Prospective Pilot Study of Pre-Transplant Thymoglobulin Administration in Living Donor Renal Transplant Recipients

• Sponsor: University of Cincinnati (Other)
• Overall Status: Completed
• CT.gov ID: NCT00771745
• Collaborator: Genzyme, a Sanofi Company (Industry)
• Enrollment: 11
• Location: 1
• Arms: 2
• Duration (Months): 21.9
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

To determine how safe and effective giving Thymoglobulin before transplantation to patients who are going to be receiving kidney transplants.

Condition or Disease	Intervention/Treatment	Phase
Renal Transplant Rejection; Transplants and Implants	Drug: Thymoglobulin; Drug: Thymoglobulin	Phase 4

Detailed Description

We will evaluate the therapeutic efficacy of administering Thymoglobulin® induction pre-transplantation in renal allograft recipients. Patients receiving pre-transplant Thymoglobulin will be evaluated for acute rejection (Banff '97 criteria), survival, and safety at 6 months. Overall the use of Thymoglobulin induction pre-transplantation will be safe and effective.

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Prospective, Single Center, Pilot Study of Pretransplant Thymoglobulin Administration and Early Corticosteroid Withdrawal in Living Donor Renal Transplant Recipients Under Mycophenolate Mofetil (MMF) and Tacrolimus Immunosuppression
• Study Start Date: Sep 1, 2008
• Actual Primary Completion Date: Jun 1, 2010
• Actual Study Completion Date: Jul 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: rATG 4 doses Preloading Induction with Thymoglobulin® X 4 doses given day -4, day -2, day 0, and day 2 at 1.5 mg/kg/dose + corticosteroid taper + tacrolimus + MMF	Drug: Thymoglobulin; Preloading Induction with Thymoglobulin® X 4 doses given day -4, day -2, day 0, and day 2 at 1.5 mg/kg/dose + corticosteroid taper + tacrolimus + MMF; Other Names: Anti-thymocyte globulin (rabbit), thymoglobulin rATG
Active Comparator: rATG 3 doses Preloading Induction with Thymoglobulin® X 3 doses given day -4 (1.5mg/kg), day -2 (1.5mg/kg), and day 0 (3mg/kg) + corticosteroid taper + tacrolimus + MMF	Drug: Thymoglobulin; Preloading Induction with Thymoglobulin® X 3 doses given day -4 (1.5mg/kg), day -2 (1.5mg/kg), and day 0 (3mg/kg) + corticosteroid taper + tacrolimus + MMF; Other Names: anti-thymocyte globulin (rabbit), thymoglobulin rATG

Outcome Measures

Primary Outcome Measures

1. Composite End Point of Acute Rejection, Graft Loss or Patient Death [6 months]

   Proportion of Patients Meeting the Composite End Point of Acute Rejection, Graft loss or Patient death

Secondary Outcome Measures

1. Incidence of Treatment Failures: Defined as the Percentage of Patients That do Not Remain on Initial Therapy. [Ongoing]

2. Incidence of Infections [Not defined]

3. Need for Antilymphocyte Antibody Therapy to Treat Acute Rejection [Not defined]

4. Severity of Biopsy-proven Rejection Using Banff 97 Criteria [Not defined]

5. Serum Creatinine [Post-operative days 1-7, 30, 90 and 6 months]

6. Malignancy [Undefined]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Adult living donor renal transplant recipient.

2. Patient is at least 18 years of age

3. If female and of childbearing potential, have a negative serum or urine HCG within 24 hours prior to Study Day -5 (Day of 1st Thymoglobulin dose) and must practice a medically approved method of birth control for the past 30 days prior to enrollment and agree to continue this practice during the 6 month efficacy analysis.

4. Signed informed consent.

Exclusion Criteria:

1. Human Leukocyte Antibody (HLA) identical living donor transplant recipient.

2. History of a positive cross-match with the donor.

3. Patients with a peak CDC PRA > 50% or a current CDC PRA > 25%.

4. Patients who have previously received a kidney transplant.

5. Active donor or recipient serology positive for human immunodeficiency virus (HIV), Hepatitis B virus (HBV), or Hepatitis C virus (HCV).

6. History of noncompliance.

7. History of chronic corticosteroid or immunosuppressive use except for inhaled corticosteroids to treat asthma. .

8. Multiple organ transplant recipient.

9. Patient with a urinary bladder that is absent or not functional (e.g. self catheterization) pretransplant.

10. Patient who does not agree to use effective birth control during the 6-month efficacy analysis.

11. Known contraindication to administration of rabbit antithymocyte globulin.

12. Initial screening laboratory evaluations will be done locally before renal transplantation and the following laboratory values will be exclusionary: Platelets < 100,000/mm23 or WBC < 3000/mm3

13. Currently abusing drugs or alcohol or, in the opinion of the investigator, is at high risk for poor compliance.

14. Patient who, in the opinion of the investigator, has significant medical or psychosocial problems or unstable disease states that would preclude participation in the study. Examples of significant problems include, but are not limited to, morbid obesity or severe cardiac disease.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Christ Hospital	Cincinnati	Ohio	United States	45219

Sponsors and Collaborators

• University of Cincinnati
• Genzyme, a Sanofi Company

Investigators

• Principal Investigator: E. Steve Woodle, MD, University of Cincinnati
• Principal Investigator: Adele Rike, PharmD, The Christ Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: E. Steve Woodle, MD, FACS, University of Cincinnati
• ClinicalTrials.gov Identifier: NCT00771745
• Other Study ID Numbers: Pre-Tx Thymo
• First Posted: Oct 13, 2008
• Last Update Posted: Jan 18, 2016
• Last Verified: Dec 1, 2015

• Additional relevant MeSH terms: Thymoglobulin; Antilymphocyte Serum

Study Results

Participant Flow

Arm/Group Title	Preloading Induction With Thymoglobulin	Preloading Induction With Thymoglobulin® X 3 Doses
Arm/Group Description	Preloading Induction with Thymoglobulin® X 4 doses given day -4, day -2, day 0, and day 2 at 1.5 mg/kg/dose + corticosteroid taper + tacrolimus + MMF anti-thymocyte globulin (rabbit) : Preloading Induction with Thymoglobulin® X 4 doses given day -4, day -2, day 0, and day 2 at 1.5 mg/kg/dose + corticosteroid taper + tacrolimus + MMF	Preloading Induction with Thymoglobulin® X 3 doses given day -4 (1.5mg/kg), day -2 (1.5mg/kg), and day 0 (3mg/kg) + corticosteroid taper + tacrolimus + MMF anti-thymocyte globulin (rabbit) : Preloading Induction with Thymoglobulin® X 3 doses given day -4 (1.5mg/kg), day -2 (1.5mg/kg), and day 0 (3mg/kg) + corticosteroid taper + tacrolimus + MMF
Period Title: Overall Study
STARTED	6	5
COMPLETED	6	5
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Preloading Induction With Thymoglobulin	Preloading Induction With Thymoglobulin® X 3 Doses	Total
Arm/Group Description	Preloading Induction with Thymoglobulin® X 4 doses given day -4, day -2, day 0, and day 2 at 1.5 mg/kg/dose + corticosteroid taper + tacrolimus + MMF anti-thymocyte globulin (rabbit) : Preloading Induction with Thymoglobulin® X 4 doses given day -4, day -2, day 0, and day 2 at 1.5 mg/kg/dose + corticosteroid taper + tacrolimus + MMF	Preloading Induction with Thymoglobulin® X 3 doses given day -4 (1.5mg/kg), day -2 (1.5mg/kg), and day 0 (3mg/kg) + corticosteroid taper + tacrolimus + MMF anti-thymocyte globulin (rabbit) : Preloading Induction with Thymoglobulin® X 3 doses given day -4 (1.5mg/kg), day -2 (1.5mg/kg), and day 0 (3mg/kg) + corticosteroid taper + tacrolimus + MMF	Total of all reporting groups
Overall Participants	6	5	11
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	6 100%	5 100%	11 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.1 (17.1)	36.1 (12.5)	43.1 (17.1)
Sex: Female, Male (Count of Participants)
Female	1 16.7%	2 40%	3 27.3%
Male	5 83.3%	3 60%	8 72.7%
Region of Enrollment (participants) [Number]
United States	6 100%	5 100%	11 100%

Outcome Measures

1. Primary Outcome

Title	Composite End Point of Acute Rejection, Graft Loss or Patient Death
Description	Proportion of Patients Meeting the Composite End Point of Acute Rejection, Graft loss or Patient death
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Patients received tacrolimus (goal level 10-15 ng/mL) and mycophenolate mofetil (2gm daily) at time of transplant. Methylprednisolone (MP), acetaminophen, and diphenhydramine were given as premedication for each rATG dose (500mg MP 1st dose, 250mg MP subsequent 2 doses, 125mg MP 4th dose).

Arm/Group Title	Preloading Induction With Thymoglobulin x 4 Doses	Preloading Induction With Thymoglobulin® X 3 Doses
Arm/Group Description	Preloading Induction with Thymoglobulin® X 4 doses given day -4, day -2, day 0, and day 2 at 1.5 mg/kg/dose + corticosteroid taper + tacrolimus + MMF anti-thymocyte globulin (rabbit) : Preloading Induction with Thymoglobulin® X 4 doses given day -4, day -2, day 0, and day 2 at 1.5 mg/kg/dose + corticosteroid taper + tacrolimus + MMF	Preloading Induction with Thymoglobulin® X 3 doses given day -4 (1.5mg/kg), day -2 (1.5mg/kg), and day 0 (3mg/kg) + corticosteroid taper + tacrolimus + MMF anti-thymocyte globulin (rabbit) : Preloading Induction with Thymoglobulin® X 3 doses given day -4 (1.5mg/kg), day -2 (1.5mg/kg), and day 0 (3mg/kg) + corticosteroid taper + tacrolimus + MMF
Measure Participants	6	5
Acute rejection	1 16.7%	1 20%
Patient Death	0 0%	0 0%
Graft Loss	0 0%	0 0%

2. Secondary Outcome

Title	Incidence of Treatment Failures: Defined as the Percentage of Patients That do Not Remain on Initial Therapy.
Time Frame	Ongoing

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Incidence of Infections
Time Frame	Not defined

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Need for Antilymphocyte Antibody Therapy to Treat Acute Rejection
Time Frame	Not defined

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Severity of Biopsy-proven Rejection Using Banff 97 Criteria
Time Frame	Not defined

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Serum Creatinine
Time Frame	Post-operative days 1-7, 30, 90 and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Malignancy
Time Frame	Undefined

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Preloading Induction With Thymoglobulin		Preloading Induction With Thymoglobulin® X 3 Doses
Arm/Group Description	Preloading Induction with Thymoglobulin® X 4 doses given day -4, day -2, day 0, and day 2 at 1.5 mg/kg/dose + corticosteroid taper + tacrolimus + MMF anti-thymocyte globulin (rabbit) : Preloading Induction with Thymoglobulin® X 4 doses given day -4, day -2, day 0, and day 2 at 1.5 mg/kg/dose + corticosteroid taper + tacrolimus + MMF		Preloading Induction with Thymoglobulin® X 3 doses given day -4 (1.5mg/kg), day -2 (1.5mg/kg), and day 0 (3mg/kg) + corticosteroid taper + tacrolimus + MMF anti-thymocyte globulin (rabbit) : Preloading Induction with Thymoglobulin® X 3 doses given day -4 (1.5mg/kg), day -2 (1.5mg/kg), and day 0 (3mg/kg) + corticosteroid taper + tacrolimus + MMF
All Cause Mortality
	Preloading Induction With Thymoglobulin		Preloading Induction With Thymoglobulin® X 3 Doses
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Preloading Induction With Thymoglobulin		Preloading Induction With Thymoglobulin® X 3 Doses
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/6 (33.3%)		3/5 (60%)
Renal and urinary disorders
Banff 1A Rejection	1/6 (16.7%)	1	0/5 (0%)	0
Renal Allograft Dysfunction	1/6 (16.7%)	1	0/5 (0%)	0
Acute Renal Failure / Anemia	0/6 (0%)	0	1/5 (20%)	2
Fever/Acute Renal Failure/Acidosis	0/6 (0%)	0	1/5 (20%)	3
Increased Serum Creatinine	0/6 (0%)	0	1/5 (20%)	1
Other (Not Including Serious) Adverse Events
	Preloading Induction With Thymoglobulin		Preloading Induction With Thymoglobulin® X 3 Doses
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/6 (66.7%)		3/5 (60%)
Gastrointestinal disorders
Nausea/Vomiting	0/6 (0%)	0	1/5 (20%)	1
General disorders
Body Aches	1/6 (16.7%)	1	1/5 (20%)	1
Immune system disorders
Fever / Chills	4/6 (66.7%)	4	3/5 (60%)	3
Fever > 102°F	1/6 (16.7%)	1	1/5 (20%)	1
Investigations
PLT < 100,000 cells/mm3	1/6 (16.7%)	1	1/5 (20%)	1
Vascular disorders
Hypertension	1/6 (16.7%)	1	1/5 (20%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.