Single Dose rATG for Renal Allograft Rejection

Single Dose rATG for Treatment of Acute Renal Allograft Rejection

Rabbit antithymocyte globulin (rATG) is approved for the treatment of acute rejection following kidney transplantation and is routinely administered as a series of 5-7 consecutive daily doses via central intravenous catheter.Single large-doses of rATG have been shown to have equivalent safety and efficacy profile compared to the standard daily protocol when used as an induction agent but there are no reported experiences of its use for rejection treatment. Plan to study a single-dose rATG infusion compared to standard rATG administration including correlation to length of hospital stay and hospital costs.

Study Overview

• Status: Unknown
• Conditions: Acute (Cellular) Renal Allograft Rejection
• Intervention / Treatment: Drug: rATG

Detailed Description

Rabbit antithymocyte globulin (rATG) is approved for the treatment of acute rejection following kidney transplantation and is routinely administered as a series of 5-7 consecutive daily doses via central intravenous catheter. This prolonged course is not consistent with the Medicare diagnosis-related group (DRG) for acute rejection which limits rejection admission to 3 days. The prolonged hospitalization results in increased medical costs and uniform financial loss to the hospital for patients admitted under this DRG. In addition there is a patient related toll of the prolonged hospitalization and a potential for additional hospital acquired complications. Single large-doses of rATG have been shown to have equivalent safety and efficacy profile compared to the standard daily protocol when used as an induction agent but there are no reported experiences of its use for rejection treatment. The investigators hypothesize that single-dose rATG infusion will be as safe and efficacious as standard rATG administration when used for rejection treatment and would result in significant reduction in the length of hospital stay (LOS) and hospital costs for rejection treatment.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Houston Methodist Hospital
      • Contact: Darrel W Cleere, RN, CCRC; Phone Number: 713-441-6232; Email: dwcleere@houstonmethodist.org
      • Principal Investigator: Samir J Patel, Pharm.D.
      • Sub-Investigator: Richard J Knight, MD
      • Sub-Investigator: Jill Krisl, Pharm.D.
      • Sub-Investigator: A. Osama Gaber, MD
      • Sub-Investigator: Samantha A Kuten, Pharm.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female subjects aged 18 years or older

2. Experiencing a biopsy-proven acute rejection episode which:

   • will require the use of rATG based on severity, or
   • is exhibiting resistance to corticosteroid treatment, defined as failure of the serum creatinine to decrease after at least 3 days of corticosteroid treatment (≥200 mg/day of methylprednisolone or equivalent)

Exclusion Criteria:

1. Patients with known severe allergy to antithymocyte globulin or rabbits
2. Rejection episode requiring the use of therapeutic plasma exchange immediately subsequent to rATG administration
3. Currently receiving any investigational drug or treatments

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Standard dose rATG; Standard dose rATG given as daily infusions of 1.5 mg/kg x 4-5 days	Drug: rATG; Infusion of horse or rabbit-derived antibodies against human T cells, used to prevent & treat acute rejection in organ transplantation; Other Names: ATG; Thymoglobulin; Rabbit antithymocyte globulin
EXPERIMENTAL: Single dose rATG; Single dose rATG give as 2 consecutive 3 mg/kg IV infusions to be completed over a 24-36 hour duration	Drug: rATG; Infusion of horse or rabbit-derived antibodies against human T cells, used to prevent & treat acute rejection in organ transplantation; Other Names: ATG; Thymoglobulin; Rabbit antithymocyte globulin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital length of hospitalization (days)	The length of hospitalization for treatment of renal allograft rejection in days will be determined which should be an average of 5-7 days	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infusion related symptoms	Incidence of grade 1, 2, or 3 infusion-related symptoms, graded according to common terminology criteria will be determined during the patient's hospital admission, which should be an average of 5-7 days	7 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of 30-day readmissions (%)	Proportion of participants re-admitted to the hospital from discharge to day 30 for each group	30 days
Incidence of leukopenia	Incidence leukopenia, graded according the to common terminology criteria	6 months
Incidence of neutropenia (%)	Incidence of neutropenia, graded according the to common terminology criteria	6 months
Incidence of thrombocytopenia (%)	Incidence of thrombocytopenia, graded according the to common terminology criteria	6 months
Incidence of BK viremia (%)	Incidence of BK viremia or nephropathy at 6 months	6 months
Incidence of cytomegalovirus (CMV) viremia (%)	Incidence of CMV viremia or disease at 6 months	6 months
Non-hematologic adverse events (%)	Non-hematologic adverse events (i.e. serum sickness)	6 months
Clinical reversal of rejection	Clinical reversal of rejection, defined as the return of serum creatinine to pre-rejection creatinine	6 months
Time to reversal of rejection	Number of days to reversal of rejection	6 months
Histological reversal of rejection	Biopsy demonstrated absence of rejection if available	6 months
Kidney function status at 1, 3 and 6 months post-rejection treatment	Serum creatinine at 1, 3 and 6 months post-rejection treatment	6 months

Collaborators and Investigators

• Sponsor: The Methodist Hospital Research Institute
• Investigators: Principal Investigator: Samir Patel, PharmD, The Methodist Hospital Research Institute

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (ANTICIPATED): March 1, 2021
• Study Completion (ANTICIPATED): October 1, 2021

Study Registration Dates

• First Submitted: March 26, 2014
• First Submitted That Met QC Criteria: April 2, 2014
• First Posted (ESTIMATE): April 3, 2014

Study Record Updates

• Last Update Posted (ACTUAL): September 3, 2020
• Last Update Submitted That Met QC Criteria: September 1, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: kidney transplantation; acute rejection; rabbit antithymocyte globulin
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Thymoglobulin; Antilymphocyte Serum
• Other Study ID Numbers: Pro00003442; 0809-0111 (OTHER: HMRI IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No