Highly-sensitized Kidney Transplant RecipientsPhase 2NCT01911546
Role of Everolimus in Highly Sensitized Patients
A Phase 2 study testing everolimus + low-dose tacrolimus in people with Highly-sensitized Kidney Transplant Recipients, run by Joseph Kahwaji, MD, MPH at 1 site in United States.
Trial summary
A growing number of patients on the kidney transplant waiting list are broadly human leukocyte antigen (HLA) sensitized (HS). These patients are unlikely to have a compatible donor. Therefore they wait longer and have increased morbidity and mortality. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Highly-sensitized Kidney Transplant Recipients
- What is being tested?
- everolimus + low-dose tacrolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2013to 19 Jan 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Recipient of a deceased or living donor kidney allograft
- Patients must have undergone desensitization with IVIG and rituximab with or without plasma exchange prior to transplant or be administered IVIG and rituximab peri-operatively.
- Age 18 and over
- Able to understand and provide informed consent
Who cannot join
- Recipients of a dual simultaneous kidney/liver, kidney/heart, kidney/lung transplant 2. Pregnant or lactating females 3. Patients with a platelet count < 100,000/mm3 at time of randomization 4. Patients with an absolute neutrophil count < 1,500/mm3 or a white blood cell count of <3,000/mm3 at time of randomization 5. Patients who have an abnormal liver profile such as ALT, AST, Alkaline Phosphatase, or total bilirubin > 3 times the upper limit of normal (ULN) at time of randomization 6. Patients with severe total hypercholesterolemia (> 350 mg/dL; > 9 mmol/L) or total hypertriglyceridemia (> 500 mg/dL; > 5.6 mmol/L). Patients on lipid lowering treatment with controlled hyperlipidemia are acceptable.
- 7. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes 8. Patients being treated with drugs that are strong inducers or inhibitors of cytochrome P450 3A4 9. Patients with a clinically significant systemic infection within 30 days prior to transplant 9 10. Patients who have any surgical or medical condition, such as severe diarrhea, active peptic ulcer disease, or uncontrolled diabetes mellitus, which in the opinion of the investigator, might significantly alter the absorption, distribution, metabolism and/or excretion of study medication.
- 11. Patients with a history of coagulopathy or medical condition that would require long-term anticoagulation therapy after transplantation, unless the condition would permit a two week interruption in therapy before and after allograft biopsy. (Treatment with low dose aspirin is allowed.) 12. Women of childbearing potential who are either pregnant, lactating, planning to become pregnant during this trial, or with a positive serum or urine pregnancy test. Women of childbearing potential must be willing to agree to contraceptive practices.
Trial locations and contacts
1 site in 1 country.
United States1 site
Cedars-Sinai Medical Center
Los Angeles, California, 90048
About this study
Official title: A Prospective, Pilot Trial to Evaluate Safety and Tolerability of Everolimus for the Prevention of BK and CMV Viremia in HLA Sensitized Kidney Transplant Recipients
A growing number of patients on the kidney transplant waiting list are broadly human leukocyte antigen (HLA) sensitized (HS). These patients are unlikely to have a compatible donor. Therefore they wait longer and have increased morbidity and mortality. Desensitization with intravenous immune globulin (IVIG) and rituximab with alemtuzumab induction improves transplant rates and achieves good allograft outcomes. However, HS patients are at risk for viral infections after transplant. We have previously shown an increased incidence of BKV infections after desensitization with HS patients having higher peak viral loads. Cytomegalovirus (CMV) and polyomavirus BK (BKV) infections place HS renal transplant recipients at particular risk. Allograft rejection is associated with both CMV and BKV infection. This is of particular concern for HS patients as they are at an increased risk of rejection at baseline. Furthermore, the frequent development of leukopenia after transplantation often requires the CMV prophylactic agent to be discontinued along with lowering immunosuppression. This increases the risk of CMV infection and allograft rejection.
Everolimus was approved for rejection prophylaxis in combination with calcineurin inhibitors (CNI). CNI used in the study that led to drug's approval was cyclosporine. There are several trials nearing it's completion that utilize low dose tacrolimus instead. In 2012 Novartis published data from several trials showing superior outcomes using everolimus + low dose tacrolimus. This combination is currently approved in EU. It is also a combination that is standard of care (SOC) at our center for patients on everolimus.
This study aims to demonstrate that use of everolimus as part of a maintenance immunosuppression regimen may decrease viral infections without lowering overall immunosuppression thus improving allograft function and survival.
- Being tested
- everolimus + low-dose tacrolimus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
everolimus + low-dose tacrolimusDrug
Also called zortress + prograf
Patients are supplied everolimus (Zortress) + prograf
| Study group | Role | What they receive |
|---|---|---|
| everolimus + low-dose tacrolimus | Experimental | Patients receiving everolimus will be on low dose tacrolimus. Receives: Drug: everolimus + low-dose tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Number of Polyoma BK Viremia Patients
Patients will be monitored at regular interval for the development of Polyomavirus Viremia.
Measured: 12 months
The Number of CMV Viremia
The number of patients with CMV viremia
Measured: 12 Months
Incidence of Antibody Mediated Rejection (ABMR)
Protocol biopsies were obtained at T0 and 6 months post transplant.
Measured: 6 months
Secondary outcomes (1)
Incidence of Cell Mediated Rejection (CMR)
Patients will be monitored for any episodes of CMR.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2013 (estimated)
- Study startJun 2013
- Primary completionJan 2016
- Study completion19 Jan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Highly-sensitized Kidney Transplant RecipientsStudies 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 2
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Joseph Kahwaji, MD, MPH
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor-investigator, Joseph Kahwaji, MD, MPH, Cedars-Sinai Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01911546
- Sponsor's protocol ID
- CRAD001AUS200T
- Status last verified
- Nov 2017
- First submitted
- 4 Mar 2013
- Last updated
- 7 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Pilot Trial to Evaluate Safety and Tolerability of Everolimus for the Prevention of BK and CMV Viremia in HLA Sensitized Kidney Transplant Recipients
- ClinicalTrials.gov ID
- NCT01911546
- Acronym / sponsor ID
- CRAD001AUS200T
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Joseph Kahwaji, MD, MPHUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Jun 2013
- Primary completion
- Jan 2016 (actual)
- Study completion
- 19 Jan 2016 (actual)
- First posted
- 30 Jul 2013 (estimated)
- Results
- Posted 7 Dec 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A growing number of patients on the kidney transplant waiting list are broadly human leukocyte antigen (HLA) sensitized (HS). These patients are unlikely to have a compatible donor. Therefore they wait longer and have increased morbidity and mortality. Desensitization with intravenous immune globulin (IVIG) and rituximab with alemtuzumab induction improves transplant rates and achieves good allograft outcomes. However, HS patients are at risk for viral infections after transplant. We have previously shown an increased incidence of BKV infections after desensitization with HS patients having higher peak viral loads. Cytomegalovirus (CMV) and polyomavirus BK (BKV) infections place HS renal transplant recipients at particular risk. Allograft rejection is associated with both CMV and BKV infection. This is of particular concern for HS patients as they are at an increased risk of rejection at baseline. Furthermore, the frequent development of leukopenia after transplantation often requires the CMV prophylactic agent to be discontinued along with lowering immunosuppression. This increases the risk of CMV infection and allograft rejection.
Everolimus was approved for rejection prophylaxis in combination with calcineurin inhibitors (CNI). CNI used in the study that led to drug's approval was cyclosporine. There are several trials nearing it's completion that utilize low dose tacrolimus instead. In 2012 Novartis published data from several trials showing superior outcomes using everolimus + low dose tacrolimus. This combination is currently approved in EU. It is also a combination that is standard of care (SOC) at our center for patients on everolimus.
This study aims to demonstrate that use of everolimus as part of a maintenance immunosuppression regimen may decrease viral infections without lowering overall immunosuppression thus improving allograft function and survival.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| everolimus + low-dose tacrolimus | Experimental | Drug: everolimus + low-dose tacrolimusPatients receiving everolimus will be on low dose tacrolimus. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Recipient of a deceased or living donor kidney allograft
- Patients must have undergone desensitization with IVIG and rituximab with or without plasma exchange prior to transplant or be administered IVIG and rituximab peri-operatively.
- Age 18 and over
- Able to understand and provide informed consent
Key exclusion criteria (3 listed)
- Recipients of a dual simultaneous kidney/liver, kidney/heart, kidney/lung transplant 2. Pregnant or lactating females 3. Patients with a platelet count < 100,000/mm3 at time of randomization 4. Patients with an absolute neutrophil count < 1,500/mm3 or a white blood cell count of <3,000/mm3 at time of randomization 5. Patients who have an abnormal liver profile such as ALT, AST, Alkaline Phosphatase, or total bilirubin > 3 times the upper limit of normal (ULN) at time of randomization 6. Patients with severe total hypercholesterolemia (> 350 mg/dL; > 9 mmol/L) or total hypertriglyceridemia (> 500 mg/dL; > 5.6 mmol/L). Patients on lipid lowering treatment with controlled hyperlipidemia are acceptable.
- 7. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes 8. Patients being treated with drugs that are strong inducers or inhibitors of cytochrome P450 3A4 9. Patients with a clinically significant systemic infection within 30 days prior to transplant 9 10. Patients who have any surgical or medical condition, such as severe diarrhea, active peptic ulcer disease, or uncontrolled diabetes mellitus, which in the opinion of the investigator, might significantly alter the absorption, distribution, metabolism and/or excretion of study medication.
- 11. Patients with a history of coagulopathy or medical condition that would require long-term anticoagulation therapy after transplantation, unless the condition would permit a two week interruption in therapy before and after allograft biopsy. (Treatment with low dose aspirin is allowed.) 12. Women of childbearing potential who are either pregnant, lactating, planning to become pregnant during this trial, or with a positive serum or urine pregnancy test. Women of childbearing potential must be willing to agree to contraceptive practices.
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 + low-dose tacrolimusAlso: zortress + prografPatients are supplied everolimus (Zortress) + prograf | Drug | everolimus + low-dose tacrolimus |
Primary outcome
The Number of Polyoma BK Viremia Patients
Time frame: 12 months
Patients will be monitored at regular interval for the development of Polyomavirus Viremia.
The Number of CMV Viremia
Time frame: 12 Months
The number of patients with CMV viremia
Incidence of Antibody Mediated Rejection (ABMR)
Time frame: 6 months
Protocol biopsies were obtained at T0 and 6 months post transplant.
1 secondary outcome
Incidence of Cell Mediated Rejection (CMR)
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing everolimus + low-dose tacrolimus in people with Highly-sensitized Kidney Transplant Recipients, run by Joseph Kahwaji, MD, MPH at 1 site in United States.
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 3 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 7 Dec 2017. 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 United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Dec 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
The Number of Polyoma BK Viremia Patients (time frame: 12 months). The study lists 3 primary outcomes in all. 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 7 Dec 2017.