Sodium Chloride and Contrast Nephropathy (PNIC-Na)

Efficacy of Oral Sodium Chloride vs iv Sodium Chloride in the Prevention of Contrast Nephropathy in Outpatients

This phase II, open, non-inferiority, randomized and controlled clinical trial is aimed to ascertain the incidence of contrast nephropathy in outpatients undergoing CT scan with contrast.

Patients will be randomized to receive oral prophylaxis with capsules of sodium chloride and free water ingestion or prophylaxis with sodium chloride 0.9% intravenous solution.

The total dose (mmol) of sodium chloride will be the same regardless administration via. The contrast will be iodixanol.

Patients >65 years, of both sexes, with at least one of the following criteria: diabetes, stable heart failure or chronic kidney disease (estimated glomerular filtration rate between 30 and 60 ml/min), undergoing CT scan with contrast, and who give written informed consent, will be included in the study. Patients with estimated glomerular filtration rate <30 ml/min, serum potassium <3.5 mEq/L, infusion of iodine contrast in the previous 15 days, administration of nephrotoxic drugs in the previous 72 hours or expected in the following hours after contrast infusion, decompensated chronic conditions (heart failure, chronic obstructive pulmonary disease, hypertension), allergy to iodine contrast, or the presence of hyperchloremia or hypernatremia, will be excluded from the study.

Contrast nephropathy will be defined as the increase of serum creatinine >0.3 mg/dL from baseline, or the reduction of estimated glomerular filtration rate (MDRD-4) >25% from baseline, in the first 48 hours after contrast administration.

Study Overview

• Status: Completed
• Conditions: Heart Failure; Diabetes; Kidney Failure, Chronic; Kidney Failure, Acute
• Intervention / Treatment: Drug: Oral sodium chloride; Drug: Intravenous sodium chloride

Detailed Description

This phase II, open, non-inferiority, randomized and controlled clinical trial is aimed to ascertain the incidence of contrast nephropathy in outpatients undergoing CT scan with contrast.

Patients will be randomized to receive oral prophylaxis with capsules of sodium chloride and free water ingestion or prophylaxis with sodium chloride 0.9% intravenous solution.

In those patients randomly allocated to oral prophylaxis (n=133), patients will receive capsules of sodium chloride and free water ingestion (for each capsule of sodium chloride, patients will take 250 ml of water, assuring a minimum ingestion of 750 ml of water) in the 48 hours prior contrast injection. Patients will take capsules of sodium chloride at a dose of 100 mg/kg during 48 hours previous the injection of contrast (48, 40, 32, 24, 16, and 8 hours), at the moment of contrast injection and 12 hours after the injection of contrast. In those patients randomly allocated to receive sodium chloride 0.9% intravenous solution (n=133), patients will receive at hospital 3 ml/Kg of sodium chloride 0.9%, one hour previous contrast injection and 2 ml/kg during the 4 hours after contrast injection. The total dose (mmol) of sodium chloride will be the same regardless administration via. The contrast will be iodixanol (320 mg of iodine/ml, in 100 ml, at an infusion rate of 2-5 ml/sec).

Patients >65 years, of both sexes, with at least one of the following criteria: diabetes, stable heart failure or chronic kidney disease (estimated glomerular filtration rate between 30 and 60 ml/min), undergoing CT scan with contrast, and who give written informed consent, will be included in the study. Patients with estimated glomerular filtration rate <30 ml/min, serum potassium <3.5 mEq/L, infusion of iodine contrast in the previous 15 days, administration of nephrotoxic drugs in the previous 72 hours or expected in the following hours after contrast infusion, decompensated chronic conditions (heart failure, chronic obstructive pulmonary disease, hypertension), allergy to iodine contrast, or the presence of hyperchloremia or hypernatremia, will be excluded from the study.

Contrast nephropathy will be defined as the increase of serum creatinine >0.3 mg/dL from baseline, or the reduction of estimated glomerular filtration rate (MDRD-4) >25% from baseline, in the first 48 hours after contrast administration.

• Study Type: Interventional
• Enrollment (Actual): 271
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients >65 years,
• Both sexes,
• With at least one of the following criteria: diabetes or stable heart failure or chronic kidney disease (estimated glomerular filtration rate between 30 and 60 ml/min),
• Undergoing CT scan with contrast
• Written informed consent.

Exclusion Criteria:

• Estimated glomerular filtration rate <30 ml/min,
• Serum potassium <3.5 mEq/L,
• Infusion of iodine contrast in the previous 15 days,
• Administration of nephrotoxic drugs in the previous 72 hours or expected in the following hours after contrast infusion,
• Decompensated chronic conditions (heart failure, chronic obstructive pulmonary disease, hypertension),
• Allergy to iodine contrast,
• Presence of hyperchloremia or hypernatremia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral sodium chloride; Patients will receive capsules of sodium chloride and free water ingestion (for each capsule of sodium chloride, patients will take 250 ml of water, assuring a minimum ingestion of 750 ml of water) in the 48 hours prior contrast injection. Patients will take capsules of sodium chloride at a dose of 100 mg/kg during 48 hours previous the injection of contrast (48, 40, 32, 24, 16, and 8 hours), at the moment of contrast injection and 12 hours after the injection of contrast.	Drug: Oral sodium chloride; Patients will receive capsules of sodium chloride and free water ingestion (for each capsule of sodium chloride, with 250 ml of water, assuring a minimum ingestion of 750 ml of water) in the 48 hours prior contrast injection. Patients will take capsules of sodium chloride at a dose of 100 mg/kg during 48 hours previous the injection of contrast (48, 40, 32, 24, 16, and 8 hours), at the moment of contrast injection and 12 hours after the injection of contrast.
Active Comparator: Intravenous sodium chloride; Patients will receive at hospital 3 ml/Kg of sodium chloride 0.9%, one hour previous contrast injection and 2 ml/kg during the 4 hours after contrast injection.	Drug: Intravenous sodium chloride; Patients will receive at hospital 3 ml/Kg of sodium chloride 0.9%, one hour previous contrast injection and 2 ml/kg during the 4 hours after contrast injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Acute Kidney Injury During the First 48 Hours After Contrast Administration	Contrast-Associated Acute Kidney Injury, defined as the increase of serum creatinine >0.3 mg/dL from baseline, or the reduction of estimated glomerular filtration rate (MDRD-4) >25%, within 48h after contrast administration	Within 48h after contrast administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estimated Glomerular Filtration Rate (eGFR) at 24h From Baseline	Estimated glomerular filtration rate (eGFR) according to MDRD-4 at 24 hours from contrast administration (baseline), as an secondary efficacy laboratory assessment.	24 hours from contrast administration (baseline)
Estimated Glomerular Filtration Rate (eGFR) at 48h From Baseline	Estimated glomerular filtration rate (eGFR) according to MDRD-4 at 48 hours from contrast administration (baseline), as an secondary efficacy laboratory assessment.	48 hours from contrast administration (baseline)
Serum Creatinine at 24h From Baseline	Serum creatinine at 24 hours from contrast administration (baseline), as an secondary efficacy laboratory assessment.	24 hours from contrast administration (baseline)
Serum Creatinine at 48h From Baseline	Serum creatinine at 48 hours from contrast administration (baseline), as an secondary efficacy laboratory assessment.	48 hours from contrast administration (baseline)
Cystatin C at 24h From Baseline	Cystatin C at 24 hours from contrast administration (baseline), as an secondary efficacy laboratory assessment.	24 hours from contrast administration (baseline)
Cystatin C at 48h From Baseline	Cystatin C at 48 hours from contrast administration (baseline), as an secondary efficacy laboratory assessment.	48 hours from contrast administration (baseline)
Albumin-to-creatinine Ratio at 24h From Baseline	Albumin-to-creatinine ratio at 24 hours from contrast administration (baseline), as an secondary efficacy laboratory assessment.	24 hours from contrast administration (baseline)
Albumin-to-creatinine Ratio at 48h From Baseline	Albumin-to-creatinine ratio at 48 hours from contrast administration (baseline), as an secondary efficacy laboratory assessment.	48 hours from contrast administration (baseline)
Urea at 24h From Baseline	Urea at 24 hours from contrast administration (baseline), as an secondary efficacy laboratory assessment.	24 hours from contrast administration (baseline)
Urea at 48h From Baseline	Urea at 48 hours from contrast administration (baseline), as an secondary efficacy laboratory assessment.	48 hours from contrast administration (baseline)
Serum Sodium at 24h From Baseline	Serum sodium at 24 hours from contrast administration (baseline), as an secondary efficacy laboratory assessment.	24 hours from contrast administration (baseline)
Serum Sodium at 48h From Baseline	Serum sodium at 48 hours from contrast administration (baseline), as an secondary efficacy laboratory assessment.	48 hours from contrast administration (baseline)
Serum Potassium at 24h From Baseline	Serum potassium at 24 hours from contrast administration (baseline), as an secondary efficacy laboratory assessment.	24 hours from contrast administration (baseline)
Serum Potassium at 48h From Baseline	Serum potassium at 48 hours from contrast administration (baseline), as an secondary efficacy laboratory assessment.	48 hours from contrast administration (baseline)

Collaborators and Investigators

• Sponsor: Hospital Universitario Ramon y Cajal
• Collaborators: Instituto de Salud Carlos III; Ministerio de Sanidad, Servicios Sociales e Igualdad
• Investigators: Principal Investigator: Luis Manzano, MD, PhD, Hospital Universitario Ramon y Cajal

Publications and helpful links

General Publications

• Suarez Carantona C, Escobar Cervantes C, Fabregate M, Lopez Rodriguez M, Bara Ledesma N, Soto Perez-Olivares J, Ruiz Ortega RA, Lopez Castellanos G, Olavarria Delgado A, Blazquez Sanchez J, Gomez Del Olmo V, Moralejo Martin M, Pumares Alvarez MB, Sanchez Gallego MC, Llacer P, Liano F, Manzano L. Oral Sodium Chloride in the Prevention of Contrast-Associated Acute Kidney Injury in Elderly Outpatients: The PNIC-Na Randomized Non-Inferiority Trial. J Clin Med. 2023 Apr 19;12(8):2965. doi: 10.3390/jcm12082965.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2014
• Primary Completion (Actual): November 29, 2019
• Study Completion (Actual): November 29, 2019

Study Registration Dates

• First Submitted: March 17, 2018
• First Submitted That Met QC Criteria: March 22, 2018
• First Posted (Actual): March 26, 2018

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 14, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Acute kidney failure; CT scan; Sodium chloride; Iodine contrast
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency, Chronic; Acute Kidney Injury; Renal Insufficiency; Kidney Failure, Chronic
• Other Study ID Numbers: EC11-132

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data Availability Statement The data presented in this study are available on request from the corresponding author. The data are not publicly available due to participant confidentiality.
• IPD Sharing Time Frame: After revision and approval of the principal investigator.
• IPD Sharing Access Criteria: Approval of the principal investigator.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No