Personalized Hydration Strategy for Acute Kidney Injury

(NEPTUNE Trial)

Overseen By Guillaume Marquis-Gravel, MD, MSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Guillaume Marquis-Gravel

Disqualifiers: Shock, Emergent procedures, Iodine contrast, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

1158 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this 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).

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is the personalized hydration strategy for acute kidney injury safe for humans?

Research shows that personalized hydration strategies, like those guided by urine flow rate or left ventricular end-diastolic pressure, are generally safe for preventing kidney injury in patients undergoing heart procedures. These strategies do not significantly increase the risk of pulmonary edema (fluid in the lungs), suggesting they are safe for use in humans. ^{1 2 3 4 5}

How is the personalized hydration strategy treatment different from other treatments for acute kidney injury?

The personalized hydration strategy is unique because it tailors the hydration process based on individual patient factors like left ventricular end-diastolic pressure (a measure of heart function), contrast volume, and baseline kidney function, rather than using a fixed-rate approach. This method aims to optimize hydration to prevent kidney injury more effectively by considering each patient's specific needs. ^{1 2 6 7 8}

What data supports the effectiveness of the treatment Personalized Hydration Strategy for Acute Kidney Injury?

Research shows that personalized hydration strategies, such as those guided by urine flow rate and central venous pressure, are more effective in preventing acute kidney injury compared to fixed-rate hydration. These tailored approaches help reduce the risk of kidney damage after procedures like coronary interventions. ^{1 2 6 7 9}

Who Is on the Research Team?

Guillaume Marquis-Gravel, MD

Principal Investigator

Montreal Heart Institute

Are You a Good Fit for This Trial?

This trial is for adults over 18 who are about to have a heart procedure like coronary angiogram or PCI and can attend follow-up visits. They should expect to live at least 6 more months. It's not for those in shock, having emergency procedures, recent contrast media exposure, severe heart valve disease, very weak hearts (LVEF <30%), or current kidney issues.

Inclusion Criteria

Willingness to participate and to attend study visits

I am scheduled for a heart artery examination and/or treatment.

You are expected to live for at least 6 more months.

Exclusion Criteria

You have an intra-aortic balloon pump (IABP) in place.

I do not have shock related to heart problems or other causes at the time of the procedure.

I have had an emergency procedure for a heart attack.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a personalized or standard hydration strategy during and after coronary angiogram and/or PCI

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with serum creatinine measured at 48 hours, 7 days, and 6 months

6 months

Multiple visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Personalized hydration strategy
• Standard of care

Trial Overview NEPTUNE is testing a new IV hydration method against the usual care to prevent kidney damage after heart imaging tests or treatments. The new method considers heart pressure readings, contrast amount used, and initial kidney function. Patients are randomly assigned to either group without knowing which one they're in.

How Is the Trial Designed?

Group I: Personnalized hydration strategy Experimental Treatment 1 Intervention

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.

Group II: Standard of care Active Control 1 Intervention

In the control group, infusion rate will be of 1.5 ml/kg/h during the procedure, and for the 4 following hours.

Who Is Running the Clinical Trial?

Guillaume Marquis-Gravel

Lead Sponsor

Trials

1

Recruited

1,200+

Montreal Heart Institute

Lead Sponsor

Trials

125

Recruited

85,400+

Université de Montréal

Collaborator

Trials

223

Recruited

104,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Published Research Related to This Trial

A systematic review of 8 randomized controlled trials with 2312 patients found that tailored hydration strategies, particularly urine flow rate-guided hydration, significantly reduce the incidence of contrast-induced acute kidney injury (CI-AKI) compared to fixed-rate hydration.

No significant difference in the incidence of pulmonary edema was observed between tailored and fixed hydration strategies, indicating that tailored approaches are both effective in preventing CI-AKI and safe regarding pulmonary complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tailored Versus Standard Hydration to Prevent Acute Kidney Injury After Percutaneous Coronary Intervention: Network Meta-Analysis. Moroni, F., Baldetti, L., Kabali, C., et al.[2021]

In a study of 114 patients with chronic kidney disease undergoing cardiac procedures, LVEDP-guided hydration did not significantly reduce the incidence of contrast-induced acute kidney injury (CI-AKI) compared to standard hydration methods.

Both hydration strategies were safe, with no major adverse cardiac events or deaths reported during hospitalization or the 30-day follow-up period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left ventricular end-diastolic pressure-guided hydration for the prevention of contrast-induced acute kidney injury in patients with stable ischemic heart disease: the LAKESIDE trial. Marashizadeh, A., Sanati, HR., Sadeghipour, P., et al.[2020]

In a study of 551 patients with advanced congestive heart failure undergoing coronary procedures, higher hydration volumes (over 15 mL/kg) were linked to increased risks of contrast-induced acute kidney injury (CI-AKI) and worsening heart failure (WHF).

The findings suggest that while hydration is important, excessive volumes can lead to serious complications, indicating a need for personalized hydration strategies in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal hydration volume among high-risk patients with advanced congestive heart failure undergoing coronary angiography. Chen, SQ., Liu, Y., Bei, WJ., et al.[2019]

Aggressive hydration significantly reduced the occurrence of contrast-induced acute kidney injury (CI-AKI) in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI), with rates of 21.8% compared to 31.1% in the general hydration group.

The aggressive hydration method was found to be safe, with no significant difference in the incidence of acute heart failure between the two groups (8.1% vs 6.4%), indicating that this approach can effectively prevent CI-AKI without increasing the risk of heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hydration for prevention of kidney injury after primary coronary intervention for acute myocardial infarction: a randomised clinical trial. Liu, Y., Tan, N., Huo, Y., et al.[2022]

In a study of 6682 acute kidney injury patients, 36.8% were identified as volume-responsive, showing increased urine output after receiving more than 5 liters of fluid, highlighting the importance of fluid management in AKI treatment.

The machine learning model (XGBoost) significantly outperformed traditional logistic regression in predicting which patients would respond to fluid intake, indicating that advanced predictive modeling can enhance decision-making in critical care settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Machine learning for the prediction of volume responsiveness in patients with oliguric acute kidney injury in critical care. Zhang, Z., Ho, KM., Hong, Y.[2020]

The REMEDIAL III trial will compare two hydration strategies—UFR-guided and LVEDP-guided—to prevent contrast-induced acute kidney injury (CIAKI) in 700 high-risk patients, focusing on their effectiveness in maintaining kidney function after contrast media exposure.

The primary outcome will assess the occurrence of CIAKI and acute pulmonary edema, providing insights into which hydration method is more effective in protecting kidney health during medical imaging procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Renal insufficiency following contrast media administration trial III: Urine flow rate-guided versus left-ventricular end-diastolic pressure-guided hydration in high-risk patients for contrast-induced acute kidney injury. Rationale and design. Briguori, C., D'Amore, C., De Micco, F., et al.[2020]

In a study of 1,307 patients with renal insufficiency and heart failure, higher hydration volumes relative to body weight (HV/W) were linked to increased rates of contrast-induced acute kidney injury (CI-AKI) and worsening heart failure (WHF), indicating that too much hydration can be harmful.

Excessively high HV/W ratios were associated with a significantly increased risk of long-term mortality, suggesting that careful management of hydration is crucial for patients undergoing coronary procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safe Hydration to Prevent Contrast-Induced Acute Kidney Injury and Worsening Heart Failure in Patients with Renal Insufficiency and Heart Failure Undergoing Coronary Angiography or Percutaneous Coronary Intervention. Bei, WJ., Wang, K., Li, HL., et al.[2019]

The REMEDIAL III trial will investigate two hydration strategies to prevent contrast-induced nephropathy (CIN) in 700 high-risk patients undergoing angiographic procedures, focusing on urine output and left ventricular end diastolic pressure (LVEDP) as guides.

Understanding the optimal timing, dose, and duration of hydration could significantly improve patient safety and reduce the incidence of CIN, which is a major cause of complications in these procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does the method of administering fluids matter for contrast-induced nephropathy? REMEDIAL III compares LVEDP versus urine flow-guided hydration. Grines, CL., Marshall, JJ.[2020]

Prophylactic hydration is effective in preventing acute kidney injury when the volume of contrast medium administered exceeds 100 mL, with an odds ratio of 0.546 indicating a significant benefit.

For contrast volumes less than 100 mL, hydration does not show efficacy in preventing kidney injury, suggesting it may not be necessary in these cases regardless of the patient's kidney function or method of administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Contrast Medium Volume to Guide Prophylactic Hydration to Prevent Acute Kidney Injury After Contrast Administration: A Meta-Analysis. Lee, HC., Chuang, KI., Lu, CF., et al.[2020]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Tailored Versus Standard Hydration to Prevent Acute Kidney Injury After Percutaneous Coronary Intervention: Network Meta-Analysis. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Left ventricular end-diastolic pressure-guided hydration for the prevention of contrast-induced acute kidney injury in patients with stable ischemic heart disease: the LAKESIDE trial. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Optimal hydration volume among high-risk patients with advanced congestive heart failure undergoing coronary angiography. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Hydration for prevention of kidney injury after primary coronary intervention for acute myocardial infarction: a randomised clinical trial. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Machine learning for the prediction of volume responsiveness in patients with oliguric acute kidney injury in critical care. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Renal insufficiency following contrast media administration trial III: Urine flow rate-guided versus left-ventricular end-diastolic pressure-guided hydration in high-risk patients for contrast-induced acute kidney injury. Rationale and design. [2020]

7. Japan pubmed.ncbi.nlm.nih.gov

Safe Hydration to Prevent Contrast-Induced Acute Kidney Injury and Worsening Heart Failure in Patients with Renal Insufficiency and Heart Failure Undergoing Coronary Angiography or Percutaneous Coronary Intervention. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Does the method of administering fluids matter for contrast-induced nephropathy? REMEDIAL III compares LVEDP versus urine flow-guided hydration. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Use of Contrast Medium Volume to Guide Prophylactic Hydration to Prevent Acute Kidney Injury After Contrast Administration: A Meta-Analysis. [2020]