Deferiprone for the Prevention of Contrast-Induced Acute Kidney Injury

A Phase II, Randomized, Double-Blind, Placebo-Controlled Trial to Assess the Efficacy and Safety of CRMD-001 in Contrast-Induced Acute Oxidative Kidney Injury

The primary objective of this trial is to assess the impact of CRMD-001 on markers of contrast-induced acute kidney injury (AKI) in high-risk patients with chronic kidney disease (CKD) undergoing coronary angiography and PCI.

Study Overview

• Status: Completed
• Conditions: Contrast-Induced Acute Kidney Injury
• Intervention / Treatment: Drug: CRMD-001-Deferiprone; Drug: Placebo

Detailed Description

This trial will evaluate whether treatment with CRMD-001 (unique formulations of the iron chelator, Deferiprone) will reduce the incidence of AKI in subjects with CKD and additional risk factors. Adult subjects with moderate to severe CKD who are undergoing coronary angiography and PCI will be randomized to either placebo or CRMD-001 and followed for 90 days. Subjects will receive 8 days of randomized therapy starting 1-3 hours prior to angiography. The primary endpoint of the trial will be the difference in mean paired change of a panel of sensitive renal biomarkers between the groups. Differences in renal or cardiovascular clinical events will also be evaluated.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46290
      • The Care Group, St. Vincent's Hospital
  • Michigan
    • Detroit, Michigan, United States, 48236
      • St. John Hospital and Medical Center
    • Petoskey, Michigan, United States, 49770
      • Cardiac and Vascular Research Center of Northern Michigan
    • Southfield, Michigan, United States, 48075
      • Providence Hospital
  • Ohio
    • Columbus, Ohio, United States, 43214
      • Ohio Health Research Institute
    • Fairfield, Ohio, United States, 45104
      • Cardiovascular Catheterization Labs at Fairfield
    • Toledo, Ohio, United States, 43608
      • St. Vincent Mercy Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Oklahoma Cardiovascular Research Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18 or older
2. eGFR of < 60 ml/min/1.73 m2

3. Presence of at least one additional risk factor:

   • Diabetes Mellitus
   • Age ≥ 75 years
   • Left Ventricular Ejection Fraction ≤ 40%

Exclusion Criteria:

1. End-Stage Renal Disease
2. Recent change in serum creatinine
3. Primary PCI for STEMI
4. Currently receiving mechanical ventilation
5. Severe heart failure of cardiogenic shock
6. Requirement for inotropic support (prior 30 days)
7. Sustained hypertension > or = 200/110
8. Subject not expected to live for 90 days
9. Anticipated use of ioxaglate or iohexol
10. Currently receiving fenoldopam, dopamine, theophylline, aminophylline, mannitol, N-acetyl cysteine or Ascorbic acid
11. Absolute neutrophil count < 1500
12. Hemoglobin < 8 gm/dL

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; 3 placebo tablets will be given every 12 hours for a total of 8 days, beginning 1-3 hours prior to angiography
EXPERIMENTAL: CRMD-001-Deferiprone	Drug: CRMD-001-Deferiprone; CRMD-001 represents unique formulations of Deferiprone. Subjects will be given one (900 mg) immediate release and two (900 mg) extended release tablets 1-3 hours prior to angiography and then every 12 hours for a total of 8 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarker evidence of Acute Kidney injury	Mean paired change in a panel of acute kidney injury (AKI) biomarkers (urinary NGAL, LFABP, interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), urinary alpha GST (proximal tubular injury), Pi GST (distal tubular injury) and cystatin C; serum cystatin C) from baseline (Day 1) to peak in the deferiprone and placebo treatment groups, within 192 hours of contrast exposure	8 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Acute Kidney Injury	Incidence of AKI defined as an absolute increase in serum Cr of ≥ 0.3 mg/dL, and/or a 50% relative increase in serum Cr from baseline (Day 1) to a maximum value obtained within 48 hours of contrast exposure	48 hours

Collaborators and Investigators

• Sponsor: CorMedix
• Investigators: Principal Investigator: Peter A. McCullough, MD, MPH, St. John Providence Health System, Novi, MI

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (ACTUAL): June 1, 2011
• Study Completion (ACTUAL): June 1, 2011

Study Registration Dates

• First Submitted: June 16, 2010
• First Submitted That Met QC Criteria: June 16, 2010
• First Posted (ESTIMATE): June 22, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): June 27, 2011
• Last Update Submitted That Met QC Criteria: June 23, 2011
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Keywords: Acute Kidney Injury; Deferiprone; Iron Chelation; Contrast-Induced Nephropathy; Labile Iron
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Wounds and Injuries; Acute Kidney Injury; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Iron Chelating Agents; Deferiprone
• Other Study ID Numbers: CRMD-001-2001