Cytomegalovirus InfectionsPhase 4NCT01927588
Evaluation of Early Use of Everolimus (EVE) on Cytomegalovirus (CMV) Infection in Renal Transplant Recipients
A Phase 4 study testing Everolimus+Tacrolimus+Prednisone and Mycophenolate+Tacrolimus+Prednisone in people with Cytomegalovirus Infections, run by Fundação Pró Rim.
Trial summary
CMV infection is common in transplant patients and can cause graft loss. CMV is a major factor in increasing morbidity, and post-transplant costs. The CMV infection is associated with many deleterious indirect effects including rejection, interstitial fibrosis and tubular atrophy, mortality. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Cytomegalovirus Infections
- What is being tested?
- Everolimus+Tacrolimus+Prednisone and Mycophenolate+Tacrolimus+Prednisone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- Aug 2013to Nov 2015
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Primary kidney transplants (living or deceased donors);
Who cannot join
- Recipients of a second transplant;
- Recipients of multiple organs transplants;
- PRA > 50%;
- Chronic liver failure;
- Presence of uncontrolled hypercholesterolemia (≥ 250 mg/dL);
- Or hypertriglyceridemia (≥ 300 mg/dL).
Show all 9Show fewer
- Leucocytes count < 1500 per microliter;
- Platelets count < 75000 per microliter;
- Proteinuria > 800mg/day;
Trial locations and contacts
No sites are listed yet.
About this study
Official title: An Exploratory Evaluation of Early Use of Everolimus (EVE) on Tacrolimus (TAC)-Based Immunosuppressive Regiment vs. Mycophenolate Sodium (MPS) on Cytomegalovirus (CMV) Infection in Renal Transplant Recipients.
CMV infection is common in transplant patients and can cause graft loss. CMV is a major factor in increasing morbidity, and post-transplant costs. The CMV infection is associated with many deleterious indirect effects including rejection, interstitial fibrosis and tubular atrophy, mortality. In addition to the potential for undesirable clinical outcomes associated with CMV, there is also a negative economic aspect. Patients who developed CMV events have been found to use significantly more inpatient and outpatient resources than patients without CMV disease. Universal prophylaxis is associated with high treatment cost and the potential for drug-related toxicity. It can be speculated that use of EVR may offer additional economic benefits in terms of decreased utilization associated with prevention of CMV disease, and reduce use of costly prophylaxis. Any efforts to reduce costs in renal transplants are very important and may have a great impact in total cost of a renal program. And the other hand, the clinical data suggest that EVR is associated with a decrease in CMV incidence compared to mycophenolic acid (MPA). CMV replication is dependent upon 1 ou 2 mTor pathways and in vitro studies support an association between mTor inhibitors and decreased CMV infection and disease. In cardiac transplantation, the use of EVR was associated with a lower incidence of CMV events. Some clinical trials data have also shown that use of EVR was associated with a lower incidence of CMV infection compared to MPA following renal transplantation. Brennan et al compared the incidence of CMV in three clinical trials using EVR versus MPA in De Novo renal transplants. They pooled for analysis the studies B201, B251 and A2309, all double-blind, randomized, parallel-groups that compared the incidence of freedom form and incidence of CMV between EVR groups and MPA groups. The results of this pooled analysis of over 2000 patients de novo renal transplant demonstrated that EVR was associated with a decrease in and delay in the time of onset of CMV events compared to MPA. Our hypothesis is that basiliximab in combination with low dose tacrolimus, everolimus and prednisone may result in comparable efficacy (BCAR) observed in patients receiving tacrolimus/mycophenolate/prednisone but with a better safety profile (CMV infection) and cost-effectiveness.
Read the detailed description
Objectives:
Primary To investigate the effect of early use of EVL plus TAC dose reduced vs. MPS plus TAC full dose on CMV infection by antigenemia 12 month after transplantation in stable kidney transplant recipients.
Secondaries
To evaluate renal function by cGFR (MDRD) To evaluate the incidence of acute rejection and nephrotoxicity by protocol biopsies; To evaluate the incidence of poliomavirus, according to treatment group, by quantitative PCR the BKviremia in urine and biopsy sample.
- Conditions
- Cytomegalovirus Infections
- Being tested
- Everolimus+Tacrolimus+Prednisone, Mycophenolate+Tacrolimus+Prednisone
- Keywords
- Certican, Renal Transplant, Cytomegalovirus Infection
- Medical subject headings
- Cytomegalovirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Everolimus+Tacrolimus+PrednisoneDrug
Also called Certican, Tacrolimus, Prednisone
Certican, introduced at Day7 post transplant + TACreduced + Steroids.
Mycophenolate+Tacrolimus+PrednisoneDrug
Also called Myfortic, Tacrolimus, Prednisone
Myfortic + Tacrolimus full + Steroids, as control arm.
| Study group | Role | What they receive |
|---|---|---|
| Everolimus+Tacrolimus+Prednisone | Experimental | Certican 3mg/daily for 12 months TACreduced 0,15mg/Kg/daily for 12 months Steroids 1mg/Kg/daily for 12 months Receives: Drug: Everolimus+Tacrolimus+Prednisone |
| Mycophenolate+Tacrolimus+Prednisone | Active comparator | Myfortic 720mg twice daily for 12 months TACreduced full dose/Kg/daily for 12 months Steroids 1mg/Kg/daily for 12 months Receives: Drug: Mycophenolate+Tacrolimus+Prednisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cytomegalovirus (CMV) infection investigation
Blood samples will be collected to perform antigenemia at baseline, 1 month, 3 months 6 months and 12 months after transplant to investigate CMV infection.
Measured: one year
Secondary outcomes (3)
Transplant biopsies
At 1, 3, and 12 month, a renal biopsy will be performed. Conventional staining and polyoma virus and CD4d immunohistochemical staining will be done. Methods for immunohistochemical staining procedures will be briefly described: 1. paraffin blocks were deparaffinized in multiple xylene baths, and tissues rehydrated in sequentially graduated ethyl alcohol baths; 2. Sample are predigested in 0.05% protease for 10 min at 37ºC to increase antigenic binding availability; 3.0 after rinsing in Trisbuffered saline, test slides and appropriate positive and negative controls are processed in an automated stainer. Primary antibody NCL-JCBK is applied for 2 hours (or overnight) at 37ºC temperature; then, the secondary antibody (anti-mouse peroxidase antibody) for 30 minutes at 37ºC.
Measured: One year
C4d method
- Tissue will be stained using standard procedures with monoclonal anti-C4d at 1:100 dilution. 2. Secondary anti-mouse FITC-conjungated antibody is applied at a concentration of 1:20; 3. Quantification of staining is recorded, using routine protocols, including pretreatment for 15 min in boiling citrate (pH 8.0), a primary antibody concentration of 1:20 or 1:40 (titered by antibody lot), and secondary goat anti-rabbit IgG antibody at 1:360 dilution. Detection is performed with streptavidin/horseradish peroxidase (Jackson ImmunoResearch) and developed with Stable DAB (Dako, Carpenteria, CA).
Measured: one year
Polyoma identification
Urine samples will be collected to perform Decoy cells research and real time PCR analysis. Q-PCR amplification reactions will be set up in a reaction volume of 50 µl using the TaqMan Universal PCR Master Mix (PE Biosystems), containing 10 µl of purified DNA, 200 and 400 nM of VPf and VPr, and 50 nM of TaqMan probe. Thermal cycling was initiated with a 2-min incubation at 50 °C, followed by a first denaturation step of 10 min at 95 °C and then 40 cycles of 95 °C for 15 s (denaturation) and 60 °C for 1min. Real-time PCR amplification data will be collected continuously and analysed with the Sequence Detection System.
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2013 (estimated)
- Study startAug 2013
- Primary completionNov 2015 (estimated)
- Study completionNov 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cytomegalovirus InfectionsStudies 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
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fundação Pró Rim
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Luciane Mônica Deboni, Fundação Pró Rim
- Investigators
- Luciane M. Deboni, Msc, Principal investigator, Fundação Pró Rim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01927588
- Sponsor's protocol ID
- CRAD001ABR29T
- Other IDs
- CRAD001ABR29T
- Status last verified
- Aug 2013
- First submitted
- 20 Aug 2013
- Last updated
- 22 Aug 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Evaluation of Early Use of Everolimus (EVE) on Tacrolimus (TAC)-Based Immunosuppressive Regiment vs. Mycophenolate Sodium (MPS) on Cytomegalovirus (CMV) Infection in Renal Transplant Recipients.
- ClinicalTrials.gov ID
- NCT01927588
- Acronym / sponsor ID
- CRAD001ABR29T
- Conditions
- Cytomegalovirus Infections
- Keywords
- Certican, Renal Transplant, Cytomegalovirus Infection
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Fundação Pró RimUniversity, hospital or other
- Study start
- Aug 2013
- Primary completion
- Nov 2015 (estimated)
- Study completion
- Nov 2015 (estimated)
- First posted
- 22 Aug 2013 (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.
CMV infection is common in transplant patients and can cause graft loss. CMV is a major factor in increasing morbidity, and post-transplant costs. The CMV infection is associated with many deleterious indirect effects including rejection, interstitial fibrosis and tubular atrophy, mortality. In addition to the potential for undesirable clinical outcomes associated with CMV, there is also a negative economic aspect. Patients who developed CMV events have been found to use significantly more inpatient and outpatient resources than patients without CMV disease. Universal prophylaxis is associated with high treatment cost and the potential for drug-related toxicity. It can be speculated that use of EVR may offer additional economic benefits in terms of decreased utilization associated with prevention of CMV disease, and reduce use of costly prophylaxis. Any efforts to reduce costs in renal transplants are very important and may have a great impact in total cost of a renal program. And the other hand, the clinical data suggest that EVR is associated with a decrease in CMV incidence compared to mycophenolic acid (MPA). CMV replication is dependent upon 1 ou 2 mTor pathways and in vitro studies support an association between mTor inhibitors and decreased CMV infection and disease. In cardiac transplantation, the use of EVR was associated with a lower incidence of CMV events. Some clinical trials data have also shown that use of EVR was associated with a lower incidence of CMV infection compared to MPA following renal transplantation. Brennan et al compared the incidence of CMV in three clinical trials using EVR versus MPA in De Novo renal transplants. They pooled for analysis the studies B201, B251 and A2309, all double-blind, randomized, parallel-groups that compared the incidence of freedom form and incidence of CMV between EVR groups and MPA groups. The results of this pooled analysis of over 2000 patients de novo renal transplant demonstrated that EVR was associated with a decrease in and delay in the time of onset of CMV events compared to MPA. Our hypothesis is that basiliximab in combination with low dose tacrolimus, everolimus and prednisone may result in comparable efficacy (BCAR) observed in patients receiving tacrolimus/mycophenolate/prednisone but with a better safety profile (CMV infection) and cost-effectiveness.
Detailed description
Objectives:
Primary To investigate the effect of early use of EVL plus TAC dose reduced vs. MPS plus TAC full dose on CMV infection by antigenemia 12 month after transplantation in stable kidney transplant recipients.
Secondaries
To evaluate renal function by cGFR (MDRD) To evaluate the incidence of acute rejection and nephrotoxicity by protocol biopsies; To evaluate the incidence of poliomavirus, according to treatment group, by quantitative PCR the BKviremia in urine and biopsy sample.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Everolimus+Tacrolimus+Prednisone | Experimental | Drug: Everolimus+Tacrolimus+PrednisoneCertican 3mg/daily for 12 months TACreduced 0,15mg/Kg/daily for 12 months Steroids 1mg/Kg/daily for 12 months |
| Mycophenolate+Tacrolimus+Prednisone | Active comparator | Drug: Mycophenolate+Tacrolimus+PrednisoneMyfortic 720mg twice daily for 12 months TACreduced full dose/Kg/daily for 12 months Steroids 1mg/Kg/daily for 12 months |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Primary kidney transplants (living or deceased donors);
Key exclusion criteria (9 listed)
- Recipients of a second transplant;
- Recipients of multiple organs transplants;
- PRA > 50%;
- Chronic liver failure;
- Presence of uncontrolled hypercholesterolemia (≥ 250 mg/dL);
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 |
|---|---|---|
| Everolimus+Tacrolimus+PrednisoneAlso: Certican, Tacrolimus, PrednisoneCertican, introduced at Day7 post transplant + TACreduced + Steroids. | Drug | Everolimus+Tacrolimus+Prednisone |
| Mycophenolate+Tacrolimus+PrednisoneAlso: Myfortic, Tacrolimus, PrednisoneMyfortic + Tacrolimus full + Steroids, as control arm. | Drug | Mycophenolate+Tacrolimus+Prednisone |
Primary outcome
Cytomegalovirus (CMV) infection investigation
Time frame: one year
Blood samples will be collected to perform antigenemia at baseline, 1 month, 3 months 6 months and 12 months after transplant to investigate CMV infection.
3 secondary outcomes
Transplant biopsies
Time frame: One year
C4d method
Time frame: one year
Polyoma identification
Time frame: One year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2013.
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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.
Luciane M. Deboni, Msc principal investigator
Fundação Pró Rim
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Everolimus+Tacrolimus+Prednisone and Mycophenolate+Tacrolimus+Prednisone in people with Cytomegalovirus Infections, run by Fundação Pró Rim.
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 9 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: status not confirmed, as of the sponsor's last update on 22 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Luciane M Deboni, Doctor, PI (+55 47 96094320, lmdeboni@terra.com.br), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cytomegalovirus (CMV) infection investigation (time frame: one year). 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 22 Aug 2013.