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

Contrast-Induced Acute Kidney Injury Clinical Trial

— NEPTUNE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04936607
• Other study ID #: ICM 2022-2949
• Status: Recruiting
• Phase: N/A
• Start date: June 28, 2021
• Est. completion date: July 31, 2027

Study information

• Verified date: August 2023
• Source: Montreal Heart Institute
• Contact: Guillaume Marquis-Gravel, MD, MSc
• Phone: (514) 376-3330
• Email: guillaume.marquis.gravel[@]umontreal.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1158
• Est. completion date: July 31, 2027
• Est. primary completion date: January 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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%.

Related Conditions & MeSH terms

• Acute Kidney Injury
• Contrast-Induced Acute Kidney Injury

Intervention

Procedure:
• Personalized hydration strategy
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.
• Standard of care
In the control group, infusion rate will be of 1.5 ml/kg/h during the procedure, and for the 4 following hours.

Locations

Country	Name	City	State
Canada	Montreal Heart Institute	Montréal	Quebec

Sponsors (3)

Lead Sponsor	Collaborator
Montreal Heart Institute	Canadian Institutes of Health Research (CIHR), Université de Montréal

Country where clinical trial is conducted

Canada, 

Outcome

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