Sodium Chloride and Contrast Nephropathy

Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03476460
• Other study ID #: PNIC-Na
• Status: Completed
• Phase: Phase 2
• Start date: March 1, 2014
• Est. completion date: November 29, 2019

Study information

• Verified date: March 2020
• Source: Hospital Universitario Ramon y Cajal
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 269
• Est. completion date: November 29, 2019
• Est. primary completion date: November 29, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Kidney Injury
• Diabetes
• Heart Failure
• Kidney Failure, Acute
• Kidney Failure, Chronic
• Renal Insufficiency

Intervention

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.
• 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.

Locations

Country	Name	City	State
Spain	Hospital Universitario Ramon y Cajal	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Universitario Ramon y Cajal

Country where clinical trial is conducted

Spain, 

References & Publications (20)

Asif A, Epstein M. Prevention of radiocontrast-induced nephropathy. Am J Kidney Dis. 2004 Jul;44(1):12-24. Review. — View Citation

Aspelin P, Aubry P, Fransson SG, Strasser R, Willenbrock R, Berg KJ; Nephrotoxicity in High-Risk Patients Study of Iso-Osmolar and Low-Osmolar Non-Ionic Contrast Media Study Investigators. Nephrotoxic effects in high-risk patients undergoing angiography. — View Citation

Briguori C, Airoldi F, D'Andrea D, Bonizzoni E, Morici N, Focaccio A, Michev I, Montorfano M, Carlino M, Cosgrave J, Ricciardelli B, Colombo A. Renal Insufficiency Following Contrast Media Administration Trial (REMEDIAL): a randomized comparison of 3 prev — View Citation

Dussol B, Morange S, Loundoun A, Auquier P, Berland Y. A randomized trial of saline hydration to prevent contrast nephropathy in chronic renal failure patients. Nephrol Dial Transplant. 2006 Aug;21(8):2120-6. Epub 2006 Apr 12. — View Citation

Ferguson MA, Vaidya VS, Bonventre JV. Biomarkers of nephrotoxic acute kidney injury. Toxicology. 2008 Mar 20;245(3):182-93. doi: 10.1016/j.tox.2007.12.024. Epub 2008 Jan 4. Review. — View Citation

Gupta R, Gurm HS, Bhatt DL, Chew DP, Ellis SG. Renal failure after percutaneous coronary intervention is associated with high mortality. Catheter Cardiovasc Interv. 2005 Apr;64(4):442-8. — View Citation

Heinrich MC, Kuhlmann MK, Grgic A, Heckmann M, Kramann B, Uder M. Cytotoxic effects of ionic high-osmolar, nonionic monomeric, and nonionic iso-osmolar dimeric iodinated contrast media on renal tubular cells in vitro. Radiology. 2005 Jun;235(3):843-9. Epu — View Citation

Hojs R, Bevc S, Ekart R, Gorenjak M, Puklavec L. Serum cystatin C-based formulas for prediction of glomerular filtration rate in patients with chronic kidney disease. Nephron Clin Pract. 2010;114(2):c118-26. doi: 10.1159/000254384. Epub 2009 Nov 3. — View Citation

Hoshino A, Enomoto S, Kawahito H, Kurata H, Nakahara Y, Nakamura T. [Prevention of contrast-induced nephropathy using cardiac catheterization combined with hydration, oral N-acetylcysteine, sodium bicarbonate and iso-osmolar contrast agents]. J Cardiol. 2 — View Citation

Keyes R, Bagshaw SM. Early diagnosis of acute kidney injury in critically ill patients. Expert Rev Mol Diagn. 2008 Jul;8(4):455-64. doi: 10.1586/14737159.8.4.455. Review. — View Citation

McCullough PA, Stacul F, Becker CR, Adam A, Lameire N, Tumlin JA, Davidson CJ; CIN Consensus Working Panel. Contrast-Induced Nephropathy (CIN) Consensus Working Panel: executive summary. Rev Cardiovasc Med. 2006 Fall;7(4):177-97. — View Citation

Mehran R, Aymong ED, Nikolsky E, Lasic Z, Iakovou I, Fahy M, Mintz GS, Lansky AJ, Moses JW, Stone GW, Leon MB, Dangas G. A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: development and initial v — View Citation

Mehran R, Nikolsky E. Contrast-induced nephropathy: definition, epidemiology, and patients at risk. Kidney Int Suppl. 2006 Apr;(100):S11-5. Review. — View Citation

Merten GJ, Burgess WP, Gray LV, Holleman JH, Roush TS, Kowalchuk GJ, Bersin RM, Van Moore A, Simonton CA 3rd, Rittase RA, Norton HJ, Kennedy TP. Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA. 2004 — View Citation

Ozcan EE, Guneri S, Akdeniz B, Akyildiz IZ, Senaslan O, Baris N, Aslan O, Badak O. Sodium bicarbonate, N-acetylcysteine, and saline for prevention of radiocontrast-induced nephropathy. A comparison of 3 regimens for protecting contrast-induced nephropathy — View Citation

Persson PB, Hansell P, Liss P. Pathophysiology of contrast medium-induced nephropathy. Kidney Int. 2005 Jul;68(1):14-22. Review. — View Citation

Rihal CS, Textor SC, Grill DE, Berger PB, Ting HH, Best PJ, Singh M, Bell MR, Barsness GW, Mathew V, Garratt KN, Holmes DR Jr. Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention. Circulation. 2002 May 14;10 — View Citation

Section 4: Contrast-induced AKI. Kidney Int Suppl (2011). 2012 Mar;2(1):69-88. — View Citation

Thomsen HS. How to avoid CIN: guidelines from the European Society of Urogenital Radiology. Nephrol Dial Transplant. 2005 Feb;20 Suppl 1:i18-22. Review. — View Citation

Trivedi HS, Moore H, Nasr S, Aggarwal K, Agrawal A, Goel P, Hewett J. A randomized prospective trial to assess the role of saline hydration on the development of contrast nephrotoxicity. Nephron Clin Pract. 2003 Jan;93(1):C29-34. — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of contrast nephropathy during the first 48 hours after contrast administration	The incidence of contrast nephropathy, 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.	During the first 48 hours after contrast administration
Secondary	Determination of biomarkers of contrast nephropathy during the first 48 hours after contrast administration	To evaluate the clinical utility of different biomarkers for the early diagnosis of contrast nephropathy (cystatin C, MicroRNAs, NGAL, KIM-1, NAG, t-gelsolina, GM2AP, creatinine)	During the first 48 hours after contrast administration