PROVOCATION Trial - PROphylactic intraVenOus Hydration for Contrast Agent Toxicity PreventION

This study has been completed.
Sponsor:
Collaborator:
Swiss National Science Foundation
Information provided by:
University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier:
NCT00130598
First received: August 12, 2005
Last updated: March 4, 2010
Last verified: March 2010
  Purpose

Contrast nephropathy (CN) remains a common complication of radiographic procedures and an important cause of hospital-acquired acute renal failure. Only hydration with saline is uniformly accepted and used in clinical practice as a cornerstone for the prevention of CN. But the optimal preventive strategy for CN is not known. Sodium bicarbonate might be even more effective than hydration with sodium chloride for prophylaxis of CN. Therefore the aim of the study is to evaluate the efficacy of two regimens of sodium bicarbonate compared with a prolonged infusion of sodium chloride in the prevention of CN.

Primary endpoint: Decrease in glomerular filtration rate (GFR) within 48 hours.


Condition Intervention Phase
Kidney Failure, Acute
Drug: NaCl 0.9% i.v. or NaBic 1.4% i.v. or NaBic 1.4% i.v. + NaBic p.o. (Nephrotrans®)
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: PROVOCATION Trial - PROphylactic intraVenOus Hydration for Contrast Agent Toxicity PreventION

Further study details as provided by University Hospital, Basel, Switzerland:

Primary Outcome Measures:
  • Decrease in glomerular filtration rate (GFR) within 48 hours. GFR is calculated using the abbreviated Modification of Diet in Renal Disease (MDRD) Study equation. [ Time Frame: 48 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Development of contrast nephropathy, defined as an increase >=25% in the baseline serum creatinine concentration within 48 hours [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
  • Development of contrast nephropathy, defined as an increase >=44umol/l in serum creatinine concentration within 48 hours [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
  • Development of contrast nephropathy, defined as an increase >=25% in the baseline serum cystatin C concentration or an increase >=0.35mg/l in serum cystatin C concentration within 48 hours [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
  • Postcontrast increase in serum cystatin C at day 1 and 2 [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
  • In-hospital morbidity (nonfatal myocardial infarction) and mortality [ Time Frame: 60 days ] [ Designated as safety issue: No ]
  • Dialysis dependency [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Length of stay [ Time Frame: 60 days ] [ Designated as safety issue: No ]
  • Total costs of hospitalization [ Time Frame: 60 days ] [ Designated as safety issue: No ]
  • 3-/12-month mortality [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • 3-/12-month hospitalization for cardiac causes [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • GFR at 3 and 12 months [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Enrollment: 258
Study Start Date: June 2005
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
control group: patients receive a preventive hydration with 154mEq/l saline at an ongoing rate of 1ml/kg per hour of at least 12 hours prior and after the procedure.
Drug: NaCl 0.9% i.v. or NaBic 1.4% i.v. or NaBic 1.4% i.v. + NaBic p.o. (Nephrotrans®)

control group: preventive hydration with 154mEq/l saline at 1ml/kg per hour of 12 hours prior and after the procedure.

7h-sodium bicarbonate: before contrast 3ml/kg NaHCO3 166mEq/l for one hour, followed by NaHCO3 166mEq/l (1ml/kg per hour until 6h after contrast).

short-term sodium bicarbonate: NaHCO3 166mEq/l (3ml/kg) as a bolus 20 minutes before contrast; ingestion of Nephrotrans® (500mg NaHCO3/capsule: 1 capsule/10kg) with 1-2 dl non-sparkling mineral water at the start of the infusion. Ingestion of non-sparkling mineral water in the first 6 hours after contrast.

Other Names:
  • NaCl 0.9% Braun®
  • NaBic 1.4% Bichsel®
  • Nephrotrans®
Active Comparator: 2
7h-sodium bicarbonate (according to the regimen used in a recently published study (slightly modified)14): before contrast a bolus of 3ml/kg NaHCO3 166mEq/l for one hour, followed by an infusion of NaHCO3 166mEq/l with a rate of 1ml/kg per hour until 6h after contrast.
Drug: NaCl 0.9% i.v. or NaBic 1.4% i.v. or NaBic 1.4% i.v. + NaBic p.o. (Nephrotrans®)

control group: preventive hydration with 154mEq/l saline at 1ml/kg per hour of 12 hours prior and after the procedure.

7h-sodium bicarbonate: before contrast 3ml/kg NaHCO3 166mEq/l for one hour, followed by NaHCO3 166mEq/l (1ml/kg per hour until 6h after contrast).

short-term sodium bicarbonate: NaHCO3 166mEq/l (3ml/kg) as a bolus 20 minutes before contrast; ingestion of Nephrotrans® (500mg NaHCO3/capsule: 1 capsule/10kg) with 1-2 dl non-sparkling mineral water at the start of the infusion. Ingestion of non-sparkling mineral water in the first 6 hours after contrast.

Other Names:
  • NaCl 0.9% Braun®
  • NaBic 1.4% Bichsel®
  • Nephrotrans®
Active Comparator: 3
short-term sodium bicarbonate: NaHCO3 166mEq/l (3ml/kg; patients with a body weight above 100kg 300ml) as a bolus 20 minutes before contrast; additionally ingestion of Nephrotrans® (500mg NaHCO3/capsule: 1 capsule/10kg) with 1-2 dl of San Pellegrino® non-sparkling mineral water at the start of the infusion. Ingestion of 500ml San Pellegrino® non-sparkling mineral water in the first 6 hours after contrast.
Drug: NaCl 0.9% i.v. or NaBic 1.4% i.v. or NaBic 1.4% i.v. + NaBic p.o. (Nephrotrans®)

control group: preventive hydration with 154mEq/l saline at 1ml/kg per hour of 12 hours prior and after the procedure.

7h-sodium bicarbonate: before contrast 3ml/kg NaHCO3 166mEq/l for one hour, followed by NaHCO3 166mEq/l (1ml/kg per hour until 6h after contrast).

short-term sodium bicarbonate: NaHCO3 166mEq/l (3ml/kg) as a bolus 20 minutes before contrast; ingestion of Nephrotrans® (500mg NaHCO3/capsule: 1 capsule/10kg) with 1-2 dl non-sparkling mineral water at the start of the infusion. Ingestion of non-sparkling mineral water in the first 6 hours after contrast.

Other Names:
  • NaCl 0.9% Braun®
  • NaBic 1.4% Bichsel®
  • Nephrotrans®

  Hide Detailed Description

Detailed Description:

Background: Contrast nephropathy (CN) remains a common complication of radiographic procedures and an important cause of hospital-acquired acute renal failure, which contributes to morbidity and mortality during hospitalization, as well as costs of health care. Many previous strategies to prevent CN (such as N-acetylcysteine, aminophylline, fenoldopam, hemofiltration) have been unsuccessful or at least controversial. Only hydration with saline is uniformly accepted and used in clinical practice as cornerstone for the prevention of CN. But the optimal preventive strategy for CN is not known. According to a recent study, periprocedural hydration with sodium bicarbonate might be even more effective than hydration with sodium chloride for prophylaxis of CN. Such a preventive hydration with sodium bicarbonate should be compared with the gold standard of hydration with saline (24-h hydration period). This has not been evaluated so far. Given its high oral bioavailability, sodium bicarbonate could be administered even orally instead of a prolonged infusion. An effective short-term regimen would be highly attractive in clinical practice including outpatient procedures.

Aim: To evaluate the efficacy of two regimens of sodium bicarbonate compared with a prolonged infusion of sodium chloride in the prevention of CN.

Primary endpoint: Decrease in glomerular filtration rate (GFR) within 48 hours. GFR is calculated using the abbreviated Modification of Diet in Renal Disease Study equation. Secondary endpoints: Development of contrast nephropathy defined by increase in serum creatinine concentration of at least 44umol/l within 48 hours, an increase >=25% in the baseline serum creatinine concentration within 48 hours, or defined as an increase >=25% in the baseline serum cystatin C concentration or an increase >=0.35mg/l in serum cystatin C concentration within 48 hours; increase in serum cystatin C level at day 1 and 2, in-hospital morbidity (nonfatal myocardial infarction) and mortality, dialysis, length of stay, total costs of hospitalization, 3-/12-month mortality, 3-/12-month hospitalization for cardiac causes, and GFR at 3 and 12 months.

Patients and Methods: This randomized, controlled open-label trial is designed to enroll 258 patients at increased risk for CN because of renal dysfunction undergoing intraarterial or intravenous radiographic contrast procedures. Patients will be randomly assigned 1:1:1 with the use of sealed envelopes into 3 groups (block randomisation for intraarterial and intravenous radiographic contrast procedures) :

  1. a control group: patients receive a preventive hydration with 154mEq/l saline at an ongoing rate of 1ml/kg per hour of at least 12 hours prior and after the procedure.
  2. a group with 7h-sodium bicarbonate (according to the regimen used in a recently published study (slightly modified)14): before contrast a bolus of 3ml/kg NaHCO3 166mEq/l for one hour, followed by an infusion of NaHCO3 166mEq/l with a rate of 1ml/kg per hour until 6h after contrast.
  3. a group with short-term sodium bicarbonate: NaHCO3 166mEq/l (3ml/kg; patients with a body weight above 100kg 300ml) as a bolus 20 minutes before contrast; additionally ingestion of Nephrotrans® (500mg NaHCO3/capsule: 1 capsule/10kg) with 1-2 dl of San Pellegrino® non-sparkling mineral water at the start of the infusion. Ingestion of 500ml San Pellegrino® non-sparkling mineral water in the first 6 hours after contrast.

Expected results: It is the researchers' hypothesis that a short-term periprocedural preventive hydration with sodium bicarbonate will be non-inferior to the regimen of long-term hydration with sodium bicarbonate. The long-term regimen with sodium bicarbonate is expected to be superior to the standard i.v. regimen with sodium chloride.

Significance: Given the significant morbidity and mortality associated with acute renal failure due to contrast media as well as the widespread use of contrast media in an ambulant setting for diagnostic and therapeutical procedures, preventive short-term hydration with sodium bicarbonate could represent a major advance in clinical medicine.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • All patients admitted with renal dysfunction (baseline serum creatinine level above the upper limit of normal of the serum creatinine [>93umol/l for women and >117umol/l for men] or GFR <60ml/min [GFR calculated using the abbreviated MDRD study equation]) scheduled to undergo an intraarterial or intravenous radiographic contrast procedure within the next 24 hours.

Exclusion Criteria:

  • Age <18 years
  • Preexisting dialysis
  • Allergy to radiographic contrast
  • Pregnancy (women < 50 years: pregnancy test required)
  • Severe heart failure (New York Heart Association [NYHA] III-IV)
  • N-acetylcysteine </= 24 hours before contrast
  • Clinically vulnerable condition requiring continuous fluid therapy e.g. severe sepsis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00130598

Locations
Italy
Centro Cardiologico Monzino
Milano, Italy, 20138
Switzerland
University Hospital of Basel
Basel, Switzerland, 4031
Kantonsspital Liestal - Universitätskliniken
Liestal, Switzerland, 4100
Sponsors and Collaborators
University Hospital, Basel, Switzerland
Swiss National Science Foundation
Investigators
Principal Investigator: Christian Mueller, Prof. University Hospital of Basel
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University Hospital, Basel, Switzerland, Christian Mueller, MD
ClinicalTrials.gov Identifier: NCT00130598     History of Changes
Other Study ID Numbers: PROVOCATION Trial, 23.05, 05.013, 2005DR3170
Study First Received: August 12, 2005
Last Updated: March 4, 2010
Health Authority: Switzerland: Swissmedic

Keywords provided by University Hospital, Basel, Switzerland:
contrast nephropathy
contrast media
renal dysfunction

Additional relevant MeSH terms:
Renal Insufficiency
Acute Kidney Injury
Kidney Diseases
Urologic Diseases
Contrast Media
Diagnostic Uses of Chemicals
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014