Disorder Related to Renal TransplantationPhase 4SIRESNCT01195194
Selection of Immunosuppression in Kidney Transplant Recipients Depending on Pre-transplant Donor-specific T-cell Reactivity.
A Phase 4 study testing PRE-TRANSPLANT (PRE=before) in people with Disorder Related to Renal Transplantation, run by Josep M Grinyo at 2 sites in Spain.
Trial summary
The objective is to assess if low pre-transplantation donor specific T-cell reactive patients measured by Enzyme-linked immunosorbent spot (ELISPOT)assay can be safely managed with Calcineurin inhibitor(CNI)-free Sirolimus(SRL)-based immunosuppression. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Disorder Related to Renal Transplantation
- What is being tested?
- PRE-TRANSPLANT (PRE=before)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 61 participants
- Where
- 2 sitesSpain
- Study dates
- Mar 2008to Jun 2013
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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
- Age of donor and recipient between 18 and 65 years.
- End-stage renal disease and scheduled to receive a primary or secondary renal allograft from a cadaveric, a living-unrelated, or a living-related donor. Patients scheduled for a second transplant must have maintained their primary graft for at least 6 months after transplantation, with the exception of graft failure due to technical reasons.
- Panel reactive antibody (PRA) ≤ 20%, with negative standard cross-match.
- Women of childbearing potential must have a negative serum pregnancy test before randomization.
- Women of childbearing potential must agree to use a medically acceptable method of contraception throughout the treatment period and for 3 months following discontinuation of assigned treatment.
- Signed and dated informed consent prior to transplantation.
Who cannot join
- Multiple organ transplants
- Recipients of adult or pediatric en bloc kidney transplants or dual transplantation or non-heart beating donors.
- Evidence of active systemic or localized major infection.
- Evidence of infiltrate, cavitation, or consolidation on chest x-ray obtained during the screening/baseline evaluation.
- Use of any investigational drug or treatment up to 4 weeks prior to transplantation.
- Treatment with voriconazole, ketoconazole, itraconazole, fluconazole, clotrimazole, astemizole, pimozide, terfenadine, erythromycin, clarithromycin, telithromycin, troleandomycin, rifampin, rifabutin, or St. John's Wort that is not discontinued prior to randomization.
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- Treatment with aminoglycosides, amphotericin B, cisplatin, cisapride, metoclopramide, cimetidine, bromocriptine, danazol, or other drugs associated with renal dysfunction that are not discontinued prior to randomization.
- Subjects with a screening/baseline total white blood cell count < 2,000/mm3 or absolute neutrophil count (ANC) < 500, platelet count < 100,000/mm3.
- Fasting triglycerides > 400 mg/dL (> 4.6 mmol/L) or fasting total cholesterol > 300 mg/dL (> 7.8 mmol/L) despite optimal lipid-lowering therapy.
- History of malignancy within 2 years of enrollment (except for adequately treated basal cell or squamous cell carcinoma of the skin).
- Auto-immune diseases inactive immunosuppressive treatment ( 3 months prior to inclusion).
- Patient with psychiatric disorders that could be non-compliance for the treatment.
- Non Caucasian patients.
- Active peptic ulcers that could produce intestinal absorption disorders.
- Subjects who are known to be human immunodeficiency virus(HIV) or hepatitis B virus (HBV) positive. Patients with hepatitis C virus (HCV) positive should be excluded if polymerase chain reaction (PCR) positive or transaminates values are ≥2 upper normal value (UNV).
- Diabetic patients.
- Body mass index higher than 30 Kg/m2.
Trial locations and contacts
2 sites in 1 country.
Spain2 sites
Nephrology Department. Hospital Vall d'Hebró
Barcelona, Barcelona, 08035
Nephrology Department. Hospital de Bellvitge
L'Hospitalet de Llobregat, Barcelone, 08907
About this study
Official title: Pilot Study of Selection of Either Calcineurin Inhibitor(CNI)-Based or CNI-free Immunosuppressive Regimen Depending on the Result of Pre-transplantation Donor-specific T-cell Reactivity Measured by Enzyme-linked Immunosorbent Spot(ELISPOT) in Standard-risk Kidney Recipients.
The objective is to assess if low pre-transplantation donor specific T-cell reactive patients measured by Enzyme-linked immunosorbent spot (ELISPOT)assay can be safely managed with Calcineurin inhibitor(CNI)-free Sirolimus(SRL)-based immunosuppression.
Read the detailed description
Non randomized, pilot, prospective, open-label trial.
- Being tested
- PRE-TRANSPLANT (PRE=before)
- Keywords
- T-cell lymphocyte allo-recognition, CNI-free immunosuppressive regimen, Enzyme-linked immunospot (ELISPOT)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PRE-TRANSPLANT (PRE=before)Drug
All patients will start with Thymoglobulin 1 mg/kg before transplant followed by 0,5 mg/kg/d during the next 5 days (total accumulated 3,5 mg/kg).
Steroids will be administered at 0,25 mg/kg/d until month 3rd, followed by 0,1 mg/kg/d thereafter.
Mycophenolate Mofetil: Pre-transplant 2 grams iv. After transplantation 1g/12 hours, starting iv and changing to oral formulation as soon as patient starts with oral intake (targeting mycophenolic acid (MPA) C0h levels 2-5 µg/mL).
| Study group | Role | What they receive |
|---|---|---|
| A- negative pre-transplant ELISPOT | Experimental | Sirolimus: Start at 5 mg/day as soon as treatment allocation arrives to obtain targeting levels to 8 -15 ng/ml (immunoassay) in the first 3 months, followed by trough levels of 5-10 ng/ml. Receives: Drug: PRE-TRANSPLANT (PRE=before) |
| B- Positive pre-transplant ELISPOT | Experimental | Tacrolimus 0.1 mg/kg/12h starting as soon as treatment allocation arrives to obtain targeting troughs levels of 8-15 ng/ml the first 3 months, followed by trough levels of 5-10 ng/ml until the end of the study. Receives: Drug: PRE-TRANSPLANT (PRE=before) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of biopsy-confirmed acute rejection episodes
To describe cumulative biopsy-confirmed acute rejection in both groups by intention to treat analysis.
Measured: 6 months
Secondary outcomes (13)
Percentage of steroid-sensitive acute rejection episodes
To describe the percentage of steroid-sensitive acute rejections rejection in both groups by intention to treat analysis.
Measured: 6 months
Percentage of acute rejection episodes requiring treatment with antilymphocyte antibodies.
To describe the need for antibody treatment in acute rejection episodes in both groups by intention to treat analysis.
Measured: 6 months
Renal function estimated by Modification of Diet in Renal Disease (MDRD) formula.
To describe renal function measured by MDRD in both groups by intention to treat and "on therapy" analysis.
Measured: 12 months
Proteinuria measured in g/day
To describe proteinuria in g/day in both groups by intention to treat analysis.
Measured: 6 months
Histology at month 6 protocol kidney allograft biopsy
To describe histology at month 6 in both groups by intention to treat and "on therapy" analysis.
Measured: 6 months
Percentage of patients with negative ELISPOT
To describe percentage of patients with negative ELISPOT in both groups by intention to treat and "on therapy" analysis.
Measured: 6 months
Percentage of patients in group A requiring CNI introduction.
To describe the percentage of patients in group A requiring CNI introduction.
Measured: 24 months
Percentage of patients presenting adverse events requiring study withdrawal
To describe adverse events in the whole group ("screening failure" plus "intention to treat") in both treatments groups.
Measured: 24 months
Percentage of biopsy-confirmed acute rejection episodes
To describe cumulative biopsy-confirmed acute rejection in both groups by intention to treat analysis.
Measured: 12 months
Percentage of steroid-sensitive acute rejections rejection episodes
To describe the percentage of steroid-sensitive acute rejections rejection in both groups by intention to treat analysis.
Measured: 12 months
Percentage of acute rejection episodes requiring treatment with antilymphocyte antibodies
To describe the need for antibody treatment in acute rejection episodes in both groups by intention to treat analysis.
Measured: 12 months
Proteinuria measured in g/day
To describe proteinuria in g/day in both groups by intention to treat analysis.
Measured: 12 months
Percentage of patients with negative ELISPOT
To describe percentage of patients with negative ELISPOT in both groups by intention to treat and "on therapy" analysis.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Sep 2010 (estimated)
- Study startMar 2008
- Primary completionJun 2012
- Study completionJun 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Disorder Related to Renal 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
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- Josep M Grinyo
- Sponsor type
- University, hospital or other
- Collaborators
- Carlos III Health Institute
- Responsible party
- Sponsor-investigator, Josep M Grinyo, Hospital Universitari de Bellvitge
- Investigators
- Josep M Grinyó, PhD MD, Principal investigator, Nephrology Department. Hospital de Bellvitge. Spain
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01195194
- Sponsor's protocol ID
- SIRES
- Other IDs
- 2007-002378-68
- Acronym
- SIRES
- Status last verified
- Feb 2014
- First submitted
- 19 Apr 2010
- Last updated
- 25 Feb 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Bestard O, Cruzado JM, Mestre M, Caldes A, Bas J, Carrera M, Torras J, Rama I, Moreso F, Seron D, Grinyo JM. Achieving donor-specific hyporesponsiveness is associated with FOXP3+ regulatory T cell recruitment in human renal allograft infiltrates. J Immunol. 2007 Oct 1;179(7):4901-9. doi: 10.4049/jimmunol.179.7.4901.
PubMed 17878390Bestard O, Crespo E, Stein M, Lucia M, Roelen DL, de Vaal YJ, Hernandez-Fuentes MP, Chatenoud L, Wood KJ, Claas FH, Cruzado JM, Grinyo JM, Volk HD, Reinke P. Cross-validation of IFN-gamma Elispot assay for measuring alloreactive memory/effector T cell responses in renal transplant recipients. Am J Transplant. 2013 Jul;13(7):1880-90. doi: 10.1111/ajt.12285. Epub 2013 Jun 13.
PubMed 23763435Bestard O, Cruzado JM, Lucia M, Crespo E, Casis L, Sawitzki B, Vogt K, Cantarell C, Torras J, Melilli E, Mast R, Martinez-Castelao A, Goma M, Reinke P, Volk HD, Grinyo JM. Prospective assessment of antidonor cellular alloreactivity is a tool for guidance of immunosuppression in kidney transplantation. Kidney Int. 2013 Dec;84(6):1226-36. doi: 10.1038/ki.2013.236. Epub 2013 Jun 19.
PubMed 23783240
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Selection of Either Calcineurin Inhibitor(CNI)-Based or CNI-free Immunosuppressive Regimen Depending on the Result of Pre-transplantation Donor-specific T-cell Reactivity Measured by Enzyme-linked Immunosorbent Spot(ELISPOT) in Standard-risk Kidney Recipients.
- ClinicalTrials.gov ID
- NCT01195194
- Acronym / sponsor ID
- SIRES / SIRES
- Keywords
- T-cell lymphocyte allo-recognition, CNI-free immunosuppressive regimen, Enzyme-linked immunospot (ELISPOT)
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- Josep M GrinyoUniversity, hospital or other
- Collaborators
- Carlos III Health Institute
- Study start
- Mar 2008
- Primary completion
- Jun 2012 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 6 Sep 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective is to assess if low pre-transplantation donor specific T-cell reactive patients measured by Enzyme-linked immunosorbent spot (ELISPOT)assay can be safely managed with Calcineurin inhibitor(CNI)-free Sirolimus(SRL)-based immunosuppression.
Detailed description
Non randomized, pilot, prospective, open-label trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A- negative pre-transplant ELISPOT | Experimental | Drug: PRE-TRANSPLANT (PRE=before)Sirolimus: Start at 5 mg/day as soon as treatment allocation arrives to obtain targeting levels to 8 -15 ng/ml (immunoassay) in the first 3 months, followed by trough levels of 5-10 ng/ml. |
| B- Positive pre-transplant ELISPOT | Experimental | Drug: PRE-TRANSPLANT (PRE=before)Tacrolimus 0.1 mg/kg/12h starting as soon as treatment allocation arrives to obtain targeting troughs levels of 8-15 ng/ml the first 3 months, followed by trough levels of 5-10 ng/ml until the end of the study. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age of donor and recipient between 18 and 65 years.
- End-stage renal disease and scheduled to receive a primary or secondary renal allograft from a cadaveric, a living-unrelated, or a living-related donor. Patients scheduled for a second transplant must have maintained their primary graft for at least 6 months after transplantation, with the exception of graft failure due to technical reasons.
- Panel reactive antibody (PRA) ≤ 20%, with negative standard cross-match.
- Women of childbearing potential must have a negative serum pregnancy test before randomization.
- Women of childbearing potential must agree to use a medically acceptable method of contraception throughout the treatment period and for 3 months following discontinuation of assigned treatment.
Key exclusion criteria (17 listed)
- Multiple organ transplants
- Recipients of adult or pediatric en bloc kidney transplants or dual transplantation or non-heart beating donors.
- Evidence of active systemic or localized major infection.
- Evidence of infiltrate, cavitation, or consolidation on chest x-ray obtained during the screening/baseline evaluation.
- Use of any investigational drug or treatment up to 4 weeks prior to transplantation.
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 |
|---|---|---|
| PRE-TRANSPLANT (PRE=before)All patients will start with Thymoglobulin 1 mg/kg before transplant followed by 0,5 mg/kg/d during the next 5 days (total accumulated 3,5 mg/kg). Steroids will be administered at 0,25 mg/kg/d until month 3rd, followed by 0,1 mg/kg/d thereafter. Mycophenolate Mofetil: Pre-transplant 2 grams iv. After transplantation 1g/12 hours, starting iv and changing to oral formulation as soon as patient starts with oral intake (targeting mycophenolic acid (MPA) C0h levels 2-5 µg/mL). | Drug | A- negative pre-transplant ELISPOT, B- Positive pre-transplant ELISPOT |
Primary outcome
Percentage of biopsy-confirmed acute rejection episodes
Time frame: 6 months
To describe cumulative biopsy-confirmed acute rejection in both groups by intention to treat analysis.
13 secondary outcomes
Percentage of steroid-sensitive acute rejection episodes
Time frame: 6 months
Percentage of acute rejection episodes requiring treatment with antilymphocyte antibodies.
Time frame: 6 months
Renal function estimated by Modification of Diet in Renal Disease (MDRD) formula.
Time frame: 12 months
Proteinuria measured in g/day
Time frame: 6 months
Histology at month 6 protocol kidney allograft biopsy
Time frame: 6 months
Percentage of patients with negative ELISPOT
Time frame: 6 months
Percentage of patients in group A requiring CNI introduction.
Time frame: 24 months
Percentage of patients presenting adverse events requiring study withdrawal
Time frame: 24 months
Percentage of biopsy-confirmed acute rejection episodes
Time frame: 12 months
Percentage of steroid-sensitive acute rejections rejection episodes
Time frame: 12 months
Percentage of acute rejection episodes requiring treatment with antilymphocyte antibodies
Time frame: 12 months
Proteinuria measured in g/day
Time frame: 12 months
Percentage of patients with negative ELISPOT
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2014.
- Background: PubMed 17878390Bestard O, Cruzado JM, Mestre M, Caldes A, Bas J, Carrera M, Torras J, Rama I, Moreso F, Seron D, Grinyo JM. Achieving donor-specific hyporesponsiveness is associated with FOXP3+ regulatory T cell recruitment in human renal allograft infiltrates. J Immunol. 2007 Oct 1;179(7):4901-9. doi: 10.4049/jimmunol.179.7.4901.
- Background: PubMed 23763435Bestard O, Crespo E, Stein M, Lucia M, Roelen DL, de Vaal YJ, Hernandez-Fuentes MP, Chatenoud L, Wood KJ, Claas FH, Cruzado JM, Grinyo JM, Volk HD, Reinke P. Cross-validation of IFN-gamma Elispot assay for measuring alloreactive memory/effector T cell responses in renal transplant recipients. Am J Transplant. 2013 Jul;13(7):1880-90. doi: 10.1111/ajt.12285. Epub 2013 Jun 13.
- Results publication: PubMed 23783240Bestard O, Cruzado JM, Lucia M, Crespo E, Casis L, Sawitzki B, Vogt K, Cantarell C, Torras J, Melilli E, Mast R, Martinez-Castelao A, Goma M, Reinke P, Volk HD, Grinyo JM. Prospective assessment of antidonor cellular alloreactivity is a tool for guidance of immunosuppression in kidney transplantation. Kidney Int. 2013 Dec;84(6):1226-36. doi: 10.1038/ki.2013.236. Epub 2013 Jun 19.
- This is the center in Spain for the central contact and the main location including patients.Link provided by the sponsor.
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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.
Josep M Grinyó, PhD MD principal investigator
Nephrology Department. Hospital de Bellvitge. Spain
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing PRE-TRANSPLANT (PRE=before) in people with Disorder Related to Renal Transplantation, run by Josep M Grinyo at 2 sites in Spain.
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 17 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 25 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Spain. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Percentage of biopsy-confirmed acute rejection episodes (time frame: 6 months). 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 NCT01195194, 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 25 Feb 2014.