · Phase 3, Interventional, and Treatment
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.
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.
1,595 studies on the registry are indexed under Acute Kidney Injury; 371 are open to participants now.
This study's planned enrollment of 80 is below the median of 100 across 763 interventional studies indexed under Acute Kidney Injury.
Browse Acute Kidney Injury studies →Le Bonheur Children's Hospital is the lead sponsor of 20 studies on the registry; 3 are open to participants now.
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Cohort 1
Cohort 2:
Exclusion Criteria:
Drug: Aminophylline
Drug: Placebo
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.
The placebo group will not receive any aminophylline treatments for the first post-op five days
Also known as: Normal Saline
Acute kidney injury state II/III by AKIN criteria
Acute kidney injury state II/III by AKIN criteria
Time frame: At 48 hours post-operative
Urine output during post op
Urine output during post op
Time frame: first 12 hours post op
Urine output during post op
Urine output during post op
Time frame: daily until 3 days post op
Concentration of Delta serum cystatin C
Delta serum cystatin C
Time frame: 24 hours post CPB
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
Time frame: max point within post CPB 72 hours
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.
Time frame: at 2 hours post CPB.
Time to extubation (hours)
Time to extubation (hours) number of hours post surgery
Time frame: during hospitalization, up to 8 days
Time to chest closure (hours)
Time to chest closure (hours) from start time of incision to chest closure during procedure
Time frame: during hospitalization, up to 3 days
Time to discharge from cardiovascular intensive care unit (CVICU) (days)
Time to discharge from CVICU (days)
Time frame: during hospitalization, approximate 5 days
Duration of hospital stay (Days).
Duration of hospital stay (Days).
Time frame: during hospitalization, approximate 8 days
Dialysis requirement (yes/no)
Dialysis requirement (yes/no)
Time frame: during hospitalization, approximate 5 days
Time to return to preoperative weight.
Time to return to preoperative weight.
Time frame: during hospitalization, approximate 8 days
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
Time frame: at 7 days post operative
Peritoneal dialysis catheter output.
Peritoneal dialysis catheter output through study completion
Time frame: during hospitalization, up to 8 days
Transfusion requirements intraoperatively and postoperatively
Transfusion requirements intraoperatively and postoperatively through study completion
Time frame: during hospitalization, up to 8 days
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
Time frame: at 5 days post operative
Plan to share: No
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