End-Stage Renal DiseasePhase 2STATNCT00906204
Safety Trial of Single Versus Multiple Dose Thymoglobulin Induction in Kidney Transplantation
A Phase 2 study testing Single-dose rabbit Anti-thymocyte Globulin induction and Divided-dose rabbit Anti-thymocyte Globulin induction in people with End-Stage Renal Disease and Kidney Failure, run by Wright State University at 4 sites in United States.
Trial summary
In a non-blinded pilot study conducted at the University of Nebraska Medical Center, evidence was found that a single large dose of Thymoglobulin on the day of kidney transplantation produced better kidney function than the standard dosing plan, when the same amount is divided into smaller doses on 4 days. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- End-Stage Renal Disease, Kidney Failure
- What is being tested?
- Single-dose rabbit Anti-thymocyte Globulin induction and Divided-dose rabbit Anti-thymocyte Globulin induction
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 99 participants
- Where
- 4 sitesUnited States
- Study dates
- Mar 2010to Jul 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject capable of giving written informed consent, with end-stage kidney disease, who is a suitable candidate for primary kidney transplantation
- Male or female subject who has reached legal age in the state where they reside and is at least 18 years of age
- Deceased or living donors
- Compatible ABO blood type
- Expanded-criteria donor (ECD) kidneys with a donor grade score of ≤ 25 (as developed by Nyberg, et al.)
- If Kidneys are pumped, they must meet the following pumping parameters: resistance <0.35 with a flow rate of >60 ml/min.
Who cannot join
- Recipient age >65 years
- PRA >50%, or donor-specific antibody
- CIT >30 hours
- Re-transplant patients
- Multi-organ transplant recipients (example: kidney/pancreas or kidney/liver)
- Renal transplant recipients planned for future pancreas transplantation
Show all 21Show fewer
- Current unstable cardiovascular disease or history of myocardial infarction within the previous 6 months
- Current malignancy or history or malignancy (within the previous 5 years) with the exception of non-metastatic basal or squamous cell carcinoma of the skin or carcinoma in-situ of the cervix that has been treated successfully.
- Hepatitis B and C recipients or active liver disease
- HIV positive recipients
- Primary disease requiring treatment with steroids after transplantation
- Expanded-criteria donor kidneys (current UNOS criteria) with a donor grade score of > 25
- Donation after cardiac death (DCD) donors
- Dual adult kidneys
- Recipients of pediatric (age <12 years) unilateral or en-bloc kidneys
- Previous treatment with rATG
- Known hypersensitivity, extensive exposure, or allergy to rabbits
- Pregnant
- Any condition that in the investigator's opinion may compromise study participation (e.g., history or likelihood of non-compliance with immunosuppression regimen, protocol visits, tests, and studies)
- Relative Exclusion Criteria:
- Patients with a BMI > 37 should be considered on an individual basis based on overall health and body habitus.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
The Methodist Hospital Research Institute
Houston, Texas, 77030
University of Nebraska Medical Center
Omaha, Nebraska, 68198
University of Arizona
Tucson, Arizona, 85724
Wake Forest University
Winston-Salem, North Carolina, 27157
About this study
Official title: Prospective, Randomized, Double-Blind, Double-Dummy, Multicenter Trial to Assess Safety of Single Dose vs. Traditional Administration of Thymoglobulin Induction for Renal Transplantation
In a non-blinded pilot study conducted at the University of Nebraska Medical Center, evidence was found that a single large dose of Thymoglobulin on the day of kidney transplantation produced better kidney function than the standard dosing plan, when the same amount is divided into smaller doses on 4 days. This new study repeats that dose comparison, but with double-blinding and at multiple transplantation centers.
Read the detailed description
This study is designed to confirm the one-year safety of single-dose rabbit anti-thymocyte globulin induction at kidney transplantation, compared to the conventional administration of the same overall dose divided into four smaller doses across four days. Two randomized groups of kidney transplant recipients will be each administered the drug Thymoglobulin according to a different dosing regimen. The control group will receive the usual and traditional regimen of a total of 6 mg/Kg divided into 4 doses, 1 on the day of transplantation and 1 each day on the next 3 days. The experimental group will receive the same total Thymoglobulin dose, 6 mg/Kg, but entirely on the day of transplantation.
The study will be double-blinded, with placebo doses of Thymoglobulin administered as needed to enrollees in the experimental group. Enrollment is targeted at 165, with 150 subjects needed to complete the study for adequate evaluation.
- Conditions
- End-Stage Renal Disease, Kidney Failure
- Being tested
- Single-dose rabbit Anti-thymocyte Globulin induction, Divided-dose rabbit Anti-thymocyte Globulin induction
- Keywords
- Renal transplantation, Kidney transplantation
- Medical subject headings
- Kidney Failure, Chronic, Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Single-dose rabbit Anti-thymocyte Globulin inductionBiological
Also called Thymoglobulin, rATG
6 mg of rATG administered in a single dose on the day of kidney transplantation
Divided-dose rabbit Anti-thymocyte Globulin inductionBiological
Also called Thymoglobulin, rATG
6 mg/kg total rabbit Anti-thymocyte Globulin dose administered as 1.5 mg/kg doses on 4 sequential days, beginning on the day of kidney transplantation.
| Study group | Role | What they receive |
|---|---|---|
| Single-dose Thymoglobulin | Experimental | Biological/Vaccine Single-dose rabbit Anti-thymocyte Globulin induction, 6 mg/kg IV infusion Receives: Biological: Single-dose rabbit Anti-thymocyte Globulin induction |
| Divided-dose Thymoglobulin | Active comparator | Biological/Vaccine Divided-dose rabbit Anti-thymocyte Globulin induction, 1.5 mg/kg IV infusion QD x 4 Receives: Biological: Divided-dose rabbit Anti-thymocyte Globulin induction |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite Endpoint of 5 Components: Fever, Hypoxia, Hypotension, Cardiac Events, and Delayed Graft Function
The composite endpoint components and definitions are:
- Fever: Body temperature ≥ 38.5˚C.
- Hypotension: After rATG initiation, systolic blood pressure ≤ 90 mmHg requiring de novo treatment with vasopressors.
- Hypoxia: During transplantation surgery, increase in FiO2 to ≥ 60% following rATG initiation. Following transplantation, starting in recovery room, FiO2 ≥ 50% or nasal cannula delivering ≥ 3 liters, either singly or combined, for > 12 hours out of a 24 hour period.
- Cardiac events: Myocardial Infarction, clinically significant dysrhythmia (atrial fibrillation, atrial flutter, ventricular fibrillation and ventricular tachycardia)
- Delayed graft function (DGF): Requirement for dialysis within 7 days of transplantation
Measured: During first 7 days after kidney transplantation
Secondary outcomes (5)
Patient Survival
Kaplan-Meier estimate of the number of patients who survived for the 12 months after kidney transplantation.
Measured: 12 months post-transplantation
Graft Survival
Kaplan-Meier estimates of graft survival probability for 12 months after transplantation
Measured: 12 months post-transplantation
Acute Kidney Rejection
Kaplan-Meier probability estimates of rejection rates
Measured: 12 months post-transplantation
Incomplete Thymoglobulin Infusion
Measured: First 7 days post-transplantation
Kidney Function
Estimated Glomerular Filtration Rate using the abbreviated MDRD formula (Modification of Diet in Renal Disease study)
Measured: 12 months post-transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2009 (estimated)
- Study startMar 2010
- Primary completionJul 2014
- Study completionJul 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for End-Stage Renal DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 99 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wright State University
- Sponsor type
- University, hospital or other
- Collaborators
- Sanofi, University of Arizona, Wake Forest University, University of Nebraska, The Methodist Hospital Research Institute
- Responsible party
- Principal investigator, R. Brian Stevens, MD, PhD, FACS, FAST, Wright State University
- Investigators
- R.Brian Stevens, MD, PhD, Principal investigator, Wright State University, Dayton, Ohio
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00906204
- Sponsor's protocol ID
- 183-09-FB
- Acronym
- STAT
- Status last verified
- Nov 2015
- First submitted
- 19 May 2009
- Last updated
- 7 Dec 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Stevens RB, Mercer DF, Grant WJ, Freifeld AG, Lane JT, Groggel GC, Rigley TH, Nielsen KJ, Henning ME, Skorupa JY, Skorupa AJ, Christensen KA, Sandoz JP, Kellogg AM, Langnas AN, Wrenshall LE. Randomized trial of single-dose versus divided-dose rabbit anti-thymocyte globulin induction in renal transplantation: an interim report. Transplantation. 2008 May 27;85(10):1391-9. doi: 10.1097/TP.0b013e3181722fad.
PubMed 18497677Stevens RB, Foster KW, Miles CD, Lane JT, Kalil AC, Florescu DF, Sandoz JP, Rigley TH, Nielsen KJ, Skorupa JY, Kellogg AM, Malik T, Wrenshall LE. A randomized 2x2 factorial trial, part 1: single-dose rabbit antithymocyte globulin induction may improve renal transplantation outcomes. Transplantation. 2015 Jan;99(1):197-209. doi: 10.1097/TP.0000000000000250.
PubMed 25083614Stevens RB, Wrenshall LE, Miles CD, Farney AC, Jie T, Sandoz JP, Rigley TH, Osama Gaber A. A Double-Blind, Double-Dummy, Flexible-Design Randomized Multicenter Trial: Early Safety of Single- Versus Divided-Dose Rabbit Anti-Thymocyte Globulin Induction in Renal Transplantation. Am J Transplant. 2016 Jun;16(6):1858-67. doi: 10.1111/ajt.13659. Epub 2016 Mar 7.
PubMed 26696251
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Randomized, Double-Blind, Double-Dummy, Multicenter Trial to Assess Safety of Single Dose vs. Traditional Administration of Thymoglobulin Induction for Renal Transplantation
- ClinicalTrials.gov ID
- NCT00906204
- Acronym / sponsor ID
- STAT / 183-09-FB
- Conditions
- End-Stage Renal Disease, Kidney Failure
- Keywords
- Renal transplantation, Kidney transplantation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 99 participants (actual)
- Lead sponsor
- Wright State UniversityUniversity, hospital or other
- Collaborators
- Sanofi, University of Arizona, Wake Forest University, University of Nebraska, The Methodist Hospital Research Institute
- Study start
- Mar 2010
- Primary completion
- Jul 2014 (actual)
- Study completion
- Jul 2014 (actual)
- First posted
- 21 May 2009 (estimated)
- Results
- Posted 7 Dec 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In a non-blinded pilot study conducted at the University of Nebraska Medical Center, evidence was found that a single large dose of Thymoglobulin on the day of kidney transplantation produced better kidney function than the standard dosing plan, when the same amount is divided into smaller doses on 4 days. This new study repeats that dose comparison, but with double-blinding and at multiple transplantation centers.
Detailed description
This study is designed to confirm the one-year safety of single-dose rabbit anti-thymocyte globulin induction at kidney transplantation, compared to the conventional administration of the same overall dose divided into four smaller doses across four days. Two randomized groups of kidney transplant recipients will be each administered the drug Thymoglobulin according to a different dosing regimen. The control group will receive the usual and traditional regimen of a total of 6 mg/Kg divided into 4 doses, 1 on the day of transplantation and 1 each day on the next 3 days. The experimental group will receive the same total Thymoglobulin dose, 6 mg/Kg, but entirely on the day of transplantation.
The study will be double-blinded, with placebo doses of Thymoglobulin administered as needed to enrollees in the experimental group. Enrollment is targeted at 165, with 150 subjects needed to complete the study for adequate evaluation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Single-dose Thymoglobulin | Experimental | Biological: Single-dose rabbit Anti-thymocyte Globulin inductionBiological/Vaccine Single-dose rabbit Anti-thymocyte Globulin induction, 6 mg/kg IV infusion |
| Divided-dose Thymoglobulin | Active comparator | Biological: Divided-dose rabbit Anti-thymocyte Globulin inductionBiological/Vaccine Divided-dose rabbit Anti-thymocyte Globulin induction, 1.5 mg/kg IV infusion QD x 4 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Subject capable of giving written informed consent, with end-stage kidney disease, who is a suitable candidate for primary kidney transplantation
- Male or female subject who has reached legal age in the state where they reside and is at least 18 years of age
- Deceased or living donors
- Compatible ABO blood type
- Expanded-criteria donor (ECD) kidneys with a donor grade score of ≤ 25 (as developed by Nyberg, et al.)
Key exclusion criteria (21 listed)
- Recipient age >65 years
- PRA >50%, or donor-specific antibody
- CIT >30 hours
- Re-transplant patients
- Multi-organ transplant recipients (example: kidney/pancreas or kidney/liver)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Single-dose rabbit Anti-thymocyte Globulin inductionAlso: Thymoglobulin, rATG6 mg of rATG administered in a single dose on the day of kidney transplantation | Biological | Single-dose Thymoglobulin |
| Divided-dose rabbit Anti-thymocyte Globulin inductionAlso: Thymoglobulin, rATG6 mg/kg total rabbit Anti-thymocyte Globulin dose administered as 1.5 mg/kg doses on 4 sequential days, beginning on the day of kidney transplantation. | Biological | Divided-dose Thymoglobulin |
Primary outcome
Composite Endpoint of 5 Components: Fever, Hypoxia, Hypotension, Cardiac Events, and Delayed Graft Function
Time frame: During first 7 days after kidney transplantation
The composite endpoint components and definitions are: * Fever: Body temperature ≥ 38.5˚C. * Hypotension: After rATG initiation, systolic blood pressure ≤ 90 mmHg requiring de novo treatment with vasopressors. * Hypoxia: During transplantation surgery, increase in FiO2 to ≥ 60% following rATG initiation. Following transplantation, starting in recovery room, FiO2 ≥ 50% or nasal cannula delivering ≥ 3 liters, either singly or combined, for > 12 hours out of a 24 hour period. * Cardiac events: Myocardial Infarction, clinically significant dysrhythmia (atrial fibrillation, atrial flutter, ventricular fibrillation and ventricular tachycardia) * Delayed graft function (DGF): Requirement for dialysis within 7 days of transplantation
5 secondary outcomes
Patient Survival
Time frame: 12 months post-transplantation
Graft Survival
Time frame: 12 months post-transplantation
Acute Kidney Rejection
Time frame: 12 months post-transplantation
Incomplete Thymoglobulin Infusion
Time frame: First 7 days post-transplantation
Kidney Function
Time frame: 12 months post-transplantation
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Dec 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 18497677Stevens RB, Mercer DF, Grant WJ, Freifeld AG, Lane JT, Groggel GC, Rigley TH, Nielsen KJ, Henning ME, Skorupa JY, Skorupa AJ, Christensen KA, Sandoz JP, Kellogg AM, Langnas AN, Wrenshall LE. Randomized trial of single-dose versus divided-dose rabbit anti-thymocyte globulin induction in renal transplantation: an interim report. Transplantation. 2008 May 27;85(10):1391-9. doi: 10.1097/TP.0b013e3181722fad.
- Background: PubMed 25083614Stevens RB, Foster KW, Miles CD, Lane JT, Kalil AC, Florescu DF, Sandoz JP, Rigley TH, Nielsen KJ, Skorupa JY, Kellogg AM, Malik T, Wrenshall LE. A randomized 2x2 factorial trial, part 1: single-dose rabbit antithymocyte globulin induction may improve renal transplantation outcomes. Transplantation. 2015 Jan;99(1):197-209. doi: 10.1097/TP.0000000000000250.
- Derived from this study: PubMed 26696251Stevens RB, Wrenshall LE, Miles CD, Farney AC, Jie T, Sandoz JP, Rigley TH, Osama Gaber A. A Double-Blind, Double-Dummy, Flexible-Design Randomized Multicenter Trial: Early Safety of Single- Versus Divided-Dose Rabbit Anti-Thymocyte Globulin Induction in Renal Transplantation. Am J Transplant. 2016 Jun;16(6):1858-67. doi: 10.1111/ajt.13659. Epub 2016 Mar 7.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
R.Brian Stevens, MD, PhD principal investigator
Wright State University, Dayton, Ohio
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Single-dose rabbit Anti-thymocyte Globulin induction and Divided-dose rabbit Anti-thymocyte Globulin induction in people with End-Stage Renal Disease and Kidney Failure, run by Wright State University at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Dec 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite Endpoint of 5 Components: Fever, Hypoxia, Hypotension, Cardiac Events, and Delayed Graft Function (time frame: During first 7 days after kidney transplantation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00906204, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Dec 2015.