Kidney Failure, ChronicPhase 3NCT00275509
Induction Therapy Study in Live Donor Kidney Transplant Recipients With a Positive Crossmatch
A Phase 3 study testing Thymoglobulin, Daclizumab and Plasmapheresis in people with Kidney Failure, Chronic, run by Johns Hopkins University at 1 site in United States.
Trial summary
The purpose of this study is to determine whether the anti-T cell antibody, Thymoglobulin is a more effective induction medication than the anti-IL-2R inhibitor daclizumab, in kidney transplant recipients who have a positive crossmatch with their live donor. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kidney Failure, Chronic
- What is being tested?
- Thymoglobulin, Daclizumab and Plasmapheresis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2007to Jun 2010
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult (18 years or older)
- End-stage renal disease
- Identified to have positive lymphocytotoxic crossmatch or flow cytometric crossmatch with live donor
Who cannot join
- Deceased donor recipients
- Pregnancy
- Active infection
- History of cancer within the past two years (with the exception of non-melanomatous skin cancer)
- History of heparin induced thrombocytopenia
- Medical contraindications to transplant procedure
Trial locations and contacts
1 site in 1 country.
United States1 site
The Johns Hopkins University, School of Medicine
Baltimore, Maryland, 21205
About this study
Official title: Open Label Randomized Study of Thymoglobulin Versus Daclizumab Induction Therapies for the Reduction of Acute Rejection in Live Donor Kidney Transplant Recipients With a Positive Crossmatch
The purpose of this study is to determine whether the anti-T cell antibody, Thymoglobulin is a more effective induction medication than the anti-IL-2R inhibitor daclizumab, in kidney transplant recipients who have a positive crossmatch with their live donor.
Read the detailed description
Kidney transplantation is widely recognized as the optimal therapy for the management of end-stage renal disease. Presently, the deceased donor kidney waiting list has expanded disproportionately with the number of transplant procedures that are performed in the United States. To further compound this problem, as many as 1/3 of the patients on this list are highly sensitized against a broad range of potential donors.
In order to address this problem, we developed an antibody depletion protocol that permits transplantation in patients who have a positive crossmatch with their live donor. The protocol consists of standard immunosuppressant therapy, plasmapheresis, and intravenous immunoglobulin infusion. We have successfully performed transplantation in over 100 such patients with low complication rates.
Because these patients have been exposed to their donor's human leukocyte antigen (HLA) they are at high risk for both acute cellular and acute antibody-mediated rejection. This intent of this prospective, randomized, open-label trial is to determine whether induction therapy (i.e. therapy given at the time of transplantation for prophylaxis) with Thymoglobulin is associated with a lower 6-month incidence of acute cellular and antibody-mediated rejection than with our standard therapy, daclizumab.
- Conditions
- Kidney Failure, Chronic
- Being tested
- Thymoglobulin, Daclizumab, Plasmapheresis, Mycophenolate mofetil, Tacrolimus
- Keywords
- kidney, transplantation, positive crossmatch, antibody mediated rejection, rejection, induction, therapy, trial
- Medical subject headings
- Kidney Failure, Chronic, Rejection, Psychology
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ThymoglobulinDrug
DaclizumabDrug
PlasmapheresisOther
Following each plasmapheresis session, 100 mg/kg of Cytogam (CMVIg) (Cytogam, CSL Behring, King of Prussia, PA) was administered
2 gm/day. Standard of care
TacrolimusDrug
To achieve serum level of 8-10 ng/ml.
DexamethasoneDrug
100 mg intra-operatively, and 25 mg every 6h post-operatively for six doses
PrednisoneDrug
Taper over three months to 5 mg daily
CytogamDrug
Following each plasmapheresis session, 100 mg/kg of Cytogam (CMVIg) (Cytogam, CSL Behring, King of Prussia, PA) was administered
| Study group | Role | What they receive |
|---|---|---|
| Thymoglobulin | Experimental | Thymoglobulin was administered as 1.5 mg/kg prior to reperfusion followed by 6 post-operative doses on days 1 through 6. Receives: Drug: Thymoglobulin; Other: Plasmapheresis; Drug: Mycophenolate mofetil; Drug: Tacrolimus; Drug: Dexamethasone; Drug: Prednisone; Drug: Cytogam |
| Daclizumab | Experimental | Daclizumab was administered as 2 mg/kg prior to reperfusion followed by 1 mg/kg every other week for 8 weeks post-operatively (4 post-operative doses). Receives: Drug: Daclizumab; Other: Plasmapheresis; Drug: Mycophenolate mofetil; Drug: Tacrolimus; Drug: Dexamethasone; Drug: Prednisone; Drug: Cytogam |
What is being measured
The primary outcome is the main question the study is designed to answer.
6-month Acute Cellular-mediated Rejection Rate (CMR)
Per 2007 international Banff Classification Criteria, CMR 1A was diagnosed on biopsies displaying significant interstitial infiltration (>25% of parenchyma affected, i2 or i3) and foci of moderate tubulitis (t2). CMR IB was diagnosed in cases with significant interstitial infiltration (>25% of parenchyma affected, i2 or i3) and foci of severe tubulitis (t3). CMR IIA were cases with mild-to-moderate intimal arteritis (v1), while CMR IIB were those with severe intimal arteritis comprising >25% of the luminal area (v2). CMR III were those cases with transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic inflammation (v3).
Measured: Up to 6 months
6-month Acute Antibody-mediated Rejection Rate (AMR)
A diagnosis of AMR was based on the 2013 international Banff Classification Criteria and is defined as the presence of circulating donor-specific antibody (DSA) and either: 1) peritubular capillary staining of C4d and at least one of the following: peritubular capillaritis (ptc) score>0, glomerulitis (g) score>0, acute thrombotic microangiopathy (TMA) in the absence of any other cause, or other features consistent with AMR (endothelial injury, fibrin thrombi, microinfarctions, interstitial hemorrhage), or 2) absence of capillary staining of C4d and the presence of ptc>0 and g>0 or ptc>0 or g>0 and acute TMA, in the absence of any other cause of TMA.
Measured: Up to 6 months
6-month Cumulative Rejection Incidence (Either CMR, AMR or Both)
Biopsy shows evidence of either AMR or CMR or evidence both.
Measured: Up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2006 (estimated)
- Study startJan 2007
- Primary completionJun 2010
- Study completionJun 2010
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 (2)Papers the sponsor has linked to this study.
- Other trials for Kidney Failure, ChronicStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Robert A Montgomery, M.D., Ph.D., Principal investigator, Johns Hopkins University , SOMChristopher E Simpkins, M.D., Study director, Johns Hopkins University, SOM
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00275509
- Sponsor's protocol ID
- IRB00078055
- Status last verified
- Dec 2017
- First submitted
- 10 Jan 2006
- Last updated
- 18 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Haas M, Sis B, Racusen LC, Solez K, Glotz D, Colvin RB, Castro MC, David DS, David-Neto E, Bagnasco SM, Cendales LC, Cornell LD, Demetris AJ, Drachenberg CB, Farver CF, Farris AB 3rd, Gibson IW, Kraus E, Liapis H, Loupy A, Nickeleit V, Randhawa P, Rodriguez ER, Rush D, Smith RN, Tan CD, Wallace WD, Mengel M; Banff meeting report writing committee. Banff 2013 meeting report: inclusion of c4d-negative antibody-mediated rejection and antibody-associated arterial lesions. Am J Transplant. 2014 Feb;14(2):272-83. doi: 10.1111/ajt.12590.
PubMed 24472190Solez K, Colvin RB, Racusen LC, Haas M, Sis B, Mengel M, Halloran PF, Baldwin W, Banfi G, Collins AB, Cosio F, David DS, Drachenberg C, Einecke G, Fogo AB, Gibson IW, Glotz D, Iskandar SS, Kraus E, Lerut E, Mannon RB, Mihatsch M, Nankivell BJ, Nickeleit V, Papadimitriou JC, Randhawa P, Regele H, Renaudin K, Roberts I, Seron D, Smith RN, Valente M. Banff 07 classification of renal allograft pathology: updates and future directions. Am J Transplant. 2008 Apr;8(4):753-60. doi: 10.1111/j.1600-6143.2008.02159.x. Epub 2008 Feb 19.
PubMed 18294345
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Label Randomized Study of Thymoglobulin Versus Daclizumab Induction Therapies for the Reduction of Acute Rejection in Live Donor Kidney Transplant Recipients With a Positive Crossmatch
- ClinicalTrials.gov ID
- NCT00275509
- Acronym / sponsor ID
- IRB00078055
- Conditions
- Kidney Failure, Chronic
- Keywords
- kidney, transplantation, positive crossmatch, antibody mediated rejection, rejection, induction, therapy, trial
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Study start
- Jan 2007 (actual)
- Primary completion
- Jun 2010 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 12 Jan 2006 (estimated)
- Results
- Posted 20 Dec 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether the anti-T cell antibody, Thymoglobulin is a more effective induction medication than the anti-IL-2R inhibitor daclizumab, in kidney transplant recipients who have a positive crossmatch with their live donor.
Detailed description
Kidney transplantation is widely recognized as the optimal therapy for the management of end-stage renal disease. Presently, the deceased donor kidney waiting list has expanded disproportionately with the number of transplant procedures that are performed in the United States. To further compound this problem, as many as 1/3 of the patients on this list are highly sensitized against a broad range of potential donors.
In order to address this problem, we developed an antibody depletion protocol that permits transplantation in patients who have a positive crossmatch with their live donor. The protocol consists of standard immunosuppressant therapy, plasmapheresis, and intravenous immunoglobulin infusion. We have successfully performed transplantation in over 100 such patients with low complication rates.
Because these patients have been exposed to their donor's human leukocyte antigen (HLA) they are at high risk for both acute cellular and acute antibody-mediated rejection. This intent of this prospective, randomized, open-label trial is to determine whether induction therapy (i.e. therapy given at the time of transplantation for prophylaxis) with Thymoglobulin is associated with a lower 6-month incidence of acute cellular and antibody-mediated rejection than with our standard therapy, daclizumab.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Thymoglobulin | Experimental | Drug: Thymoglobulin, Other: Plasmapheresis, Drug: Mycophenolate mofetil, Drug: Tacrolimus, Drug: Dexamethasone, Drug: Prednisone, Drug: CytogamThymoglobulin was administered as 1.5 mg/kg prior to reperfusion followed by 6 post-operative doses on days 1 through 6. |
| Daclizumab | Experimental | Drug: Daclizumab, Other: Plasmapheresis, Drug: Mycophenolate mofetil, Drug: Tacrolimus, Drug: Dexamethasone, Drug: Prednisone, Drug: CytogamDaclizumab was administered as 2 mg/kg prior to reperfusion followed by 1 mg/kg every other week for 8 weeks post-operatively (4 post-operative doses). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Adult (18 years or older)
- End-stage renal disease
- Identified to have positive lymphocytotoxic crossmatch or flow cytometric crossmatch with live donor
Key exclusion criteria (6 listed)
- Deceased donor recipients
- Pregnancy
- Active infection
- History of cancer within the past two years (with the exception of non-melanomatous skin cancer)
- History of heparin induced thrombocytopenia
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 |
|---|---|---|
| Thymoglobulin | Drug | Thymoglobulin |
| Daclizumab | Drug | Daclizumab |
| PlasmapheresisFollowing each plasmapheresis session, 100 mg/kg of Cytogam (CMVIg) (Cytogam, CSL Behring, King of Prussia, PA) was administered | Other | Daclizumab, Thymoglobulin |
| Mycophenolate mofetil2 gm/day. Standard of care | Drug | Daclizumab, Thymoglobulin |
| TacrolimusTo achieve serum level of 8-10 ng/ml. | Drug | Daclizumab, Thymoglobulin |
| Dexamethasone100 mg intra-operatively, and 25 mg every 6h post-operatively for six doses | Drug | Daclizumab, Thymoglobulin |
| PrednisoneTaper over three months to 5 mg daily | Drug | Daclizumab, Thymoglobulin |
| CytogamFollowing each plasmapheresis session, 100 mg/kg of Cytogam (CMVIg) (Cytogam, CSL Behring, King of Prussia, PA) was administered | Drug | Daclizumab, Thymoglobulin |
Primary outcome
6-month Acute Cellular-mediated Rejection Rate (CMR)
Time frame: Up to 6 months
Per 2007 international Banff Classification Criteria, CMR 1A was diagnosed on biopsies displaying significant interstitial infiltration (>25% of parenchyma affected, i2 or i3) and foci of moderate tubulitis (t2). CMR IB was diagnosed in cases with significant interstitial infiltration (>25% of parenchyma affected, i2 or i3) and foci of severe tubulitis (t3). CMR IIA were cases with mild-to-moderate intimal arteritis (v1), while CMR IIB were those with severe intimal arteritis comprising >25% of the luminal area (v2). CMR III were those cases with transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic inflammation (v3).
6-month Acute Antibody-mediated Rejection Rate (AMR)
Time frame: Up to 6 months
A diagnosis of AMR was based on the 2013 international Banff Classification Criteria and is defined as the presence of circulating donor-specific antibody (DSA) and either: 1) peritubular capillary staining of C4d and at least one of the following: peritubular capillaritis (ptc) score>0, glomerulitis (g) score>0, acute thrombotic microangiopathy (TMA) in the absence of any other cause, or other features consistent with AMR (endothelial injury, fibrin thrombi, microinfarctions, interstitial hemorrhage), or 2) absence of capillary staining of C4d and the presence of ptc>0 and g>0 or ptc>0 or g>0 and acute TMA, in the absence of any other cause of TMA.
6-month Cumulative Rejection Incidence (Either CMR, AMR or Both)
Time frame: Up to 6 months
Biopsy shows evidence of either AMR or CMR or evidence both.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 24472190Haas M, Sis B, Racusen LC, Solez K, Glotz D, Colvin RB, Castro MC, David DS, David-Neto E, Bagnasco SM, Cendales LC, Cornell LD, Demetris AJ, Drachenberg CB, Farver CF, Farris AB 3rd, Gibson IW, Kraus E, Liapis H, Loupy A, Nickeleit V, Randhawa P, Rodriguez ER, Rush D, Smith RN, Tan CD, Wallace WD, Mengel M; Banff meeting report writing committee. Banff 2013 meeting report: inclusion of c4d-negative antibody-mediated rejection and antibody-associated arterial lesions. Am J Transplant. 2014 Feb;14(2):272-83. doi: 10.1111/ajt.12590.
- Background: PubMed 18294345Solez K, Colvin RB, Racusen LC, Haas M, Sis B, Mengel M, Halloran PF, Baldwin W, Banfi G, Collins AB, Cosio F, David DS, Drachenberg C, Einecke G, Fogo AB, Gibson IW, Glotz D, Iskandar SS, Kraus E, Lerut E, Mannon RB, Mihatsch M, Nankivell BJ, Nickeleit V, Papadimitriou JC, Randhawa P, Regele H, Renaudin K, Roberts I, Seron D, Smith RN, Valente M. Banff 07 classification of renal allograft pathology: updates and future directions. Am J Transplant. 2008 Apr;8(4):753-60. doi: 10.1111/j.1600-6143.2008.02159.x. Epub 2008 Feb 19.
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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.
Robert A Montgomery, M.D., Ph.D. principal investigator
Johns Hopkins University , SOM
Christopher E Simpkins, M.D. study director
Johns Hopkins University, SOM
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Thymoglobulin, Daclizumab and Plasmapheresis in people with Kidney Failure, Chronic, run by Johns Hopkins University at 1 site 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 3 inclusion and 6 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 18 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 20 Dec 2017). 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?
6-month Acute Cellular-mediated Rejection Rate (CMR) (time frame: Up to 6 months). The study lists 3 primary outcomes in all. 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 NCT00275509, which also lists 2 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 18 Jan 2018; AzTrials last refreshed its copy on 6 Nov 2026.