Status:

TERMINATED

A Dose Escalation and Safety Study of I5NP to Prevent Acute Kidney Injury (AKI) in Patients at High Risk of AKI Undergoing Major Cardiovascular Surgery (QRK.004)

Lead Sponsor:

Quark Pharmaceuticals

Conditions:

Acute Renal Failure

Acute Kidney Injury

Eligibility:

All Genders

21-85 years

Phase:

PHASE1

Brief Summary

This is a Phase 1, randomized, double-blind, dose escalation, safety and pharmacokinetic study. The study will be conducted in approximately 10 sites in the United States. Up to 48 patients at high ri...

Detailed Description

The drug (I5NP) is a small interfering RNA that is being developed to protect patients from acute kidney injury after cardiac bypass surgery. This study will test the safety of I5NP and measure how lo...

Eligibility Criteria

Inclusion

  • Inclusion Criteria (before surgery):
  • Patient age between 21 years and 85 years old
  • Patient is capable of giving consent
  • Patient is willing and able to comply with the visit schedule and study procedures including post-hospitalization discharge follow-up
  • Patient is undergoing any major cardiac or vascular surgery requiring the use of cardiopulmonary bypass machine (CBM)
  • Patient has a cumulative score of ≥ 5 on the Cleveland Clinic Foundation (CCF) Acute Kidney Injury (AKI) risk factor scale OR the patient has an estimated GFR (eGFR) \<60 mL/min/1.73 m2, as determined from the simplified (4-variable) MDRD (Modification of Diet in Renal Disease) equation at the time of the Screening/Baseline examination
  • The patient reports that they are up to date and have had normal findings on their age- and sex-appropriate cancer screening, per American Cancer Society guidelines, for breast cancer, cervical cancer, rectal cancer, and prostate cancer. If a patient is not up to date, the relevant screening test must be performed and a normal result documented prior to dosing.
  • Inclusion Criteria (during surgery):
  • Patient must have been on cardiopulmonary bypass machine (CBM)
  • Inclusion Criteria (after surgery):
  • Patient must be in the ICU for dosing to facilitate study procedures including PK blood draws and PK urine sampling
  • Exclusion Criteria (before surgery):
  • Patient has had cancer or may be predisposed due to a family history of:
  • a clinical syndrome predisposing to malignancy, such as Familial Polyposis Coli, Von Hippel Landau disease (associated with renal cell cancers and renal cysts) and Li-Fraumeni syndrome (associated with inherited mutations of the p53 tumor-suppressor gene)
  • the same malignancy in two or more first- or second-degree relatives
  • Patient has a history of any abnormality on chest X-ray that could represent a malignancy
  • Patient has a clinically significantly elevated pancreatic and/or hepatic enzyme level, defined as any grade 2, 3 or 4 value according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), version 3.0
  • Women of childbearing potential are to be excluded from this study. Every female subject is considered of childbearing potential unless she has had sterilization surgery, or is post-menopausal.
  • Women 21-59, post-menopausal is defined as no menses for at least 12 months and an elevated follicle stimulating hormone (FSH) level.
  • Women 60-85, post-menopausal is defined as no menses in at least 12 months.
  • Patient has participated in a study of an experimental therapy in the last 30 days
  • Patient is currently receiving immunosuppressive therapy \[this criterion does NOT apply to topical steroids and inhalation steroids for chronic obstructive pulmonary disease (COPD) and/or asthma\]
  • Pre-operative extracorporeal membrane oxygenation
  • Patient has Intra-Arterial Balloon Pump (IABP) or other Left Ventricular Assist Device (LVAD)
  • Evidence that patient is experiencing possible AKI prior to surgery, defined as a \> 1.5 times increase in serum creatinine from screening to any time prior to surgery
  • Patient has comfort measures only or do not resuscitate (DNR) status
  • Patient is participating in a concurrent interventional study
  • Patient has received intravenous contrast material \< 24 hours prior to surgery
  • In the opinion of the investigator a pre-operative concomitant disease or clinical/laboratory finding that significantly raises the risk of complications in the post-operative period and therefore precludes dosing of the patient
  • Exclusion Criteria (during surgery):
  • In the opinion of the investigator, an intra-operative complication has occurred that significantly raises the risk of complications in the post operative period and therefore precludes dosing of the patient
  • Exclusion Criteria (after surgery):
  • In the opinion of the investigator, a complication has occurred in the post-operative period at any time prior to dosing that significantly raises the risk of further complications and therefore precludes dosing of the patient

Exclusion

    Key Trial Info

    Start Date :

    May 1 2008

    Trial Type :

    INTERVENTIONAL

    Allocation :

    ACTUAL

    End Date :

    September 1 2010

    Estimated Enrollment :

    3 Patients enrolled

    Trial Details

    Trial ID

    NCT00683553

    Start Date

    May 1 2008

    End Date

    September 1 2010

    Last Update

    November 16 2010

    Active Locations (10)

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    Page 1 of 3 (10 locations)

    1

    University of Alabama at Birmingham

    Birmingham, Alabama, United States, 35233

    2

    Mayo Clinic Hospital

    Phoenix, Arizona, United States, 85054

    3

    George Washington University

    Washington D.C., District of Columbia, United States, 20037

    4

    Washington University

    St Louis, Missouri, United States, 63110

    A Dose Escalation and Safety Study of I5NP to Prevent Acute Kidney Injury (AKI) in Patients at High Risk of AKI Undergoing Major Cardiovascular Surgery (QRK.004) | DecenTrialz