ImproviNg rEnal Outcomes Following Coronary angiograPhy and/or percuTaneoUs coroNary intErventions

Study Overview
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Brief Summary
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The NEPTUNE triple-blind, active-placebo, adaptive, pragmatic, randomized trial aims to evaluate the effectiveness of a new intra-venous hydration strategy guided by left ventricular end-diastolic pressure (LVEDP), amount of contrast used, and baseline renal function, to prevent contrast-induced acute kidney injury (CI-AKI) and patient-oriented clinical endpoints in all-comer patients undergoing coronary angiogram and/or percutaneous coronary intervention (PCI).

Detailed Description
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All-comer patients undergoing a coronary angiogram and/or a PCI and meeting the eligibility criteria will be randomized to be treated with either a hydration strategy personalized to LVEDP, amount of contrast used, and baseline renal function, or to standard, non-tailored hydration (1:1 allocation ratio stratified by GFR ≥60 vs. <60 mL/min/1.73 m2). The operators (interventional cardiologists and fellows) and the participants will be blinded to the treatment allocation during the procedure. Serum creatinine will be measured at 48 hours, 7 days, and 6 months after the procedure, and the incidence of contrast-induced acute kidney injury (CI-AKI) (primary endpoint) and of major adverse renal and cardiovascular events will be evaluated by a blinded and independent expert adjudication committee. All participants will be treated with a commercially available 0.9% NaCl solution (normal saline, NS) infusion at a rate of 3 mL/kg/h for one hour prior to the procedure. In both study groups, LVEDP will be measured at the beginning of the procedure by introducing a catheter in the left ventricle, as performed routinely in clinical practice. In the experimental group, NS infusion rate will be adjusted based on LVEDP for the whole duration of the procedure (<13 mmHg: 5 ml/kg/h; 13-18 mmHg: 3 ml/kg/h; >18 mmHg: 1.5 ml/kg/h), or for one hour, whichever is the longest. After the procedure, and for a duration of 4 hours, the hydration rate will be adjusted based on the (contrast volume:estimated glomerular filtration rate (eGFR)) ratio, according to the following scheme: 1.5 ml/kg/h if contrast volume/eGFR ratio <2.0; 3 ml/kg/h for contrast volume/eGFR ratio 2.0-2.9; 5 ml/kg/h for contrast volume/eGFR ratio ≥3.0. In the control group, infusion rate will be of 1.5 ml/kg/h during the procedure, and for the 4 following hours. This study will follow an adaptive design in which the primary endpoint will be shifted to a more patient-oriented endpoint at the time of a single interim analysis according to pre-specified criteria established in the protocol. The adaptive design will allow to stop the trial if the experimental strategy is futile to reduce the rates of CI-AKI, and to continue on an operationally seamless manner if the experimental strategy is beneficial to reduce CI-AKI, transitioning to major adverse renal and cardiovascular endpoints (MARCE) as the primary endpoint.

Official Title
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ImproviNg rEnal Outcomes Following Coronary angiograPhy and/or percuTaneoUs coroNary intErventions: a Pragmatic, Adaptive, Patient-oriented Randomized Controlled Trial

Conditions
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Contrast-Induced Acute Kidney Injury

Intervention / Treatment
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* Procedure: Personalized hydration strategy
* Procedure: Standard of care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years; Planned coronary angiogram and/or PCI; Willingness to participate and to attend study visits; Expected life expectancy ≥6 months. Exclusion Criteria: Cardiogenic or non-cardiogenic shock at the time of the procedure; Emergent procedures (e.g. STEMI); Iodine-based contrast media received within 2 days; Presence of Intra-Aortic Balloon Pump (IABP); Cardiac arrest within 24 hours; Pre-procedural AKI defined using the modified KDIGO criteria within 7 days; Renal replacement therapy; Severe aortic or mitral disease; LVEF <30%.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Personnalized hydration strategy<br>In the experimental group, NS infusion rate will be adjusted based on LVEDP for the whole duration of the procedure (<13 mmHg: 5 ml/kg/h; 13-18 mmHg: 3 ml/kg/h; >18 mmHg: 1.5 ml/kg/h), or for one hour, whichever is the longest. After the procedure, and for a duration of 4 hours, the hydration rate will be adjusted based on the (contrast volume:estimated glomerular filtration rate (eGFR)) ratio, according to the following scheme: 1.5 ml/kg/h if contrast volume/eGFR ratio <2.0; 3 ml/kg/h for contrast volume/eGFR ratio 2.0-2.9; 5 ml/kg/h for contrast volume/eGFR ratio ≥3.0. | Procedure: Personalized hydration strategy<br>* In the experimental group, NS infusion rate will be adjusted based on LVEDP for the whole duration of the procedure (<13 mmHg: 5 ml/kg/h; 13-18 mmHg: 3 ml/kg/h; >18 mmHg: 1.5 ml/kg/h), or for one hour, whichever is the longest. After the procedure, and for a duration of 4 hours, the hydration rate will be adjusted based on the (contrast volume:estimated glomerular filtration rate (eGFR)) ratio, according to the following scheme: 1.5 ml/kg/h if contrast volume/eGFR ratio <2.0; 3 ml/kg/h for contrast volume/eGFR ratio 2.0-2.9; 5 ml/kg/h for contrast volume/eGFR ratio ≥3.0.<br>|
| Active Comparator: Standard of care<br>In the control group, infusion rate will be of 1.5 ml/kg/h during the procedure, and for the 4 following hours. | Procedure: Standard of care<br>* In the control group, infusion rate will be of 1.5 ml/kg/h during the procedure, and for the 4 following hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Contrast-induced acute kidney injury | Increase in creatinine of 1.5 times baseline within 7 days or increase in creatinine by 26.5 umol/L (i.e. 0.3 mg/dL) within 48 hours | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major adverse renal and cardiovascular events (MARCE) | Composite of death, myocardial infarction, stroke, or renal replacement therapy | 6 months | 
| MARCE composite with the addition of persistent increase of at least 50% from baseline serum creatinine | MARCE composite with the addition of persistent increase of at least 50% from baseline serum creatinine | 6 months | 
| All-cause death | All-cause death | 6 months | 
| Myocardial infarction | Myocardial infarction (types 1-5) | 6 months | 
| Stroke | Ischemic, hemorrhagic, or undetermined stroke | 6 months | 
| Renal replacement therapy | Any type of renal replacement therapy (dialysis, hemofiltration, hemodiafiltration, or other) | 6 months | 
| Chronic kidney disease | 50% increase from baseline serum creatinine | 6 months | 
| Worsening of kidney disease | Transition to a higher KDIGO CKD stage | 6 months | 
| Hospital length-of-stay | Hospital length-of-stay after the procedure | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Randomized controlled trial, Pragmatic trial, Adaptive trial, Patient-oriented trial, Contrast-induced Nephropathy, Acute Kidney Injury, Coronary angiography, Percutaneous coronary intervention