Clinical trial NCT04936607: ImproviNg rEnal Outcomes Following Coronary angiograPhy and/or percuTaneoUs coroNary intErventions
Official title: ImproviNg rEnal Outcomes Following Coronary angiograPhy and/or percuTaneoUs coroNary intErventions: a Pragmatic, Adaptive, Patient-oriented Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Contrast-Induced Acute Kidney Injury
Keywords: Randomized controlled trial
Pragmatic trial
Adaptive trial
Patient-oriented trial
Contrast-induced Nephropathy
Acute Kidney Injury
Coronary angiography
Percutaneous coronary intervention
Lead sponsor: Montreal Heart Institute
Sponsor class: OTHER
Collaborators: name: Université de Montréal
name: Canadian Institutes of Health Research (CIHR)
First posted: 2021-06-23
Enrollment: 1158
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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).

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.

Eligibility criteria: 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%.

Primary outcomes:
measure: Contrast-induced acute kidney injury
timeFrame: 7 days
Secondary outcomes:
measure: Major adverse renal and cardiovascular events (MARCE)
timeFrame: 6 months
measure: MARCE composite with the addition of persistent increase of at least 50% from baseline serum creatinine
timeFrame: 6 months
measure: All-cause death
timeFrame: 6 months
measure: Myocardial infarction
timeFrame: 6 months
measure: Stroke
timeFrame: 6 months
measure: Renal replacement therapy
timeFrame: 6 months
measure: Chronic kidney disease
timeFrame: 6 months
measure: Worsening of kidney disease
timeFrame: 6 months
measure: Hospital length-of-stay
timeFrame: 6 months
Other outcomes:
Locations:
city: Montréal
country: Canada
facility: Montreal Heart Institute
state: Quebec
Study officials:
affiliation: Montreal Heart Institute
name: Guillaume Marquis-Gravel, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: