Intravenous vs. Oral Hydration to Reduce the Risk of Post-Contrast Acute Kidney Injury After Intravenous Contrast-Enhanced Computed Tomography in Patients With Severe Chronic Kidney Disease (ENRICH): A Randomized Controlled Trial
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Odense University Hospital
- Enrollment
- 254
- Locations
- 1
- Primary Endpoint
- Incidence of PC-AKI
Study Overview
Brief Summary
The use of contrast media (CM) poses a risk of post-contrast acute kidney injury (PC-AKI), especially among patients chronic kidney disease (CKD). International guidelines recommend intravenous (IV) hydration with isotonic 0.9% NaCl for three-four hours pre-contrast and four-six hours post-contrast. Recent studies have proven that oral hydration or no hydration is non-inferior to IV hydration in patients with mild to moderate CKD (eGFR 30-60 mL/min/1.73 m2). However, no randomized controlled trials have evaluated alternative hydration methods against the guideline-recommended hydration protocol for the prevention of PC-AKI in high-risk patients with severe CKD (eGFR < 30 mL/min/1.73 m2).
Thus, the main focus of this trial is to evaluate IV hydration vs. oral hydration for their efficacy to prevent of PC-AKI in patients with severe CKD, who are scheduled for an elective contrast-enhanced CT-scan (CECT) with IV contrast-administration.
Our research hypotheses consist of the following:
- Oral hydration with bottled tap water is non-inferior to IV-hydration with isotonic 0.9% NaCl as renal prophylaxis to prevent PC-AKI in patients with severe CKD referred for an elective IV CECT.
- NGAL and cfDNA are early and precise plasma and urinary biomarkers of PC-AKI with excellent diagnostic and prognostic accuracy for PC-AKI, dialysis, renal adverse events, hospitalization, progression in CKD-symptoms, and all-cause mortality.
Detailed Description
Trial design:
This study is a pragmatic investigator-iniated, single-centre, open-labelled, parallel-group non-inferiority randomized controlled trial with two parallel arms. Patients will randomly be allocated to preventive treatment with IV hydration or oral hydration.
Participants and study setting:
The ENRICH-trial is conducted at Odense University Hospital (OUH), which is a tertiary health-care centre. The referral area covers the region of Southern Denmark, which corresponds to 1.25 million citizens in 22 municipalities of both urban and rural environment. The trial enrols high-risk patients with an eGFR < 30 mL/min/1.73 m2 scheduled for IV CECT using approximately 50-150 mL of CM (GE Healthcare, Omnipaque 500 mL, osmolality 350 mg I/mL).
The study population will consist of patients, who are referred for an elective IV CECT in the work-up for treatment of CVD (e.g., transaortic valve-implantation, ablation, endocarditis etc.) or suspected CVD (e.g., angina etc.), suspected cancer, thoracic/abdominal/urogenital diseases, or cardiovascular work-up before kidney transplantation. Patients referred for an acute or subacute IV CECT with competing etiologies for PC-AKI (e.g., sepsis, acute tubular necrosis, cardiogenic shock etc.) will not be considered eligible for inclusion.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Single (Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •eGFR < 30 mL/min/1.73 m2
- •Scheduled for elective IV CECT
- •Signed informed consent
Exclusion Criteria
- •Allergy to Iodine
- •Pregnancy
- •Active dialysis treatment
- •Acute infectious or inflammatory disease
- •Acute pre- and/or post-renal kidney failure
- •Unable to understand study information
Arms & Interventions
IV-hydration group (standard of care according to international guidelines)
The IV-hydration with isotonic 0.9% NaCl will be initiated three hours prior to the IV CECT and completed four hours after IV CECT (infusion rate of 1-3 mL/kg/hour). Patients are prescribed a fixed volume of 1000 mL, which is equally distributed before and after IV CECT (500 mL before and 500 mL after).
Patients with heart failure (LVEF ≤ 40%) are prescribed a reduced volume of 500 mL, which is also equally distributed before and after IV CECT (250 mL before and 250 mL after).
Intervention: Preventive treatment with IV-hydration (Other)
Oral hydration group
The oral hydration regimen will be initiated one-two hours prior to IV CECT and completed within four hours after IV CECT. Patients are prescribed a fixed volume of 1000 mL, which is distributed equally before and after IV CECT (500 mL before and 500 mL after).
Patients with heart failure (LVEF ≤ 40%) are prescribed a reduced volume of 500 mL, which is equally distributed before and after IV CECT (250 mL before and 250 mL after).
Intervention: Preventive treatment with oral hydration (Other)
Outcomes
Primary Outcomes
Incidence of PC-AKI
Time Frame: 2-5 days after IV CECT
The incidence of PC-AKI within the two arms
Secondary Outcomes
- The diagnostic and prognostic accuracy of plasma and urinary NGAL and cell-free DNA(In-hospital: Before initiation of the hydration protocol and the IV CECT (baseline) and 4 hours after IV CECT)
- Cost-effectiveness(1 day (at the day of the patient's scheduled cardiac CT))
- Time-effectiveness of the two hydration protocols.(In-hospital: Starting 1-3 hours before IV CECT and lasting maximally until 4 hours after IV CECT)
- Risk of PC-AKI according to the size of the kidneys(2-5 days after IV CECT)
- Incidence of new onset need for dialysis treatment(≤ 30 days after IV CECT)
- All-cause mortality(≤ 30 days after IV CECT)
- Hospitalization due to suspected hydration- or contrast-related sequelae(≤ 30 days after IV CECT)
- Mean changes in eGFR.(eGFR is measured on the following time-points (days from baseline): -89 to -seven days, -six to -four days, -three to -one days, 0 days (baseline), +two to three days, +four to five days, and +25 to +40 days)
- The effect of hydration on standard blood parameters(Standard blood parameters will be obtained after IV CECT at +two to three days and/or +four to five days, and +25 to +40 days from baseline)
- Renal adverse events(25-40 days after IV CECT)
- Progression in CKD-symptoms(≤ 30 days after IV CECT)
- Incidence of PC-AKI based on the criteria from the previously used and most cited definition of PC-AKI(2-5 days after IV CECT)
- Hospitalization due to symptomatic heart failure(≤ 30 days after IV CECT)
- Mean changes in SCr(SCr is measured on the following time-points (days from baseline): -89 to -seven days, -six to -four days, -three to -one days, 0 days (baseline), +two to three days, +four to five days, and +25 to +40 days)
- Mean values of plasma and urinary NGAL and cell-free DNA(In-hospital: Before initiation of the hydration protocol and the IV CECT (baseline) and 4 hours after IV CECT)
- Timepoints of diagnosis for PC-AKI(2-5 days after IV CECT)
- Number of patients with normalization of PC-AKI(≤ 40 days after IV CECT)
- Mean changes of plasma and urinary NGAL and cell-free DNA(In-hospital: Before initiation of the hydration protocol and the IV CECT (baseline) and 4 hours after IV CECT)
Investigators
Emil Johannes Ravn
Medical student and clinical research assistant
Odense University Hospital