Cytomegalovirus InfectionPhase 4NCT01354301
Efficacy and Safety of Induction Strategies Combined With Low Tacrolimus Exposure in Kidney Transplant Recipients Receiving Everolimus or Sodium Mycophenolate
A Phase 4 study testing Thymoglobulin, Everolimus and Basiliximabe in people with Cytomegalovirus Infection and Renal Transplant Failure, run by Hospital do Rim e Hipertensão at 1 site in Brazil.
Trial summary
Despite the improvement of efficacy results with current immunosuppressive regimens (about 15% of incidence of acute rejection), the security schemes used do not show the same results.The most worldwide used regime is tacrolimus, mycophenolate and prednisone. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cytomegalovirus Infection, Renal Transplant Failure, Transplant; Complication, Rejection
- What is being tested?
- Thymoglobulin, Everolimus and Basiliximabe
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 1 siteBrazil
- Study dates
- May 2011to Dec 2014
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- low risk adult candidates for first renal transplants from living or deceased donors
Who cannot join
- receiving immunosuppressive therapy before transplantation;
- have received an investigational medication within the past 30 days;
- have a known contraindication to the administration of antithymocyte globulin;
- tested positive for human immunodeficiency virus (HIV);
- had had cancer (except nonmelanoma skin cancer) within the previous 2 years;
- Pregnant women, nursing mothers, and women of childbearing potential who will be not using condoms or oral contraceptives will be excluded;
- Patients with any panel reactive antibody (PRA) equal to or above 50%, class I or class II.
Trial locations and contacts
1 site in 1 country.
About this study
Despite the improvement of efficacy results with current immunosuppressive regimens (about 15% of incidence of acute rejection), the security schemes used do not show the same results.The most worldwide used regime is tacrolimus, mycophenolate and prednisone. Despite the favorable efficacy results in our population, the use of this combination is associated with higher incidence of viral infections such as cytomegalovirus, and gastrointestinal events, two common causes of hospital readmissions after renal transplantation at our institution.Given this, the investigators propose a study of our own initiative that attends our local needs: identify the best strategy among the therapeutic options available to maintain the result of current effectiveness and improve the safety profile for kidney transplant recipients.This protocol is a prospective, randomized, single center, designed to compare the safety and efficacy of three immunosuppressive regimens: (1) single dose of antithymocyte globulin, reduced exposure to tacrolimus, everolimus starting on day 2 after transplantation and prednisone; ( 2) basiliximab, reduced exposure to tacrolimus, everolimus starting on day 2 after transplantation and prednisone; (3-control group) basiliximab, reduced exposure to tacrolimus, mycophenolate and prednisone.Our hypothesis is that a single dose of antithymocyte globulin or basiliximab induction therapy in combination with low doses of tacrolimus, everolimus and prednisone results in comparable efficacy observed in patients receiving tacrolimus / mycophenolate / prednisone, but with a better safety profile.
To ensure efficacy, the investigators added to the regimes the induction with monoclonal or polyclonal antibody. To improve the toxicities associated with the current scheme, the investigators replace the use of mycophenolate by everolimus and the investigators reduced the dose of tacrolimus.
Patients will be monitored for blood levels of tacrolimus and everolimus to ensure adequate exposure to immunosuppressive agents.
Read the detailed description
Primary end-point: The incidence of CMV infection or disease during the first year of transplantation.Secondary main end-point: the incidence of treatment failure defined as a composite end-point of BCAR, graft loss, death, loss to follow up.
The investigators anticipate enrolling 300 patients within 12 months. Only low risk adult candidates for first renal transplants from living or deceased donors will be considered for enrollment. Patients will be excluded if they have been receiving immunosuppressive therapy before transplantation; have received an investigational medication within the past 30 days; have a known contraindication to the administration of antithymocyte globulin; if tested positive for human immunodeficiency virus (HIV); if had had cancer (except nonmelanoma skin cancer) within the previous 2 years. Pregnant women, nursing mothers, and women of childbearing potential who will be not using condoms or oral contraceptives will be excluded. Patients with any panel reactive antibody (PRA) equal to or above 50%, class I or class II, will also be excluded. Study visits will be performed at pre transplant, days 0, 1, 7, every week up to month 6 and month 12.
- Being tested
- Thymoglobulin, Everolimus, Basiliximabe, mycophenolate sodium, Tacrolimus
- Keywords
- kidney transplantation, thymoglobulin, everolimus
- Medical subject headings
- Cytomegalovirus Infections, Rejection, Psychology
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ThymoglobulinDrug
intravenously, beginning within the first 24 hours after graft revascularization. Pre-treatment includes hydrocortisone and dipyrone before antithymocyte globulin infusion, which will be reconstituted according to the package insert.
EverolimusDrug
initial 0.75 mg BID dose of everolimus on day 2. Doses will be adjusted from day 5 on to maintain everolimus whole blood trough concentrations between 4-8 ng/ml.
BasiliximabeDrug
days 0 and 4, according to the package insert instructions.
mycophenolate sodiumDrug
720 mg BID. This dose will be reduced according to adverse events.
TacrolimusDrug
0.05 mg/kg BID beginning on day 1. Doses will be adjusted to maintain tacrolimus whole blood trough concentrations between 3-5 ng/ml.
TacrolimusDrug
0.1 mg/kg BID beginning on day 1. Doses will be adjusted to maintain tacrolimus whole blood trough concentrations between 3-8 ng/ml and 3-5 ng/ml after 3 months.
TacrolimusDrug
0.1 mg/kg BID beginning on day 1. Doses will be adjusted to maintain tacrolimus whole blood trough concentrations between 3-8 ng/ml.
| Study group | Role | What they receive |
|---|---|---|
| Thymoglobulin and everolimus | Experimental | single dose antithymocyte globulin, reduced concentration tacrolimus, everolimus starting at day 2 posttransplant and prednisone Receives: Drug: Thymoglobulin; Drug: Everolimus; Drug: Tacrolimus |
| Basiliximabe and everolimus | Experimental | basiliximab, reduced concentration tacrolimus, everolimus starting at day 2 posttransplant and prednisone Receives: Drug: Everolimus; Drug: Basiliximabe; Drug: Tacrolimus |
| Basiliximabe and mycophenolate | Active comparator | basiliximab, reduced concentration tacrolimus, mycophenolate and prednisone. Receives: Drug: Basiliximabe; Drug: mycophenolate sodium; Drug: Tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
incidence of CMV infection or disease
Measured: 1 year
Secondary outcomes (1)
incidence of treatment failure defined as a composite end-point of BCAR, graft loss, death, loss to follow up.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2011 (estimated)
- Study startMay 2011
- Primary completionApr 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cytomegalovirus InfectionStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 300 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital do Rim e Hipertensão
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Helio Tedesco Silva Junior, Hospital do Rim e Hipertensão
- Investigators
- Hélio Tedesco, MD, Principal investigator, Hospital do Rim e Hipertensão - Fundação Oswaldo Ramos
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01354301
- Sponsor's protocol ID
- CRAD001ABR18T
- Status last verified
- Mar 2015
- First submitted
- 13 May 2011
- Last updated
- 23 Mar 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Nunes Ficher K, Dreige Y, Gessolo Lins PR, Nicolau Ferreira A, Toniato de Rezende Freschi J, Linhares K, Stopa Martins S, Custodio L, Cristelli M, Viana L, Wagner Santos D, de Marco R, Gerbase-DeLima M, Proenca H, Aguiar W, Nakamura M, Rosso Felipe C, Medina Pestana J, Tedesco Silva H Jr. Long-term Efficacy and Safety of Everolimus Versus Mycophenolate in Kidney Transplant Recipients Receiving Tacrolimus. Transplantation. 2022 Feb 1;106(2):381-390. doi: 10.1097/TP.0000000000003714.
PubMed 33988338Tedesco-Silva H, Felipe C, Ferreira A, Cristelli M, Oliveira N, Sandes-Freitas T, Aguiar W, Campos E, Gerbase-DeLima M, Franco M, Medina-Pestana J. Reduced Incidence of Cytomegalovirus Infection in Kidney Transplant Recipients Receiving Everolimus and Reduced Tacrolimus Doses. Am J Transplant. 2015 Oct;15(10):2655-64. doi: 10.1111/ajt.13327. Epub 2015 May 18.
PubMed 25988935
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Induction Strategies Combined With Low Tacrolimus Exposure in Kidney Transplant Recipients Receiving Everolimus or Sodium Mycophenolate
- ClinicalTrials.gov ID
- NCT01354301
- Acronym / sponsor ID
- CRAD001ABR18T
- Keywords
- kidney transplantation, thymoglobulin, everolimus
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 300 participants (actual)
- Lead sponsor
- Hospital do Rim e HipertensãoUniversity, hospital or other
- Study start
- May 2011
- Primary completion
- Apr 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 16 May 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.
Despite the improvement of efficacy results with current immunosuppressive regimens (about 15% of incidence of acute rejection), the security schemes used do not show the same results.The most worldwide used regime is tacrolimus, mycophenolate and prednisone. Despite the favorable efficacy results in our population, the use of this combination is associated with higher incidence of viral infections such as cytomegalovirus, and gastrointestinal events, two common causes of hospital readmissions after renal transplantation at our institution.Given this, the investigators propose a study of our own initiative that attends our local needs: identify the best strategy among the therapeutic options available to maintain the result of current effectiveness and improve the safety profile for kidney transplant recipients.This protocol is a prospective, randomized, single center, designed to compare the safety and efficacy of three immunosuppressive regimens: (1) single dose of antithymocyte globulin, reduced exposure to tacrolimus, everolimus starting on day 2 after transplantation and prednisone; ( 2) basiliximab, reduced exposure to tacrolimus, everolimus starting on day 2 after transplantation and prednisone; (3-control group) basiliximab, reduced exposure to tacrolimus, mycophenolate and prednisone.Our hypothesis is that a single dose of antithymocyte globulin or basiliximab induction therapy in combination with low doses of tacrolimus, everolimus and prednisone results in comparable efficacy observed in patients receiving tacrolimus / mycophenolate / prednisone, but with a better safety profile.
To ensure efficacy, the investigators added to the regimes the induction with monoclonal or polyclonal antibody. To improve the toxicities associated with the current scheme, the investigators replace the use of mycophenolate by everolimus and the investigators reduced the dose of tacrolimus.
Patients will be monitored for blood levels of tacrolimus and everolimus to ensure adequate exposure to immunosuppressive agents.
Detailed description
Primary end-point: The incidence of CMV infection or disease during the first year of transplantation.Secondary main end-point: the incidence of treatment failure defined as a composite end-point of BCAR, graft loss, death, loss to follow up.
The investigators anticipate enrolling 300 patients within 12 months. Only low risk adult candidates for first renal transplants from living or deceased donors will be considered for enrollment. Patients will be excluded if they have been receiving immunosuppressive therapy before transplantation; have received an investigational medication within the past 30 days; have a known contraindication to the administration of antithymocyte globulin; if tested positive for human immunodeficiency virus (HIV); if had had cancer (except nonmelanoma skin cancer) within the previous 2 years. Pregnant women, nursing mothers, and women of childbearing potential who will be not using condoms or oral contraceptives will be excluded. Patients with any panel reactive antibody (PRA) equal to or above 50%, class I or class II, will also be excluded. Study visits will be performed at pre transplant, days 0, 1, 7, every week up to month 6 and month 12.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Thymoglobulin and everolimus | Experimental | Drug: Thymoglobulin, Drug: Everolimus, Drug: Tacrolimussingle dose antithymocyte globulin, reduced concentration tacrolimus, everolimus starting at day 2 posttransplant and prednisone |
| Basiliximabe and everolimus | Experimental | Drug: Everolimus, Drug: Basiliximabe, Drug: Tacrolimusbasiliximab, reduced concentration tacrolimus, everolimus starting at day 2 posttransplant and prednisone |
| Basiliximabe and mycophenolate | Active comparator | Drug: Basiliximabe, Drug: mycophenolate sodium, Drug: Tacrolimusbasiliximab, reduced concentration tacrolimus, mycophenolate and prednisone. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- low risk adult candidates for first renal transplants from living or deceased donors
Key exclusion criteria (7 listed)
- receiving immunosuppressive therapy before transplantation;
- have received an investigational medication within the past 30 days;
- have a known contraindication to the administration of antithymocyte globulin;
- tested positive for human immunodeficiency virus (HIV);
- had had cancer (except nonmelanoma skin cancer) within the previous 2 years;
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 |
|---|---|---|
| Thymoglobulinintravenously, beginning within the first 24 hours after graft revascularization. Pre-treatment includes hydrocortisone and dipyrone before antithymocyte globulin infusion, which will be reconstituted according to the package insert. | Drug | Thymoglobulin and everolimus |
| Everolimusinitial 0.75 mg BID dose of everolimus on day 2. Doses will be adjusted from day 5 on to maintain everolimus whole blood trough concentrations between 4-8 ng/ml. | Drug | Basiliximabe and everolimus, Thymoglobulin and everolimus |
| Basiliximabedays 0 and 4, according to the package insert instructions. | Drug | Basiliximabe and everolimus, Basiliximabe and mycophenolate |
| mycophenolate sodium720 mg BID. This dose will be reduced according to adverse events. | Drug | Basiliximabe and mycophenolate |
| Tacrolimus0.05 mg/kg BID beginning on day 1. Doses will be adjusted to maintain tacrolimus whole blood trough concentrations between 3-5 ng/ml. | Drug | Thymoglobulin and everolimus |
| Tacrolimus0.1 mg/kg BID beginning on day 1. Doses will be adjusted to maintain tacrolimus whole blood trough concentrations between 3-8 ng/ml and 3-5 ng/ml after 3 months. | Drug | Basiliximabe and everolimus |
| Tacrolimus0.1 mg/kg BID beginning on day 1. Doses will be adjusted to maintain tacrolimus whole blood trough concentrations between 3-8 ng/ml. | Drug | Basiliximabe and mycophenolate |
Primary outcome
incidence of CMV infection or disease
Time frame: 1 year
1 secondary outcome
incidence of treatment failure defined as a composite end-point of BCAR, graft loss, death, loss to follow up.
Time frame: 1 year
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 23 Mar 2015.
- Derived from this study: PubMed 33988338Nunes Ficher K, Dreige Y, Gessolo Lins PR, Nicolau Ferreira A, Toniato de Rezende Freschi J, Linhares K, Stopa Martins S, Custodio L, Cristelli M, Viana L, Wagner Santos D, de Marco R, Gerbase-DeLima M, Proenca H, Aguiar W, Nakamura M, Rosso Felipe C, Medina Pestana J, Tedesco Silva H Jr. Long-term Efficacy and Safety of Everolimus Versus Mycophenolate in Kidney Transplant Recipients Receiving Tacrolimus. Transplantation. 2022 Feb 1;106(2):381-390. doi: 10.1097/TP.0000000000003714.
- Derived from this study: PubMed 25988935Tedesco-Silva H, Felipe C, Ferreira A, Cristelli M, Oliveira N, Sandes-Freitas T, Aguiar W, Campos E, Gerbase-DeLima M, Franco M, Medina-Pestana J. Reduced Incidence of Cytomegalovirus Infection in Kidney Transplant Recipients Receiving Everolimus and Reduced Tacrolimus Doses. Am J Transplant. 2015 Oct;15(10):2655-64. doi: 10.1111/ajt.13327. Epub 2015 May 18.
Related trials for Cytomegalovirus Infection
RecruitingObservational study
A Study of LIVTENCITY (Maribavir) in Adults With Cytomegalovirus (CMV) Infection After Transplantation in South Korea
Cytomegalovirus (CMV)
RecruitingObservational study
The Natural History of Severe Viral Infections and Characterization of Immune Defects in Patients Without Known Immunocompromise
EBV, HSV
RecruitingPhase 1
TETRAVI Multivirus CTL for Treatment of EBV, CMV, Adenovirus, and BK Infections Post Allogeneic SCT.
Viral Infection
RecruitingPhase 2
CMV CTLs in Neonates With CMV Infection
Congenital Cytomegaloviral (CMV) Disease
RecruitingPhase 2
CMV-MVA Triplex Vaccination in HLA-Matched Related Stem Cell Donors for the Prevention of CMV Infection in Patients Undergoing Hematopoietic Stem Cell Transplant
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia
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.
Hélio Tedesco, MD principal investigator
Hospital do Rim e Hipertensão - Fundação Oswaldo Ramos
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 Thymoglobulin, Everolimus and Basiliximabe in people with Cytomegalovirus Infection and Renal Transplant Failure, run by Hospital do Rim e Hipertensão at 1 site in Brazil.
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 7 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 23 Mar 2015. 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 Brazil. 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?
incidence of CMV infection or disease (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 NCT01354301, 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 23 Mar 2015.