Campath, Calcineurin inhibitor reduction and Chronic allograft nephropathy
| ISRCTN | ISRCTN88894088 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN88894088 |
| EudraCT/CTIS number | 2008-008553-27 |
| ClinicalTrials.gov number | NCT01120028 |
| Secondary identifying numbers | CTSU3C1 |
- Submission date
- 06/05/2010
- Registration date
- 07/06/2010
- Last edited
- 18/12/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Surgery
Plain English Summary
Background and study aims
In a healthy person, the kidneys are responsible for filtering out the waste products and excess water in the blood, and converting them into urine. If the kidneys suddenly stop working (acute kidney injury) or are suffering from severe, long-term disease of the kidneys (chronic kidney failure) then the body is unable to get rid of the waste products building up in the blood. In some patients, the damage to the kidneys becomes worse over time and so a kidney transplant is their only real option. When a person receives a kidney transplant, they have to take drugs called immunosuppressants, to prevent their immune system rejecting the new kidney (graft). Treatment with these drugs have managed to lower the rate of acute rejection (when the body’s immune system rejects the transplant almost immediately), however the long-term survival of kidney transplants has not really improved over the past decade. The commonest cause of graft loss is a condition called chronic allograft nephropathy (CAN) where the graft itself dies over time due to long-term treatment with calcineurin inhibitors (a type of immunosuppressant medication). They work by stopping the activity of a protein called calcineurin which is involved in activating the certain cells of the immune system. A possible way to prevent this is to lower the amounts of calcineurin patients are taken by replacing them with other medications. This study is going to look at the long-term effects of Campath-1H (an initial immunosuppressant treatment that is not a calcineurin inhibitor) and sirolimus (a maintainance immunosuppressant treatment that is not a calcineurin inhibitor) to the standard treatments of the drugs basiliximab (standard treatment) and tacrolimus (a maintainance immunopsupressent that is a calcineurin inhibitor)
Who can participate?
Adults who are scheduled to receive kidney transplant in next 24 hours
What does the study involve?
Participants are randomly allocated to one of two groups. Those in the first group are treated with two doses of 30mg Campath-1H intravenously (directly into a vein) or subcutaneously (injection into the skin) 24 hours apart as well as taking tacrolimus tablets every day at a dose of 5-7 ng/ml for 6 months. Those in the second group are treated with two doses of 20mg basiliximab intravenously (directly into a vein) spaced four days apart (standard treatment) as well as tacrolimus tablets every day at a dose of 5-12 ng/ml for 6 months. After 6 months, the two groups are randomly allocated to subgroups. From the first group, half of the participants continue taking tacrolimus tablets every day and the other half are given sirolimus tablets to take every day at a dose of 5-10 ng/ml for first 6 months then 5-8 ng/ml. From the second group, half of the particpants continue to take tacrolimus tablets but at a dose of 5-8 ng/ml, and the other half are given sirolimus tablets to take every day at a dose of 5-10 ng/mL for first 6 months, then 5-8 ng/ml. For all groups, study treatments continue (prescribed by the participant's doctor) while their transplant remains functional. All participants are reviewed when they are discharged from hospital and at 1, 3, 6, 9, and 12 months after transplantation, in order to determine the transplant failure rate.
What are the possible benefits and risks of participating?
It is not known as to whether there will be any benefits or risks to those participating in this study.
Where is the study run from?
Oxford Transplant Centre (UK)
When is the study starting and how long is it expected to run for?
September 2010 to August 2017
Who is funding the study?
1. NHS Blood and Transplant Research and Development (UK)
2. Pfizer (UK)
3. Novartis (UK)
Who is the main contact?
Professor Peter Friend
ccc@ndph.ox.ac.uk
Contact information
Scientific
Oxford Transplant Centre
Churchill Hospital
Headington
Oxford
OX3 7LJ
United Kingdom
| Phone | +44 1865 743743 |
|---|---|
| ccc@ndph.ox.ac.uk |
Study information
| Study design | Open label multicentre randomised controlled 2x2 factorial trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details below to request a patient information sheet |
| Scientific title | Open-label, randomised multicentre study of CAMPATH-1H versus basiliximab induction treatment and sirolimus versus tacrolimus maintenance treatment for the preservation of renal function in patients receiving kidney transplants |
| Study acronym | The 3C Study |
| Study hypothesis | Reducing exposure to calcineurin inhibitors either by using more potent antibody induction (Campath) and/or an elective switch to sirolimus-based immunosuppression may improve function and survival of kidney transplants. |
| Ethics approval(s) | Nottingham Research Ethics Committee (REC) 2 approved on the 2nd of December 2009 (ref: 09/H0408/101) |
| Condition | Kidney transplantation |
| Intervention | 1. Campath-1H: 30 mg on days 0 and 1 (intravenously or subcutaneously) 2. Basiliximab 20mg on days 0 and 4 (intravenously) 3. Tacrolimus: oral tablets 3.1. target trough level 8-12 ng/mL following basiliximab induction for first six months 3.2. target trough level 5-7 ng/mL following Campath-1H induction and in all patients after 6 months, for duration of study. 4. Sirolimus: oral tablets; target trough level 5-10 ng/mL for first 6 months then 5-8 ng/mL. For duration of study. The total duration of follow up is at least 5 years for all treatment arms. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Specified |
| Drug / device / biological / vaccine name(s) | Campath-1H, basiliximab, tacrolimus, sirolimus |
| Primary outcome measure | 1. Induction therapy comparison: biopsy-proven acute rejection during the first 6 months after transplantation 2. Maintenance therapy comparison: graft function is measured by estimated glomerular filtration rate at 2 years after transplantation |
| Secondary outcome measures | All secondary outcomes are assessed using a a study-specific questionnaire that has been devised to send to patients and the review of the UK Renal Registry, Hospital Episode Statistics, Office for National Statistics, National Cancer Registry and UK Transplant Registry at 1, 2 and 5 years. 1. Graft function and survival 2. Patient survival 3. Incidence of serious infections 4. Incidence of malignancy 5. Major vascular events |
| Overall study start date | 01/09/2010 |
| Overall study end date | 31/08/2017 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 800 |
| Total final enrolment | 394 |
| Participant inclusion criteria | 1. Men or women aged over 18 years 2. Recipient of kidney transplant from live or deceased donor |
| Participant exclusion criteria | 1. Recipients of multi-organ transplants 2. Previous treatment with Campath-1H 3. Active infection 4. Past history of anaphylaxis to humanized monoclonal antibodies 5. History of malignancy (except for adequately treated non-melanoma skin cancer) 6. Loss of previous transplant within 6 months not due to technical reasons 7. Medical history that might limit the participant's ability to take trial treatments for the duration of the study |
| Recruitment start date | 04/10/2010 |
| Recruitment end date | 21/01/2013 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Old Rd
Headington
Oxford
OX3 7LJ
United Kingdom
Sponsor information
University/education
Ms Heather House
Head of CTRG Team
Joint Research Office
Block 60
Churchill Hospital
Old Road
Headington
Oxford
OX3 7LE
England
United Kingdom
| Phone | +44 (0)1865 270000 |
|---|---|
| heather.house@admin.ox.ac.uk | |
| Website | http://www.admin.ox.ac.uk/rso |
"ROR" |
https://ror.org/052gg0110 |
Funders
Funder type
Government
No information available
Government organisation / For-profit companies (industry)
- Alternative name(s)
- Pfizer Inc., Pfizer Consumer Healthcare, Davis, Charles Pfizer & Company, Warner-Lambert, King Pharmaceuticals, Wyeth Pharmaceuticals, Seagen
- Location
- United States of America
Government organisation / For-profit companies (industry)
- Alternative name(s)
- Novartis AG, Novartis International AG
- Location
- Switzerland
Results and Publications
| Intention to publish date | 31/12/2014 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication of results and maintenance comparison primary outcome results in a peer reviewed journal. |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 08/11/2014 | Yes | No | |
| Results article | results | 01/06/2018 | 18/12/2019 | Yes | No |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
18/12/2019: The following changes have been made:
1. Publication reference added.
2. The total final enrolment number has been added from the reference.
23/12/2016: The address of the sponsor has been updated and the risks and benefits of participating have been added to the plain English summary.
18/02/2016: The recruitment dates have been updated from 01/09/2010 - 31/08/2017 to 04/10/2016 - 31/08/2017. The methods of meaurement used to measure the secondary outcome measures have now also been included. In addition, the Clinical Trial Service Unit at the University of Oxford has been added as a trial participating centre and the study website has been added.
