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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Contrast-Induced Acute Kidney Injury
• Intervention / Treatment: Procedure: Personalized hydration strategy; Procedure: Standard of care

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 1158
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Guillaume Marquis-Gravel, MD, MSc; Phone Number: (514) 376-3330; Email: guillaume.marquis.gravel@umontreal.ca

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H1T1C8
      • Recruiting
      • Montreal Heart Institute
      • Contact: Guillaume Marquis-Gravel, MD, MSc; Phone Number: 9195193271; Email: guillaume.marquis.gravel@umontreal.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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%.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Personnalized 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.	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.
Active Comparator: 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.	Procedure: 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.

What is the study measuring?

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
All-cause death	All-cause death	6 months
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
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

Collaborators and Investigators

• Sponsor: Montreal Heart Institute
• Collaborators: Canadian Institutes of Health Research (CIHR); Université de Montréal
• Investigators: Principal Investigator: Guillaume Marquis-Gravel, MD, MSc, Montreal Heart Institute

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2021
• Primary Completion (Estimated): January 30, 2027
• Study Completion (Estimated): July 31, 2027

Study Registration Dates

• First Submitted: June 15, 2021
• First Submitted That Met QC Criteria: June 15, 2021
• First Posted (Actual): June 23, 2021

Study Record Updates

• Last Update Posted (Actual): December 8, 2025
• Last Update Submitted That Met QC Criteria: December 1, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Coronary angiography; Randomized controlled trial; Percutaneous coronary intervention; Acute Kidney Injury; Adaptive trial; Pragmatic trial; Contrast-induced Nephropathy; Patient-oriented trial
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Renal Insufficiency; Acute Kidney Injury; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care
• Other Study ID Numbers: ICM 2022-2949

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No IPD sharing plan.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No