Deferiprone for the Prevention of Contrast-Induced Acute Kidney Injury

Study Overview
=================
Brief Summary
-----------------
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.

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.

Official Title
-----------------
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

Conditions
-----------------
Contrast-Induced Acute Kidney Injury

Intervention / Treatment
-----------------
* Drug: CRMD-001-Deferiprone
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18 or older eGFR of < 60 ml/min/1.73 m2 Presence of at least one additional risk factor: Diabetes Mellitus Age ≥ 75 years Left Ventricular Ejection Fraction ≤ 40% Exclusion Criteria: End-Stage Renal Disease Recent change in serum creatinine Primary PCI for STEMI Currently receiving mechanical ventilation Severe heart failure of cardiogenic shock Requirement for inotropic support (prior 30 days) Sustained hypertension > or = 200/110 Subject not expected to live for 90 days Anticipated use of ioxaglate or iohexol Currently receiving fenoldopam, dopamine, theophylline, aminophylline, mannitol, N-acetyl cysteine or Ascorbic acid Absolute neutrophil count < 1500 Hemoglobin < 8 gm/dL

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CRMD-001-Deferiprone<br> | Drug: CRMD-001-Deferiprone<br>* 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<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* 3 placebo tablets will be given every 12 hours for a total of 8 days, beginning 1-3 hours prior to angiography<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Acute Kidney Injury, Contrast-Induced Nephropathy, Labile Iron, Iron Chelation, Deferiprone