- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00683553
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)
A Phase I, Randomized, Double-Blind, Dose Escalation Trial of the Safety and Pharmacokinetics of a Single Intravenous Injection of I5NP in Patients at High Risk of Acute Kidney Injury Undergoing Major Cardiovascular Surgery
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 risk for AKI (CCF score ≥ 5 OR an estimated GFR (eGFR) <60 mL/min/1.73 m2) who have undergone major cardiovascular surgery will participate. Patients will receive a single IV injection of I5NP or placebo following cardiovascular surgery. I5NP will be administered 4 hours (+/- 30 minutes) following removal of the cardiopulmonary bypass machine (CBM).
The duration of the study is approximately 44 days, inclusive of a 14 day screening period. Patients will be contacted by phone at 6 and 12 months for follow-up questions. Patient visits are screening, day of surgery, hospital in-patient Days 1, 2, 3 - 5 and Day 7 or hospital discharge. Safety follow-up will continue until 30 days post-surgery. 2 phone calls will be made at 6 and 12 months after date of surgery.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Alabama
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Birmingham, Alabama, United States, 35233
- University of Alabama at Birmingham
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Arizona
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Phoenix, Arizona, United States, 85054
- Mayo Clinic Hospital
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District of Columbia
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Washington, District of Columbia, United States, 20037
- George Washington University
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Missouri
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St. Louis, Missouri, United States, 63110
- Washington University
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Ohio
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Cleveland, Ohio, United States, 44195
- Cleveland Clinic Foundation
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15213
- University of Pittsburgh Medical Center
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Texas
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Houston, Texas, United States, 77030
- The Methodist Hospital
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Houston, Texas, United States, 77030
- University of Texas
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Houston, Texas, United States, 77030
- Texas Heart Institute
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Virginia
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Charlottesville, Virginia, United States, 22908-0688
- University of Virginia School of Medicine
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: PREVENTION
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: TRIPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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PLACEBO_COMPARATOR: Placebo
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Single IV injection of experimental drug given in escalated doses at 0.5, 1.5, 5.0 and 10 mg/kg doses to different patients
Other Names:
Single IV injection of saline
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EXPERIMENTAL: I5NP drug
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Single IV injection of experimental drug given in escalated doses at 0.5, 1.5, 5.0 and 10 mg/kg doses to different patients
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Number of Dose Limiting Toxicities (DLTs) observed among 4 cohorts of 6-12 patients per cohort
Time Frame: Reviewed at the conclusion of each cohort
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Reviewed at the conclusion of each cohort
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Pharmacokinetics
Time Frame: Immediately following injection through 24 hrs
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Immediately following injection through 24 hrs
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- QRK.004
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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