Low Dose Thymoglobin in Renal Transplant Patients

• Sponsor: Lahey Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT01280617
• Collaborator: Brigham and Women's Hospital (Other)
• Enrollment: 44
• Location: 1
• Arms: 2
• Duration (Months): 39
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

This is a planned single center prospective randomized study evaluating the safety and efficacy of low dose thymoglobulin as induction agent in renal transplant recipients. Inclusion criteria will be adult renal transplant recipients who are not sensitized against their potential donors. The patients who agree to participate in the study will be randomly assigned to either thymoglobulin at 1.25mg/kg x 3 doses or 0.75mg/kg x 3 doses. There will be 86 sealed envelopes to perform the randomization process. 43 envelopes with 1.25mg/kg dosing and the other 43 envelopes with 0.75mg/kg dosing. The investigators will sequentially choose the sealed envelopes at the time of the patient randomization process. All patients will be started on our standard immunosupression regimen of prograf/cellcept and a fast steroid taper. Data will be obtained from every patient for up to one year post-transplant.

Condition or Disease	Intervention/Treatment	Phase
Acute Renal Failure	Drug: Thymoglobulin; Drug: Thymoglobulin 0.75mg/kg dose	N/A

Detailed Description

Detailed Study Design:

This is a planned single center prospective randomized study evaluating the safety and efficacy of low dose thymoglobulin as induction agent in renal transplant recipients. Inclusion criteria will be adult renal transplant recipients who are not sensitized against their potential donors. The patients who agree to participate in the study will be randomly assigned to either thymoglobulin at 1.25mg/kg x 3 doses or 0.75mg/kg x 3 doses. There will be 86 sealed envelopes to perform the randomization process. 43 envelopes with 1.25mg/kg dosing and the other 43 envelopes with 0.75mg/kg dosing. The investigators will sequentially choose the sealed envelopes at the time of the patient randomization process. All patients will be started on our standard immunosupression regimen of prograf/cellcept and a fast steroid taper. Data will be obtained from every patient for up to one year post-transplant.

The investigators will obtain the following information at the time of consent:

1. Type of renal transplant (living vs cadaveric)

2. HLA matching

3. CMV status of donor and recipient

4. EBV status of donor and recipient

5. Creatinine prior to transplantation

6. Urinalysis at the time of transplantation

7. Primary renal disease

8. Weight of the renal transplant

9. BMI of the recipient and donor

10. Age of the donor and recipient

11. Sex of the donor and recipient

12. White blood cell count

13. Hemoglobin

14. Platelets

15. History of infections

16. History of malignancies

During each of the clinic visits the investigators will obtain the following information:

1. Creatinine

2. Urinalysis

3. White blood cell count

4. Hemoglobin

5. Platelets

6. Weight of the recipient

7. Infections

8. Malignancies

9. Renal biopsy report if a biopsy was performed

In addition to the standard of care laboratories, the investigators will ask patients to give us 7 additional green tubes, one purple tube and two red tubes which will be drawn at the time of standard of care laboratories pre-transplantation, 3 months post-transplant, 6 months post-transplant and 12 months post-transplant. This tubes will be used to measure CD4, CD8, CD19, CD20, CD68 cells as these are cells that are believed to be affected by the use of thymoglobulin.

If the patient is to have a renal transplant biopsy at any time during the 12 months of the study, any excess tissue may be utilized for staining of special cell markers including CD4, CD8, CD19, CD20 and CD68.

Subject inclusion criteria: Potential adult renal transplant recipients

Subject exclusion criteria: Sensitized renal transplant recipients

Methods of statistical analysis to be employed in preparation of reports:

The investigators are planning a study with 1 control per experimental subject, an accrual interval of 24 time units, and additional follow-up after the accrual interval of 12 time units. In a previous study the median survival time on the control treatment was 36 time units. If the true hazard ratio (relative risk) of control subjects relative to experimental subjects is 5, the investigators will need to study 43 experimental subjects and 43 control subjects to be able to reject the null hypothesis that the experimental and control survival curves are equal with probability (power) .800. The Type I error probability associated with this test of this null hypothesis is 0.05. T-tests will be used to compare both groups.

Thymoglobulin (rabbit antithymocyte globulin) is FDA approved for the treatment of acute cellular rejection. Nevertheless, for at least the past 10 years this medication has been utilized as induction agent in renal transplant recipients. This is because an induction agent allows prednisone withdrawal in renal transplant recipients.

Prednisone withdrawal is extremely important in renal transplant recipients as old protocols that allowed long term prednisone use compromised the long term health of renal transplant recipients. Not only does prednisone increase markedly the risk of development of diabetes and osteoporosis, but is also increases drastically the risk of fractures, which is a very common cause of mortality in long term prednisone renal transplant recipients.

Study Design

• Study Type: Interventional
• Actual Enrollment: 44 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Low Dose Thymoglobulin As Induction Agent on Prednisone-Free Regimens of Renal Transplant Recipients
• Study Start Date: Oct 1, 2010
• Actual Primary Completion Date: Nov 1, 2013
• Actual Study Completion Date: Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Thymoglobulin 1.25mg/kg dose The safety and efficacy of low dose Thymoglobulin (1.25mg/kg) as an induction agent in renal transplant subjects.	Drug: Thymoglobulin; Thymoglobulin 1.25mg/kg dose
Experimental: Thymoglobulin 0.75mg/kg dose The safety and efficacy of low dose Thymoglobulin (0.75mg/kg) as an induction agent in renal transplant subjects.	Drug: Thymoglobulin 0.75mg/kg dose; Thymoglobulin; Other Names: Thymoglobulin

Outcome Measures

Primary Outcome Measures

1. Rates of Acute Cellular Rejection Between Study Group [1 year from date of transplant]

   Incidence of Biopsy Proven Acute Rejection at 1 year post transplant:

Secondary Outcome Measures

1. , "Total Number of Adverse Events, Including Any Infections, Leucopenia, and Malignancy" [1 year from date of transplant]

   Number of individual adverse events in high versus low dose Thymoglobulin groups will be tabulated and statistical analyses performed

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Potential Adult Renal Transplant Patients -

Exclusion Criteria:

Sensitized Renal Transplant Patients

-

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Lahey Clinic	Burlington	Massachusetts	United States	01805

Sponsors and Collaborators

• Lahey Clinic
• Brigham and Women's Hospital

Investigators

• Principal Investigator: Simpson, Lahey Hospital & Medical Ctr

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Lahey Clinic
• ClinicalTrials.gov Identifier: NCT01280617
• Other Study ID Numbers: 2010-065
• First Posted: Jan 21, 2011
• Last Update Posted: Mar 16, 2021
• Last Verified: Feb 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Lahey Clinic: Renal Transplant; Thymoglubulin
• Additional relevant MeSH terms: Acute Kidney Injury; Thymoglobulin; Antilymphocyte Serum

Study Results

Participant Flow

Recruitment Details	All unsensitized renal transplant recipients were considered eligible and were approached for consent. Inclusion dates were October 2010 until April 2013. A total of 58 patients were approached; 44 consented and were enrolled in the protocol

Arm/Group Title	Thymoglobulin 1.25mg/kg Dose	Thymoglobulin 0.75mg/kg Dose
Arm/Group Description	The safety and efficacy of low dose Thymoglobulin (1.25mg/kg) as an induction agent in renal transplant subjects. Thymoglobulin: Thymoglobulin 1.25mg/kg dose	The safety and efficacy of low dose Thymoglobulin (0.75mg/kg) as an induction agent in renal transplant subjects. Thymoglobulin 0.75mg/kg dose: Thymoglobulin
Period Title: Overall Study
STARTED	23	21
COMPLETED	23	20
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Thymoglobulin 1.25mg/kg Dose	Thymoglobulin 0.75mg/kg Dose	Total
Arm/Group Description	The safety and efficacy of low dose Thymoglobulin (1.25mg/kg) as an induction agent in renal transplant subjects. Thymoglobulin: Thymoglobulin 1.25mg/kg dose	The safety and efficacy of low dose Thymoglobulin (0.75mg/kg) as an induction agent in renal transplant subjects. Thymoglobulin 0.75mg/kg dose: Thymoglobulin	Total of all reporting groups
Overall Participants	23	20	43
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	23 100%	17 85%	40 93%
>=65 years	0 0%	3 15%	3 7%
Sex/Gender, Customized (Count of Participants)
males	16 69.6%	16 80%	32 74.4%
females	7 30.4%	4 20%	11 25.6%

Outcome Measures

1. Primary Outcome

Title	Rates of Acute Cellular Rejection Between Study Group
Description	Incidence of Biopsy Proven Acute Rejection at 1 year post transplant:
Time Frame	1 year from date of transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Thymoglobulin 1.25mg/kg Dose	Thymoglobulin 0.75mg/kg Dose
Arm/Group Description	Thymoglobulin 1.25mg/kg dose All Cause mortality 0/23	Thymoglobulin 0.75mg/kg dose All Cause Mortality 3/20 - 2 with pre-existing cardiac disease, diabetes, and history of smoking
Measure Participants	23	20
Number [Number of rejection]	4	2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Thymoglobulin 1.25mg/kg Dose, Thymoglobulin 0.75mg/kg Dose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	t-test, 2 sided
	Comments	Continuous variables analyzed using 2-tailed t test or Mann Whitney tes.. Categorical variables analyzed using Chi-Square or Fisher's Exact test

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Thymoglobulin 1.25mg/kg Dose, Thymoglobulin 0.75mg/kg Dose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	, "Total Number of Adverse Events, Including Any Infections, Leucopenia, and Malignancy"
Description	Number of individual adverse events in high versus low dose Thymoglobulin groups will be tabulated and statistical analyses performed
Time Frame	1 year from date of transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Thymoglobulin 1.25mg/kg Dose	Thymoglobulin 0.75mg/kg Dose
Arm/Group Description	Thymoglobulin 1.25mg/kg dose All Cause mortality 0/23	Thymoglobulin 0.75mg/kg dose All Cause Mortality 3/20 - 2 with pre-existing cardiac disease, diabetes, and history of smoking
Measure Participants	23	20
Number [Adverse Events]	3	8

Adverse Events

Time Frame	Day of kidney transplant until end of first post transplant year
Arm/Group Title	Thymoglobulin 1.25mg/kg Dose		Thymoglobulin 0.75mg/kg Dose
Arm/Group Description	Thymoglobulin 1.25mg/kg dose All Cause mortality 0/23		Thymoglobulin 0.75mg/kg dose All Cause Mortality 3/20 - 2 with pre-existing cardiac disease, diabetes, and history of smoking
All Cause Mortality
	Thymoglobulin 1.25mg/kg Dose		Thymoglobulin 0.75mg/kg Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		3/20 (15%)
Serious Adverse Events
	Thymoglobulin 1.25mg/kg Dose		Thymoglobulin 0.75mg/kg Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/23 (13%)		2/20 (10%)
Infections and infestations
Serious Infections	3/23 (13%)	3	2/20 (10%)	2
Other (Not Including Serious) Adverse Events
	Thymoglobulin 1.25mg/kg Dose		Thymoglobulin 0.75mg/kg Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/23 (13%)		8/20 (40%)
Renal and urinary disorders
Delayed Graft Function	3/23 (13%)	3	8/20 (40%)	8

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.