Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Opioids in Chronic Kidney Disease Patients Undergoing Hemodialysis (OCKD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02452437
Recruitment Status : Unknown
Verified May 2015 by Emerio & Lourdes Linares Research and Education Center.
Recruitment status was:  Recruiting
First Posted : May 22, 2015
Last Update Posted : May 22, 2015
Sponsor:
Information provided by (Responsible Party):
Emerio & Lourdes Linares Research and Education Center

Tracking Information
First Submitted Date  ICMJE May 20, 2015
First Posted Date  ICMJE May 22, 2015
Last Update Posted Date May 22, 2015
Study Start Date  ICMJE May 2015
Estimated Primary Completion Date September 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 21, 2015)
Oxycodone's intradialytic mass transfer coefficient [ Time Frame: t=0 to t=4 hours ]
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Opioids in Chronic Kidney Disease Patients Undergoing Hemodialysis
Official Title  ICMJE Clinical Trial Simulation Using ODE/PDE Hemodialysis Model for Quantifying Oxycodone's Removal in End-Stage Kidney Disease
Brief Summary To measure oxycodone's intradialytic mass transfer rate coefficient and oxycodone's removal rate using an ODE/PDE hemodialysis model. To implement a rational clinical strategy for estimating a patient's post-hemodialysis oxycodone restoration dose using results from an ODE/PDE model of hemodialysis.
Detailed Description

Clinical Trial Simulation Design and Investigational Plan: Our study sample will consist of a group of 10 randomly selected virtual Caucasian hemodialysis patients with Stage 5 chronic kidney disease (CKD) and a group of 10 randomly selected Caucasian age and weight matched healthy controls. Patients, 5 women and 5 men in each group, will be synthesized using clinical trial simulation techniques from the case report data reported by Lee, Leng, and Cooper and the experiments by Kirvela and coworkers. Our goal is to learn about the populations from which the study samples are drawn. To meet this goal, the investigators will perform Monte Carlo simulation.

Both virtual control subjects and experimental hemodialysis patients meeting all inclusion/exclusion criteria will be studied in two phases.

In phase 1, subjects will receive a ceiling dose of controlled-release oxycodone hydrochloride (hereafter CR-OC) totaling 40 mg twice daily for 2 weeks prior to the experimental hemodialysis procedure on day 15. Because patients in the hemodialysis group will be anuric, they will undergo hemodialysis three times weekly.10 During that time, they will receive supplemental oral immediate-release oxycodone every 4 h as needed to control their pain up to a visual analog scale level of < 3. These pain levels would correspond with plasma oxycodone concentrations of 20-50 ng/mL.

Patients will be instructed to take their last dose of CR-OC 2 to 3 hours before starting the experimental hemodialysis procedure. This dosing schedule will ensure that the time to CR-OC's maximum concentration (Tmax) and its maximum concentration (Cmax) will be reached at the time of blood sampling at t = 0, enabling accurate assessment of CR-OC's elimination with negligible influence from absorption or redistribution.

At 8:00 am on the 15th day, and this is phase 2 of the study, each individual will undergo hemodialysis for 4 hours. Two independent simultaneous blood samples for measurement of plasma oxycodone concentrations from both arterial inflow (Cin) and venous outflow (Cout) sites will be obtained immediately upon starting hemodialysis (t = 0) and immediately after hemodialysis before shutting off the machine (t = 4). For all calculations and ODE/PDE modeling (see Model Diagram), the oxycodone concentrations from those samples will be combined and averaged. Oxycodone's intradialytic extraction ratio will be calculated from the simultaneously sampled arterial (inflow) and venous (outflow) plasma oxycodone concentrations by dividing their difference by the arterial plasma oxycodone concentrations.

Controls will eat three light meals and a bedtime snack daily. Hemodialysis patients will eat a standard renal diet. Foods will be free of known inhibitors of CYP2D6. Individuals will be digitally abstained from nicotine, caffeine, grapefruit juice and alcohol during the course of the study.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Chronic Kidney Disease
Intervention  ICMJE Drug: Oxycodone
Controlled release oxycodone 40 mg twice daily
Other Name: OxyContin
Study Arms  ICMJE
  • Experimental: control
    Oxycodone will be administered and subjects will undergo hemodialysis
    Intervention: Drug: Oxycodone
  • Experimental: hemodialysis
    Oxycodone will be administered and subjects will undergo hemodialysis
    Intervention: Drug: Oxycodone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: May 21, 2015)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2015
Estimated Primary Completion Date September 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Healthy, non-smoking, opioid intolerant Caucasian men and women controls.
  • Hemodialysis patients age 44 ± 10 (mean ± SD) years and normal controls 36 ± 9 years.
  • No statistically significant difference in weight between hemodialysis and control patients.
  • Mean serum creatinine concentrations of 7.29 ± 1.48 mg/dL in hemodialysis patients and 0.81 ± 0.12 mg/dL in controls (normal 0.7 to 1.3 mg/dL for men and 0.6 to 1.1 mg/dL for women)
  • Mean urine output of 1.83 ± 0.47 mL/hr (44 ± 11 mL/24 hr) in hemodialysis patients and 62.32 ± 16.01 mL/hr (1496 ± 384 mL/24 hr) in controls.
  • Patients in both groups with normal liver function. Serum prothrombin time (PT/INR), aPTT, albumin, bilirubin (direct and indirect), liver transaminases, gamma-glutamyl transferase and alkaline phosphatase normal.

Exclusion Criteria:

  • In both groups, a clinically significant electrocardiogram (ECG) abnormality.
  • An uncontrolled clinically significant cardiovascular condition other than end-stage kidney disease.
  • Elevated transaminases, alkaline phosphatase, bilirubin, low phosphodiesterase, elevated ammonia levels, low glucose, elevated lactate, elevated creatinine, and hypoxia (hepatorenal syndrome)
  • Serum positive for HIV, hepatitis BsAg, or Hepatitis C
  • A history of drug or alcohol abuse within the past 24 months
  • Currently participating (or participated within the previous 30 days in an investigational therapeutic or device study
  • Female who is pregnant, nursing, or of child-bearing potential not practicing effective contraceptive methods.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 30 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02452437
Other Study ID Numbers  ICMJE ELLHDM-001
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Emerio & Lourdes Linares Research and Education Center
Study Sponsor  ICMJE Emerio & Lourdes Linares Research and Education Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Oscar A Linares, MD Emerio & Lourdes Linares Research and Education Center
PRS Account Emerio & Lourdes Linares Research and Education Center
Verification Date May 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP