RenalGuard System and Contrast Media (REMEDIAL II)

This study is enrolling participants by invitation only.
Sponsor:
Information provided by:
Clinica Mediterranea
ClinicalTrials.gov Identifier:
NCT01098032
First received: April 1, 2010
Last updated: NA
Last verified: April 2010
History: No changes posted
  Purpose

The purpose of the present study is to assess the role of the RenalGuard System as compared to the optimal strategy (sodium bicarbonate infusion plus N-acetylcysteine (NAC)) in high and very-high risk patients to prevent contrast-induced acute kidney injury contrast induced acute kidney injury (CI-AKI).

Consecutive patients with chronic kidney disease, referred to our institutions for coronary and/or peripheral procedures, will be randomly assigned to 1) prophylactic administration of sodium bicarbonate plus NAC (Systemic alone therapy group; n = 100) and 2) RenalGuard System treatment (RenalGuard group; n= 100). All enrolled patients must have an estimated glomerular filtration rate <30 ml/min/1.73 m2 and/or a contrast nephropathy risk score ≥11). In all cases iodixanol (an iso-osmolar, non ionic contrast agent) will be administered. The primary end point is an increase of >=0.3 mg/dL in the creatinine concentration 48 hours after the procedure.

This study will give important answers on how to prevent CI-AKI in high and very-high risk patients undergoing contrast media exposure.


Condition Intervention Phase
Chronic Kidney Disease
Device: RenalGuard system
Drug: Sodium Bicarbonate and N-acetylcysteine
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: Renal Insufficiency Following Contrast Media Administration Trial II (Remedial II): The RenalGuard System in High-Risk Patients for Contrast-Induced Acute Kidney Injury

Resource links provided by NLM:


Further study details as provided by Clinica Mediterranea:

Primary Outcome Measures:
  • Rate of Contrast-induced acute kidney injury [ Time Frame: at 48 hours following contrast exposure ] [ Designated as safety issue: No ]
    The primary outcome measure will be development of CI-AKI, defined as an increase in the serum creatinine concentration >=0.3 mg/dL from the baseline value at 48 hours after administration of the contrast media or the need for dialysis.


Secondary Outcome Measures:
  • rate of kidney injury and major adverse events [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    1) an increase in the serum creatinine concentration >=0.25% and >=0.5 mg/dl at 48 hours after contrast exposure; 2) changes in the serum cystatin C concentration at 24 and 48 hours after contrast exposure, 3) changes in the urine and serum NGAL concentration after contrast exposure, 4) the rate of acute renal failure requiring dialysis, 4) the rate of in-hospital major adverse events (i.e. acute myocardial infarction, c) renal failure requiring dialysis, and d) acute pulmonary edema) and 5) the cost-effectiveness ratio.


Estimated Enrollment: 200
Study Start Date: January 2009
Estimated Study Completion Date: September 2010
Estimated Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Systemic alone therapy group
Systemic alone therapy grou will be treated by intravenous sodium bicarbonate plus NAC administration. Patients allocated to the Systemic alone therapy group will receive 154 mEq/l of sodium bicarbonate in dextrose and H2O, according to the protocol reported by Merten et al. (9) The initial intravenous bolus was 3 ml/kg per hour for 1 hour immediately before contrast injection. Following this, patients will receive the same fluid at a rate of 1 ml/kg per hour during contrast exposure and for 6 hours after the procedure. All patients will receive NAC (Fluimucil, Zambon Group SpA, Milan, Italy) orally at a dose of 1200 mg twice daily on the day before and on the day of administration of the contrast agent (total of 2 days. Additional NAC dose (1.2 g) will be administered i.v. during the procedure.
Drug: Sodium Bicarbonate and N-acetylcysteine
Patients allocated to the Systemic alone therapy group will receive 154 mEq/l of sodium bicarbonate in dextrose and H2O, according to the protocol reported by Merten et al. The initial intravenous bolus was 3 ml/kg per hour for 1 hour immediately before contrast injection. Following this, patients will receive the same fluid at a rate of 1 ml/kg per hour during contrast exposure and for 6 hours after the procedure. All patients will receive NAC (Fluimucil, Zambon Group SpA, Milan, Italy) orally at a dose of 1200 mg twice daily on the day before and on the day of administration of the contrast agent (total of 2 days)
Experimental: RenalGuard System group
Prophylactic controlled hydration with saline (0.9%) plus N-acetylcystein (NAC; 6 g in total). In the RenalGuard group, an initial bolus (priming) of 250 ml will be administered. In case of left ventricular dysfunction (ejection fraction ≤30%) and/or unstable hemodynamic conditions the bolus will be reduced to 150 ml. Following the initial bolus, furosemide (0.25 mg/kg) will be administered in order to achieve the optimal urine flow (≥300 ml/h). The hydration will be continued throughout the duration of the procedure and will last 4 hours following the procedure. Additional doses of furosemide are allowed in case of decrease of urine flow <300 ml/h.
Device: RenalGuard system
The RenalGuard™ System (PLC Medical Systems, Inc.) is a real-time measurement and real time matched fluid replacement device designed to accommodate the RenalGuard Therapy. The RenalGuard Therapy is based on the concept demonstrated by existing animal and clinical data that high urine output is beneficial to patients with impaired baseline renal function who receive intravascular iodinated contrast agents. The RenalGuard System seems to be ideal for the prevention of CI-AKI, by allowing an optimal urine flow rate >300 ml/h. It is known that excessive diuresis can cause dehydration which increases the risk to the kidneys from contrast media. The RenalGuard System should allow the patient to achieve high urine output safely by maintaining the intravascular blood volume. The RenalGuard System with its matched fluid replacement capability is intended to minimize the risk of over-or-under-hydration.

Detailed Description:

The strategy of volume supplementation by sodium bicarbonate plus N-acetylcysteine (NAC) seems to be the optimal pharmacological approach in preventing contrast induced acute kidney injury (CI-AKI) in patients at medium-to-high risk. Whether this prophylactic strategy is effective in high and very-high risk patients is unknown. In this subset of patients the potential protective effects and therapeutic advantage of a local delivery of protective compounds should be investigated. The RenalGuard™ System (PLC Medical Systes, Inc.) is a real-time measurement and real time matched fluid replacement device designed to accommodate the RenalGuard Therapy. The RenalGuard Therapy is based on the theory that creating and maintaining a high urine output is beneficial to patients undergoing imaging procedures where contrast agents are used. This should allow the body to rapidly eliminate contrast, reducing its toxic effects. The RenalGuard System seems to be ideal for the prevention of CI-AKI, by allowing an optimal urine flow rate >150 ml/h (ideally >300 ml/h). Preliminary data suggests that the RenalGuard System, by increasing the urine flow rate ≥ 300 ml/h, allows a quick renal first-pass elimination and therefore reduces the risk for contrast nephropathy. The potential benefits of RenalGuard Therapy are intended to reduce the incidence of CI-AKI via a combination of known physiological effects of high urine output including: a) lower concentration of contrast in the kidneys, b) more rapid transit of contrast through the kidneys, c) less overall exposure to toxic contrast, d) potential reduction of oxygen consumption in the medulla of the kidneys. No randomized study has been performed to assess the role of the RenalGuard System as compared to the optimal strategy (sodium bicarbonate infusion plus NAC) in high and very-high risk patients to prevent CI-AKI.

  Eligibility

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

Inclusion Criteria:

  1. Age >=18 years
  2. Chronic kidney disease (estimated glomerular filtration rate <=30 ml/min/1.72 m2) and/or
  3. Risk score for contrast nephropathy ≥11 (according to the Mehran score; J Am Coll Cardiol 2004; 44: 1393-1399)

Exclusion Criteria:

  1. Pregnancy
  2. Heart failure (NYHA functional class III-IV)
  3. Acute pulmonary edema
  4. Acute myocardial infarction
  5. Recent (<=2 days) contrast media exposure
  6. Patients enrolled in concomitant studies
  7. Administration of theophylline, dopamine, mannitol and fenoldopam.
  8. End-stage CKD (patients on chronic dialysis)
  9. Systemic hypotension (systolic blood pressure < 100 mg/dl).
  10. Multiple myeloma
  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: NCT01098032

Locations
Italy
Unversity of Ferrara, Department of Cardiology
Ferrara, Italy
IRCCS Multimedica
Milan, Italy
Unversity School of Medicine of Modena, Deparment of Cardiology
Modena, Italy
Clinica Mediterranea
Naples, Italy, 80121
Sponsors and Collaborators
Clinica Mediterranea
Investigators
Principal Investigator: Carlo Briguori, MD, PhD Clinica Mediterranea, Naples,. ITALY
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Carlo Briguori, MD, PhD, Clinica Mediterranea
ClinicalTrials.gov Identifier: NCT01098032     History of Changes
Other Study ID Numbers: NCTCM01
Study First Received: April 1, 2010
Last Updated: April 1, 2010
Health Authority: Italy: Ministry of Health

Keywords provided by Clinica Mediterranea:
Contrast media
Kidney
Complication

Additional relevant MeSH terms:
Kidney Diseases
Acute Kidney Injury
Renal Insufficiency
Renal Insufficiency, Chronic
Urologic Diseases
Acetylcysteine
N-monoacetylcystine
Contrast Media
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes
Diagnostic Uses of Chemicals

ClinicalTrials.gov processed this record on August 21, 2014