Kidney TransplantationPhase 4NCT00246129
CamTac Trial:Campath-Tacrolimus vs IL2R MoAb/Tacrolimus/MMF in Renal Transplantation
A Phase 4 study testing Campath and Daclizumab in people with Kidney Transplantation and Kidney Diseases, run by EMagnusson at 1 site in United Kingdom.
Trial summary
The advent of new, potent immunosuppressive (anti-rejection) drugs over the past ten years has substantially reduced the risk of rejection after kidney transplantation, has allowed the development of immuno-suppressive regimens that do not use long-term steroids (steroid avoidance), and has improved transplant success… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Kidney Transplantation, Kidney Diseases, Kidney Failure
- What is being tested?
- Campath and Daclizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 123 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Oct 2005to Jun 2011
- Phase
- Phase 4
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Kidney transplant recipients under the care of the West London Renal and Transplant Centre
Who cannot join
- Patients who are unable to give written informed consent
- Simultaneous kidney/pancreas transplant recipients
- Non-heart beating deceased donor transplant recipients
- Patients who would not be offered Campath-1H induction under our current protocol (patients with previous malignancy or with previous exposure to cytotoxic or antiproliferative agents)
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
West London Renal and Transplant Centre, 4th Floor Ham House, Hammersmith Hospital
London, W12 OHS
About this study
Official title: A Randomised Controlled Comparison of Campath-Tacrolimus vs IL2R MoAb-Tacrolimus/Mycophenolate Mofetil in Kidney Transplantation
The advent of new, potent immunosuppressive (anti-rejection) drugs over the past ten years has substantially reduced the risk of rejection after kidney transplantation, has allowed the development of immuno-suppressive regimens that do not use long-term steroids (steroid avoidance), and has improved transplant success rates both in the short and medium term.
The main new agents used in these modern regimens are the calcineurin inhibitor (CNI) tacrolimus; the anti-proliferative agent mycophenolate; and induction agents which are used to provide effective early suppression of the rejection process; these include monoclonal antibodies (MoAb) such as IL-2 receptor blocking antibodies (IL-2R MoAb: basiliximab and daclizumab) and the anti-CD52 antibody Campath-1H (alemtuzumab).
Read more
Although almost all modern immunosuppressive regimens involve one or more of these agents, it is not known which is the safest and most effective combination.
This randomised controlled trial compares two steroid sparing regimens which have been used with very good short and medium term results at St Mary's Hospital Renal and Transplant Unit over the last 5 years. The primary hypothesis is that the alemtuzumab/tacrolimus regimen is as effective and safe as the IL-2R MoAb/tacrolimus/mycophenolate regimen.
Read the detailed description
RECENT EXPERIENCE AT ST MARY'S:
The St Mary's Hospital Renal Unit (now combined with the Hammersmith Hospital Renal Unit at the West London Renal and Transplant Centre) introduced Tacrolimus based immunosuppression in 1995, developing a steroid avoidance regimen based on Tacrolimus, Mycophenolate, and IL-2R MoAb between 2000 and 2002, and moving to Campath-1H as an induction agent in 2004. Results over this period have been excellent with five and ten year survivals with functioning graft rates of 82% and 72% for the first 260 cadaveric kidney transplants performed since 1995.
The two most recent regimens used at St Mary's have both produced very low (< 10%) rejection rates, and very good (> 90%) short-term rejection-free patient and graft survival rates. Between 2002 and 2004, the regimen consisted of induction with an Interleukin-2 (IL2) -Receptor blocking monoclonal antibody with Tacrolimus and Mycophenolate as long term maintenance therapy. In patients without rejection steroid usage was limited to the first 7 days post-transplant. The current regimen uses Campath-1H (which is now well established as an induction agent in renal transplantation for induction), with Tacrolimus monotherapy maintenance and an identical short-course steroid regimen.
CHARACTERISTICS OF THE TWO REGIMENS TO BE COMPARED:
The IL2R MoAb/Tacrolimus/Mycophenolate/Short-course steroids regimen (2002-2004 Regimen 1) has the advantage of flexibility in terms of adjusting maintenance therapy to allow clinical response to patients and transplants with different tolerance of the two maintenance agents, but involves increased expense in terms of using and monitoring the blood levels of two modern (and hence expensive) agents. In addition, patients have long-term exposure to the anti-proliferative agent Mycophenolate, which can be associated with increased risk of infection, gastrointestinal side effects, and skin malignancies.
The Campath-1H/Tacrolimus/Short-course steroids regimen (2004-current, Regimen 2) has the advantage of highly effective immunosuppression in the initial 3-month period, allowing lower doses of the potentially nephrotoxic Tacrolimus to be used, and simplicity, but exposes patients to a period of several months of lymphopenia (reduced lymphocyte counts in the blood) after Campath administration, and reliance on Tacrolimus monotherapy for maintenance which might lead to greater long term Tacrolimus exposure.
PROPOSED STUDY:
In order to allow a proper comparison of these two anti-rejection treatment combinations we propose a randomised trial which will enable us to consider the relative merits of the two regimens without the introduction of bias associated with using historical control groups. Transplant recipients will be randomised in a 1:2 ratio to regimen 1 and regimen 2.
- Conditions
- Kidney Transplantation, Kidney Diseases, Kidney Failure
- Being tested
- Campath, Daclizumab
- Keywords
- Kidney Transplantation, Kidney Disease, Kidney Failure, Graft Rejection
- Medical subject headings
- Kidney Diseases, Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CampathDrug
Also called Alemtuzumab
Monoclonal antibody induction therapy
DaclizumabDrug
Also called Zinbryta
Monoclonal antibody induction therapy
| Study group | Role | What they receive |
|---|---|---|
| Campath-Tacrolimus | Active comparator | Campath induction with 7-day short-course steroids followed by tacrolimus monotherapy Receives: Drug: Campath |
| Daclizumab-Tacrolimus-Mycophenolate | Experimental | Daclizumab induction with 7-day short-course steroids followed by Tacrolimus and Mycophenolate mofetil therapy Receives: Drug: Daclizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
One Year Survival With a Functioning Graft
One year survival with a functioning graft, defined as transplant recipient remaining alive and dialysis-independent. the functioning graft is a graft still functioning at the time of analysis.
Graft function was estimated using the Modification of Diet in Renal Disease four-variable formula and comparison of graft function between arms undertaken with Student'st test.
Measured: 1 year
Secondary outcomes (8)
Occurrence of Rejection Episodes
Biopsy-proven rejection episodes classified using Banff criteria
Measured: 1 year
Occurrence of Significant Episodes of Infection
Occurence of infection of sufficient severity to produce positive cultures or Nucleic-acid test results from blood, urine, or other body fluids
Measured: 1 year
Initial Length of Stay in Hospital
Measured: 1 year
Presence in the Blood of Cells Which Might Trigger Rejection in, or Promote Tolerance to the Graft
Measured: 3 years
Early Development of Scarring in the Grafts
Biopsy proven Calcineurin Inhibitor (CNI) toxicity free survival
Measured: 1 year
Graft Function: Level of Creatinine
Measured: 2 years
Patient Survival Censored for Death With Function
Cumulative patient survival
Measured: 2 years
Graft Survival Censored for Death With Function
Graft survival (defined as grafts maintaining dialysis independence)
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2005 (estimated)
- Study startOct 2005
- Primary completionJun 2011
- Study completionJun 2011
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 (4)Papers the sponsor has linked to this study.
- Other trials for Kidney TransplantationStudies 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 123 participants (actual)
Sponsor and investigators
- Lead sponsor
- EMagnusson
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, EMagnusson, Imperial College Healthcare NHS Trust
- Investigators
- Adam G McLean, FRCP, DPhil, Principal investigator, Hammersmith Hospital NHS TrustDavid H Taube, MBBCh, FRCP, Study director, Hammersmith Hospital NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00246129
- Sponsor's protocol ID
- SMHREN0501
- Other IDs
- 2005-002856-17, 2005
- Status last verified
- Sep 2021
- First submitted
- 28 Oct 2005
- Last updated
- 29 Sep 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Loucaidou M, McLean AG, Cairns TD, Griffith M, Hakim N, Palmer A, Papalois V, Van Tromp J, Loucaides C, Welsh KI, Taube D. Five-year results of kidney transplantation under tacrolimus-based regimes: the persisting significance of vascular rejection. Transplantation. 2003 Oct 15;76(7):1120-3. doi: 10.1097/01.TP.0000076474.76480.A4.
PubMed 14557763Borrows R, Loucaidou M, Van Tromp J, Cairns T, Griffith M, Hakim N, McLean A, Palmer A, Papalois V, Taube D. Steroid sparing with tacrolimus and mycophenolate mofetil in renal transplantation. Am J Transplant. 2004 Nov;4(11):1845-51. doi: 10.1111/j.1600-6143.2004.00583.x.
PubMed 15476485Borrows R, Loucaidou M, Van Tromp J, Singh S, Cairns T, Griffith M, Hakim N, McLean A, Palmer A, Papalois V, Taube D. Steroid sparing in renal transplantation with tacrolimus and mycophenolate mofetil: three-year results. Transplant Proc. 2005 May;37(4):1792-4. doi: 10.1016/j.transproceed.2005.03.150.
PubMed 15919468Chan K, Taube D, Roufosse C, Cook T, Brookes P, Goodall D, Galliford J, Cairns T, Dorling A, Duncan N, Hakim N, Palmer A, Papalois V, Warrens AN, Willicombe M, McLean AG. Kidney transplantation with minimized maintenance: alemtuzumab induction with tacrolimus monotherapy--an open label, randomized trial. Transplantation. 2011 Oct 15;92(7):774-80. doi: 10.1097/TP.0b013e31822ca7ca.
PubMed 21836540
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Controlled Comparison of Campath-Tacrolimus vs IL2R MoAb-Tacrolimus/Mycophenolate Mofetil in Kidney Transplantation
- ClinicalTrials.gov ID
- NCT00246129
- Acronym / sponsor ID
- SMHREN0501
- Conditions
- Kidney Transplantation, Kidney Diseases, Kidney Failure
- Keywords
- Kidney Transplantation, Kidney Disease, Kidney Failure, Graft Rejection
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 123 participants (actual)
- Lead sponsor
- EMagnussonUniversity, hospital or other
- Study start
- Oct 2005 (actual)
- Primary completion
- Jun 2011 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 31 Oct 2005 (estimated)
- Results
- Posted 29 Sep 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The advent of new, potent immunosuppressive (anti-rejection) drugs over the past ten years has substantially reduced the risk of rejection after kidney transplantation, has allowed the development of immuno-suppressive regimens that do not use long-term steroids (steroid avoidance), and has improved transplant success rates both in the short and medium term.
The main new agents used in these modern regimens are the calcineurin inhibitor (CNI) tacrolimus; the anti-proliferative agent mycophenolate; and induction agents which are used to provide effective early suppression of the rejection process; these include monoclonal antibodies (MoAb) such as IL-2 receptor blocking antibodies (IL-2R MoAb: basiliximab and daclizumab) and the anti-CD52 antibody Campath-1H (alemtuzumab).
Although almost all modern immunosuppressive regimens involve one or more of these agents, it is not known which is the safest and most effective combination.
This randomised controlled trial compares two steroid sparing regimens which have been used with very good short and medium term results at St Mary's Hospital Renal and Transplant Unit over the last 5 years. The primary hypothesis is that the alemtuzumab/tacrolimus regimen is as effective and safe as the IL-2R MoAb/tacrolimus/mycophenolate regimen.
Detailed description
RECENT EXPERIENCE AT ST MARY'S:
The St Mary's Hospital Renal Unit (now combined with the Hammersmith Hospital Renal Unit at the West London Renal and Transplant Centre) introduced Tacrolimus based immunosuppression in 1995, developing a steroid avoidance regimen based on Tacrolimus, Mycophenolate, and IL-2R MoAb between 2000 and 2002, and moving to Campath-1H as an induction agent in 2004. Results over this period have been excellent with five and ten year survivals with functioning graft rates of 82% and 72% for the first 260 cadaveric kidney transplants performed since 1995.
The two most recent regimens used at St Mary's have both produced very low (< 10%) rejection rates, and very good (> 90%) short-term rejection-free patient and graft survival rates. Between 2002 and 2004, the regimen consisted of induction with an Interleukin-2 (IL2) -Receptor blocking monoclonal antibody with Tacrolimus and Mycophenolate as long term maintenance therapy. In patients without rejection steroid usage was limited to the first 7 days post-transplant. The current regimen uses Campath-1H (which is now well established as an induction agent in renal transplantation for induction), with Tacrolimus monotherapy maintenance and an identical short-course steroid regimen.
CHARACTERISTICS OF THE TWO REGIMENS TO BE COMPARED:
The IL2R MoAb/Tacrolimus/Mycophenolate/Short-course steroids regimen (2002-2004 Regimen 1) has the advantage of flexibility in terms of adjusting maintenance therapy to allow clinical response to patients and transplants with different tolerance of the two maintenance agents, but involves increased expense in terms of using and monitoring the blood levels of two modern (and hence expensive) agents. In addition, patients have long-term exposure to the anti-proliferative agent Mycophenolate, which can be associated with increased risk of infection, gastrointestinal side effects, and skin malignancies.
The Campath-1H/Tacrolimus/Short-course steroids regimen (2004-current, Regimen 2) has the advantage of highly effective immunosuppression in the initial 3-month period, allowing lower doses of the potentially nephrotoxic Tacrolimus to be used, and simplicity, but exposes patients to a period of several months of lymphopenia (reduced lymphocyte counts in the blood) after Campath administration, and reliance on Tacrolimus monotherapy for maintenance which might lead to greater long term Tacrolimus exposure.
PROPOSED STUDY:
In order to allow a proper comparison of these two anti-rejection treatment combinations we propose a randomised trial which will enable us to consider the relative merits of the two regimens without the introduction of bias associated with using historical control groups. Transplant recipients will be randomised in a 1:2 ratio to regimen 1 and regimen 2.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Campath-Tacrolimus | Active comparator | Drug: CampathCampath induction with 7-day short-course steroids followed by tacrolimus monotherapy |
| Daclizumab-Tacrolimus-Mycophenolate | Experimental | Drug: DaclizumabDaclizumab induction with 7-day short-course steroids followed by Tacrolimus and Mycophenolate mofetil therapy |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Kidney transplant recipients under the care of the West London Renal and Transplant Centre
Key exclusion criteria (4 listed)
- Patients who are unable to give written informed consent
- Simultaneous kidney/pancreas transplant recipients
- Non-heart beating deceased donor transplant recipients
- Patients who would not be offered Campath-1H induction under our current protocol (patients with previous malignancy or with previous exposure to cytotoxic or antiproliferative agents)
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 |
|---|---|---|
| CampathAlso: AlemtuzumabMonoclonal antibody induction therapy | Drug | Campath-Tacrolimus |
| DaclizumabAlso: ZinbrytaMonoclonal antibody induction therapy | Drug | Daclizumab-Tacrolimus-Mycophenolate |
Primary outcome
One Year Survival With a Functioning Graft
Time frame: 1 year
One year survival with a functioning graft, defined as transplant recipient remaining alive and dialysis-independent. the functioning graft is a graft still functioning at the time of analysis. Graft function was estimated using the Modification of Diet in Renal Disease four-variable formula and comparison of graft function between arms undertaken with Student'st test.
8 secondary outcomes
Occurrence of Rejection Episodes
Time frame: 1 year
Occurrence of Significant Episodes of Infection
Time frame: 1 year
Initial Length of Stay in Hospital
Time frame: 1 year
Presence in the Blood of Cells Which Might Trigger Rejection in, or Promote Tolerance to the Graft
Time frame: 3 years
Early Development of Scarring in the Grafts
Time frame: 1 year
Graft Function: Level of Creatinine
Time frame: 2 years
Patient Survival Censored for Death With Function
Time frame: 2 years
Graft Survival Censored for Death With Function
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 14557763Loucaidou M, McLean AG, Cairns TD, Griffith M, Hakim N, Palmer A, Papalois V, Van Tromp J, Loucaides C, Welsh KI, Taube D. Five-year results of kidney transplantation under tacrolimus-based regimes: the persisting significance of vascular rejection. Transplantation. 2003 Oct 15;76(7):1120-3. doi: 10.1097/01.TP.0000076474.76480.A4.
- Background: PubMed 15476485Borrows R, Loucaidou M, Van Tromp J, Cairns T, Griffith M, Hakim N, McLean A, Palmer A, Papalois V, Taube D. Steroid sparing with tacrolimus and mycophenolate mofetil in renal transplantation. Am J Transplant. 2004 Nov;4(11):1845-51. doi: 10.1111/j.1600-6143.2004.00583.x.
- Background: PubMed 15919468Borrows R, Loucaidou M, Van Tromp J, Singh S, Cairns T, Griffith M, Hakim N, McLean A, Palmer A, Papalois V, Taube D. Steroid sparing in renal transplantation with tacrolimus and mycophenolate mofetil: three-year results. Transplant Proc. 2005 May;37(4):1792-4. doi: 10.1016/j.transproceed.2005.03.150.
- Results publication: PubMed 21836540Chan K, Taube D, Roufosse C, Cook T, Brookes P, Goodall D, Galliford J, Cairns T, Dorling A, Duncan N, Hakim N, Palmer A, Papalois V, Warrens AN, Willicombe M, McLean AG. Kidney transplantation with minimized maintenance: alemtuzumab induction with tacrolimus monotherapy--an open label, randomized trial. Transplantation. 2011 Oct 15;92(7):774-80. doi: 10.1097/TP.0b013e31822ca7ca.
- Individual participant dataSharing planned: No
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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.
Adam G McLean, FRCP, DPhil principal investigator
Hammersmith Hospital NHS Trust
David H Taube, MBBCh, FRCP study director
Hammersmith Hospital NHS Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Campath and Daclizumab in people with Kidney Transplantation and Kidney Diseases, run by EMagnusson at 1 site in United Kingdom.
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 1 inclusion and 4 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 29 Sep 2021. 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 Kingdom. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 29 Sep 2021). 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?
One Year Survival With a Functioning Graft (time frame: 1 year). 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 NCT00246129, which also lists 4 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 29 Sep 2021.