Renal InsufficiencyPhase 4NCT01312064
De Novo Everolimus-based Therapy for Renal Transplantation Using Rituximab Induction
A Phase 4 study testing rituximab and everolimus and thymoglobulin and tacrolimus in people with Renal Insufficiency, run by National Taiwan University Hospital at 1 site in Taiwan.
Trial summary
The investigators hypothesized that everolimus-based immunosuppressive therapy combined with rituximab induction could provide comparable safety profiles for renal transplant patients, as compared to standard immunosuppressive therapy using thymoglobulin induction, tacrolimus, mycophenolate mofetil and steroids, in… Read more about this study
- Who is it for?
- Ages 15 to 65 years
- Conditions the study is for
- Renal Insufficiency
- What is being tested?
- rituximab and everolimus and thymoglobulin and tacrolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteTaiwan
- Study dates
- Apr 2011to Apr 2012
- 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 15 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male or female patients at 15-65 years of age undergoing renal transplantation
- Patients who have been informed of the potential risks and side effects of the study
- Patients who have given written informed consent to participate in the study
- Females who are not pregnant or nursing women (pregnancy test required)
Who cannot join
- Donor age greater than 65 years
- Patients receiving a perfectly matched kidney (6 matches HLA A, B, DR)
- Patients who are recipients of multiple solid organ transplants
- Patients undergoing second or subsequent transplantation
- Patients with pre-transplant PRA > 30%
- Patients with ABO incompatibility or positive lymphocytotoxicity
Show all 12Show fewer
- Patients with severe, active infection
- Patients who have an abnormal liver profile such as ALT, AST, alkaline phosphatase or total bilirubin >3 times the upper normal limit
- Patient who are HIV-positive or hepatitis C (PCR+ only) B surface antigen positive
- Patients who have been treated with an investigational drug or therapy within one month prior to entry or who will be so treated within 6 months of transplantation
- Patients with a history of malignancy within the last five years except excised squamous or basal cell carcinoma
- Patients with a history of alcohol or drug abuse or signs of alcohol-induced organ damage, mental dysfunction or other factors limiting their ability to comply fully with the study requirements.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Clinical Outcome of de Novo Everolimus-based Immunosuppressive Therapy for Renal Transplantation Using Rituximab Induction
The investigators hypothesized that everolimus-based immunosuppressive therapy combined with rituximab induction could provide comparable safety profiles for renal transplant patients, as compared to standard immunosuppressive therapy using thymoglobulin induction, tacrolimus, mycophenolate mofetil and steroids, in terms of acute rejection rate and renal function.
Rituximab was reported to reverse refractory acute kidney transplant rejection. Combined with immunoadsorption with or without IVIG, rituximab could successfully prevent antibody-mediated rejection in ABO-incompatible renal transplantation. This study is to assess whether a CNI-free regimen including B-cell depleting antibody induction, everolimus and MMF results in comparable long-term function without a negative impact on safety or efficacy of immunosuppression. This study will be open-label and two-arm randomized (2:1).
Read the detailed description
Patients of the study arm (2/3 of the patients) will receive rituximab (375mg/m2) induction and subsequently everolimus-based immunosuppressive therapy. The control arm (1/3 of the patients) will receive thymoglobulin induction and tacrolimus-based immunosuppressive therapy. Everolimus will be given with an initial dose of 1 mg bid within 24 hrs after reperfusion, adjusted to a target trough blood level of 6-10 ng/ml for the first 6 months after transplantation. The control arm (1/3 of the patients) will receive thymoglobulin induction and tacrolimus-based immunosuppressive therapy. The dose of thymoglobulin would be 1.0mg/kg/d for 3 days25. The first dose of thymoglobulin will be administered before graft kidney reperfusion, and so is rituximab. All patients will receive corticosteroid therapy as usual. The initial daily dose of tacrolimus will be 0.15 mg/kg/d given in two doses starting within 24 hours after transplantation. The doses of tacrolimus will be adjusted to target the whole blood trough levels between 8 to 12 ng/ml during the first 30 days after transplantation, and tapered to 6 to 10 ng/ml at 6 months. All patients will receive mycophenolate mofetil (MMF) starting at 2 g/d in divided doses, and then adjusted to maintain WBC between 4000~6000/mm3. All patients entering this study will receive co-trimoxazole as prophylactic medication for at least 12 weeks post-operatively. Valgancyclovir will be given for anti-viral prophylaxis. During the transplant operation, renal biopsy will be performed before vascular perfusion for baseline pathology, and a follow-up biopsy will be scheduled at 2 years after transplantation. The primary endpoint will be incidence of acute rejection, and the secondary endpoints include renal function, graft and patient survival.
Male and female adult patients who are to receive renal transplantation may enter the study. The intention is to enroll 90 patients who have fulfilled inclusion/exclusion criteria into the study. Sixty patients will receive rituximab and everolimus-based therapy, but the other thirty patients will receive thymoglobulin and tacrolimus-based therapy.
- Conditions
- Renal Insufficiency
- Being tested
- rituximab and everolimus, thymoglobulin and tacrolimus
- Keywords
- rituximab, everolimus
- Medical subject headings
- Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rituximab and everolimusDrug
Also called mabthera
rituximab (375mg/m2) induction and subsequently everolimus-based immunosuppressive therapy. Everolimus initial dose: 1 mg bid within 24 hrs after reperfusion, adjusted to a target trough blood level of 6-10 ng/ml for the first 6 months after transplantation.
thymoglobulin and tacrolimusDrug
Also called ATG
thymoglobulin induction and tacrolimus-based immunosuppressive therapy. thymoglobulin dose: 1.0mg/kg/d for 3 days daily dose of tacrolimus: 0.15 mg/kg/d given in two doses starting within 24 hours after transplantation
| Study group | Role | What they receive |
|---|---|---|
| rituximab and everolimus | Active comparator | Patients of the study arm will receive rituximab (375mg/m2) induction and subsequently everolimus-based immunosuppressive therapy. Everolimus will be given with an initial dose of 1 mg bid within 24 hrs after reperfusion, adjusted to a target trough blood level of 6-10 ng/ml for the first 6 months after transplantation. Receives: Drug: rituximab and everolimus |
| thymoglobulin and tacrolimus | Active comparator | The control arm will receive thymoglobulin induction and tacrolimus-based immunosuppressive therapy. The dose of thymoglobulin would be 1.0mg/kg/d for 3 days25. The first dose of thymoglobulin will be administered before graft kidney reperfusion, and so is rituximab. All patients will receive corticosteroid therapy as usual. The initial daily dose of tacrolimus will be 0.15 mg/kg/d given in two doses starting within 24 hours after transplantation. The doses of tacrolimus will be adjusted to target the whole blood trough levels between 8 to 12 ng/ml during the first 30 days after transplantation, and tapered to 6 to 10 ng/ml at 6 months. Receives: Drug: thymoglobulin and tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
acute rejection
The log-rank test will be used to analyse the percentage of rejection-free survival between the two groups. Any patient with a suspicious rejection episode will reveive renal biopsy.
Measured: 6 months
Secondary outcomes (2)
renal function
Renal function will be estimated by Cockcroft-Gault formula and analysed by 2-tailed student test.
Measured: 24 months
adverse event
All adverse events and serious adverse events, infections, and malignancies,will be regular monitored including laboratory variables and vital signs and the performance of physical examinations. Number of participants with adverse events will be compared with Chi-square tests.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2011 (estimated)
- Study startApr 2011
- Primary completionApr 2012
- Study completionApr 2012
Why it stopped: Difficulty collecting
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal InsufficiencyStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- MK Tsai, MD, PhD, Principal investigator, National Taiwan University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01312064
- Sponsor's protocol ID
- 201011050MB
- Status last verified
- Nov 2012
- First submitted
- 26 Jan 2011
- Last updated
- 27 Dec 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Outcome of de Novo Everolimus-based Immunosuppressive Therapy for Renal Transplantation Using Rituximab Induction
- ClinicalTrials.gov ID
- NCT01312064
- Acronym / sponsor ID
- 201011050MB
- Conditions
- Renal Insufficiency
- Keywords
- rituximab, everolimus
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Difficulty collecting
- Enrolment
- 2 participants (actual)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- Apr 2011
- Primary completion
- Apr 2012 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 10 Mar 2011 (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 investigators hypothesized that everolimus-based immunosuppressive therapy combined with rituximab induction could provide comparable safety profiles for renal transplant patients, as compared to standard immunosuppressive therapy using thymoglobulin induction, tacrolimus, mycophenolate mofetil and steroids, in terms of acute rejection rate and renal function.
Rituximab was reported to reverse refractory acute kidney transplant rejection. Combined with immunoadsorption with or without IVIG, rituximab could successfully prevent antibody-mediated rejection in ABO-incompatible renal transplantation. This study is to assess whether a CNI-free regimen including B-cell depleting antibody induction, everolimus and MMF results in comparable long-term function without a negative impact on safety or efficacy of immunosuppression. This study will be open-label and two-arm randomized (2:1).
Detailed description
Patients of the study arm (2/3 of the patients) will receive rituximab (375mg/m2) induction and subsequently everolimus-based immunosuppressive therapy. The control arm (1/3 of the patients) will receive thymoglobulin induction and tacrolimus-based immunosuppressive therapy. Everolimus will be given with an initial dose of 1 mg bid within 24 hrs after reperfusion, adjusted to a target trough blood level of 6-10 ng/ml for the first 6 months after transplantation. The control arm (1/3 of the patients) will receive thymoglobulin induction and tacrolimus-based immunosuppressive therapy. The dose of thymoglobulin would be 1.0mg/kg/d for 3 days25. The first dose of thymoglobulin will be administered before graft kidney reperfusion, and so is rituximab. All patients will receive corticosteroid therapy as usual. The initial daily dose of tacrolimus will be 0.15 mg/kg/d given in two doses starting within 24 hours after transplantation. The doses of tacrolimus will be adjusted to target the whole blood trough levels between 8 to 12 ng/ml during the first 30 days after transplantation, and tapered to 6 to 10 ng/ml at 6 months. All patients will receive mycophenolate mofetil (MMF) starting at 2 g/d in divided doses, and then adjusted to maintain WBC between 4000~6000/mm3. All patients entering this study will receive co-trimoxazole as prophylactic medication for at least 12 weeks post-operatively. Valgancyclovir will be given for anti-viral prophylaxis. During the transplant operation, renal biopsy will be performed before vascular perfusion for baseline pathology, and a follow-up biopsy will be scheduled at 2 years after transplantation. The primary endpoint will be incidence of acute rejection, and the secondary endpoints include renal function, graft and patient survival.
Male and female adult patients who are to receive renal transplantation may enter the study. The intention is to enroll 90 patients who have fulfilled inclusion/exclusion criteria into the study. Sixty patients will receive rituximab and everolimus-based therapy, but the other thirty patients will receive thymoglobulin and tacrolimus-based therapy.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| rituximab and everolimus | Active comparator | Drug: rituximab and everolimusPatients of the study arm will receive rituximab (375mg/m2) induction and subsequently everolimus-based immunosuppressive therapy. Everolimus will be given with an initial dose of 1 mg bid within 24 hrs after reperfusion, adjusted to a target trough blood level of 6-10 ng/ml for the first 6 months after transplantation. |
| thymoglobulin and tacrolimus | Active comparator | Drug: thymoglobulin and tacrolimusThe control arm will receive thymoglobulin induction and tacrolimus-based immunosuppressive therapy. The dose of thymoglobulin would be 1.0mg/kg/d for 3 days25. The first dose of thymoglobulin will be administered before graft kidney reperfusion, and so is rituximab. All patients will receive corticosteroid therapy as usual. The initial daily dose of tacrolimus will be 0.15 mg/kg/d given in two doses starting within 24 hours after transplantation. The doses of tacrolimus will be adjusted to target the whole blood trough levels between 8 to 12 ng/ml during the first 30 days after transplantation, and tapered to 6 to 10 ng/ml at 6 months. |
Who may qualify
- Ages
- 15 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Male or female patients at 15-65 years of age undergoing renal transplantation
- Patients who have been informed of the potential risks and side effects of the study
- Patients who have given written informed consent to participate in the study
- Females who are not pregnant or nursing women (pregnancy test required)
Key exclusion criteria (12 listed)
- Donor age greater than 65 years
- Patients receiving a perfectly matched kidney (6 matches HLA A, B, DR)
- Patients who are recipients of multiple solid organ transplants
- Patients undergoing second or subsequent transplantation
- Patients with pre-transplant PRA > 30%
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 |
|---|---|---|
| rituximab and everolimusAlso: mabtherarituximab (375mg/m2) induction and subsequently everolimus-based immunosuppressive therapy. Everolimus initial dose: 1 mg bid within 24 hrs after reperfusion, adjusted to a target trough blood level of 6-10 ng/ml for the first 6 months after transplantation. | Drug | rituximab and everolimus |
| thymoglobulin and tacrolimusAlso: ATGthymoglobulin induction and tacrolimus-based immunosuppressive therapy. thymoglobulin dose: 1.0mg/kg/d for 3 days daily dose of tacrolimus: 0.15 mg/kg/d given in two doses starting within 24 hours after transplantation | Drug | thymoglobulin and tacrolimus |
Primary outcome
acute rejection
Time frame: 6 months
The log-rank test will be used to analyse the percentage of rejection-free survival between the two groups. Any patient with a suspicious rejection episode will reveive renal biopsy.
2 secondary outcomes
renal function
Time frame: 24 months
adverse event
Time frame: 24 months
Results and safety
The study was stopped early (reason given: Difficulty collecting). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2012.
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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.
MK Tsai, MD, PhD principal investigator
National Taiwan University Hospital
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 rituximab and everolimus and thymoglobulin and tacrolimus in people with Renal Insufficiency, run by National Taiwan University Hospital at 1 site in Taiwan.
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 4 inclusion and 12 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: stopped early, as of the sponsor's last update on 27 Dec 2012. 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 Taiwan. 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 was stopped early (reason given: Difficulty collecting). Results are not available in the source record.
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?
acute rejection (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Dec 2012.