Renal TransplantPhase 4NCT01935128
Evaluation of Calcineurin-inhibitor Reduction With Conversion at 2 Months to Everolimus/Reduced Tacrolimus in Renal Transplant Recipients Following Campath® Induction
A Phase 4 study testing Arm 1 Everolimus/Reduced dose tacrolimus in people with Renal Transplant, run by University of Toledo Health Science Campus at 1 site in United States.
Trial summary
The purpose of this study is to evaluate whether conversion to everolimus (Zortress®), allowing the elimination or reduction of calcineurin inhibitors, will reduce nephrotoxicity (measured by increased creatinine clearance) and lengthen overall graft (kidney transplant) survival (measured by 2-3 year graft survival). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Transplant
- What is being tested?
- Arm 1 Everolimus/Reduced dose tacrolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Jul 2013to Jul 2020
- Phase
- Phase 4
- 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
- Male or female renal allograft recipients at least 18 years old.
- Patients who have given written informed consent to participate in the study. If consent cannot be expressed in writing, it must be formally documented and witnessed, ideally via an independent trusted witness.
- Patient who has received a kidney transplant from a deceased or living unrelated-/related donor.
- Recipient of a kidney allograft with a cold ischemia time (CIT) < 36 hours.
- Female patients must have a negative pregnancy test prior to study enrollment.
- Patients on calcineurin inhibitor(s) (CNI) (tacrolimus and myfortic®) without steroid maintenance following Campath® induction.
- Patients with an acceptable allograft function defined by a serum creatinine < 2.5 mg/dL (250 μmol/L) and an actual estimated glomerular filtration rate (eGFR) (Modification of diet in renal disease equation 4, MDRD4) ≥ 30 mL/min/1.73m2 (without renal replacement therapy).
- No evidence of rejection since the time of transplantation.
Who cannot join
- Recipient of ABO incompatible allograft or a positive cross-match.
- Patient who is human immunodeficiency virus (HIV) positive.
- Patient who received an allograft from a Hepatitis B surface Antigen (HBsAg) or a Hepatitis C Virus (HCV) positive donor.
- HBsAg and/or a HCV positive patient with evidence of elevated liver function tests (LFTs) (Alanine transaminase/Aspartate transaminase [ALT/AST] levels ≥ 2.5 times upper limit of normal [ULN]). Viral serology results obtained within 6 months prior to randomization are acceptable.
- Patient with severe restrictive (total lung capacity [TLC] < 50%) or obstructive pulmonary (forced expiratory volume in one second [FEV1] < 50) disorders.
- Patient with severe allergy requiring acute (within 4 weeks of baseline) or chronic treatment that would prevent patient from potential exposure to everolimus, or with hypersensitivity to drugs similar to everolimus (e.g. macrolides).
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- Patients with a known hypersensitivity/contraindication to any of the immunosuppressants or their classes, or to any of the excipients.
- Patient with severe hypercholesterolemia (> 300 mg/dL) or hypertriglyceridemia (> 400 mg/dL) that cannot be controlled despite lipid lowering therapy.
- Patient with white blood cell (WBC) count ≤ 1,000 /mm3 (and absolute neutrophil count [ANC] of <500) or a platelet count ≤ 50,000 /mm3.
- History of malignancy of any organ system, treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases. (Localized basal cell carcinoma of the skin at any time, or small (less than 4 cm) or low-grade renal cancers, bladder cancers, or treated prostate cancer with no evidence of disease after 2 years are allowable)
- Graft loss.
- Patient on renal replacement therapy.
- Patient who experienced biopsy proven rejection.
- Proteinuria > 1 g/day (as calculated from the urinary protein-to-creatinine ratio).
- Patients with recurrence of Focal Segmental Glomerulosclerosis (FSGS).
- Patient who has a current severe systemic infection according to the investigator judgment requiring continued therapy that would interfere with the objectives of the study.
- Patients with ongoing wound healing problems, clinically significant infection requiring continued therapy or other severe surgical complication in the opinion of the investigator.
- Presence of intractable immunosuppressant complications or side effects.
- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive serum human chorionic gonadotrophin laboratory test (>5 mIU/mL)
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they are using two birth control methods.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Toledo, Health Science Campus
Toledo, Ohio, 43614
About this study
Official title: A 24-month, Single Center, Pilot, Open Label, Controlled Trial to Evaluate the Efficacy and Safety of Calcineurin-inhibitor Reduction With Conversion at 2 Months to Reduced Dose Tacrolimus/Everolimus in Adult Renal Transplant Recipients Following Campath® Induction and Steroid Avoidance
The purpose of this study is to evaluate whether conversion to everolimus (Zortress®), allowing the elimination or reduction of calcineurin inhibitors, will reduce nephrotoxicity (measured by increased creatinine clearance) and lengthen overall graft (kidney transplant) survival (measured by 2-3 year graft survival).
Read the detailed description
The purpose of this study is to evaluate whether conversion to everolimus (Zortress®), allowing the elimination or reduction of calcineurin inhibitors, will reduce nephrotoxicity (measured by increased creatinine clearance) and lengthen overall graft (kidney transplant) survival (measured by 2-3 year graft survival). Among the worst of the long-term effects of chronic immunosuppression are the nephrotoxicity (toxic to kidney cells) of the calcineurin inhibitors and the myriad complications of steroids. This protocol evaluates the elimination or reduction of calcineurin inhibitors in a protocol that has already successfully eliminated the long-term use of steroids. A considerable need remains for safer therapeutic agents that inhibit T-cell activation (a white blood cell that attacks foreign cells as part of the immune response) via a calcineurin independent or reduced-dose mechanism of action.
- Conditions
- Renal Transplant
- Being tested
- Arm 1 Everolimus/Reduced dose tacrolimus
- Keywords
- Renal Transplant, Immunosuppression, Steroid Avoidance, Calcineurin Avoidance, Mammalian Target of Rapamycin (mTOR), Kidney
- Medical subject headings
- Hereditary Sensory and Autonomic Neuropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Arm 1 Everolimus/Reduced dose tacrolimusDrug
Also called Zortress®, Prograf® or Hecoria®
Immunosuppression drug intervention
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 Everolimus/Reduced dose tacrolimus | Experimental | In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml. Receives: Drug: Arm 1 Everolimus/Reduced dose tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Renal Function
Renal function in patients will be assessed using glomerular filtration rate (GFR) as measured by the Modified Diet Renal Disease (MDRD) estimation.
Glomerular filtration is the process by which the kidneys filter the blood, removing excess wastes and fluids. Glomerular filtration rate (GFR) is a calculation that determines how well the blood is filtered by the kidneys, which is one way to measure remaining kidney function. GFR is also used to find the stage of chronic kidney disease. Glomerular filtration rate is usually calculated using a mathematical formula that compares a person's size, age, sex, and race to serum creatinine levels. The higher the GFR number, the better the kidney function; the lower the GFR number, the worse the kidney function. A GFR of 60 or higher is in the normal range. A GFR below 60 may mean kidney disease. A GFR of 15 or lower may mean kidney failure.
Measured: 2 years
Graft Survival
Graft survival is defined as the percentage of kidney transplants still functioning at 2 years post baseline visit . One patient died of natural causes at 12 months with a functioning graft.
Measured: 2 years
Biopsy Proven Acute Rejection
The percentage of patients with a treated biopsy-proven acute rejection (a co-primary endpoint) within the 2 year study time period
Measured: 2 years
Patient Survival
Patient survival is defined as the percentage of patients still surviving at 2 years post baseline visit
Measured: 2 years
Secondary outcomes (16)
Impaired Glucose Tolerance
The number of patients with impaired glucose tolerance as indicated by fasting blood glucose levels, Hemoglobin A1C (HgbA1C) levels and the need for hypoglycemic medications
Measured: 2 years
Proteinuria
The number of patients with proteinuria as defined by spot urine protein to creatinine ratio greater than 1.0
Measured: 2 years
Lipid Levels
The number of patients with hyperlipidemia as defined by the development of new onset hyperlipidemia in the baseline negative patients and the number of baseline positive patients who required starting a new lipid-lowering medication or an increase in dose of their lipid-lowering medication over the course of the study
Measured: 2 years
Mouth Ulcers
The number of patients with stomatitis/aphthous ulcer
Measured: 2 years
Gastrointestinal Complaints
The number of patients with gastrointestinal complaints as indicated by abdominal pain, nausea, vomiting or diarrhea not accounted for by a specific episode of illness such as gastroenteritis
Measured: 2 years
Leukopenia
The number of patients with leukopenia as indicated by white blood cell count less than 1.0, absolute neutrophil count less than 500 or the need for exogenous granulocyte stimulating factor administration
Measured: 2 years
Thrombocytopenia
The number of patients with thrombocytopenia as defined by platelet count less than 50
Measured: 2 years
Neurotoxicity
The number of patients with neurotoxicity as evidenced by incidence of new onset seizure activity or tremors
Measured: 2 years
Pneumonitis
The number of patients with pneumonitis as demonstrated by lung inflammation symptoms such as shortness of breath and/or cough requiring clinical intervention and management
Measured: 2 years
Cytomegalovirus
The number of patients with Incidence of cytomegalovirus infection as defined by need for hospitalization
Measured: 2 years
Infection Requiring Hospitalization
The number of patients with serious infections as defined by need for hospitalization
Measured: 2 years
BK Infection
The number of patients with BK infection as defined by blood titers requiring reduction in immunosuppressive dose
Measured: 2 years
BK Nephropathy
The number of patients with BK nephropathy as defined by biopsy. Note that biopsies were not required as part of the study but were only done as part of the patient's standard of care if rejection was suspected (i.e. if the serum creatinine increased by 25% and was not associated with elevated tacrolimus levels or clinical signs of dehydration/illness to account for elevated creatinine)
Measured: 2 years
Malignancies
The number of patients developing malignancies including post-transplant lymphoproliferative disorders
Measured: 2 years
Cardiovascular Complications
The number of patients with cardiovascular complications as indicated by conditions such as dysrhythmias, coronary artery disease requiring intervention or myocardial infarction
Measured: 2 years
Development of Donor Specific Antibody
The number of patients with incidence of development of donor specific antibody
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2013 (estimated)
- Study start3 Jul 2013
- Primary completionJul 2020
- Study completionJul 2020
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 Renal TransplantStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Toledo Health Science Campus
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Responsible party
- Principal investigator, Michael A. Rees, MD, PhD, University of Toledo Health Science Campus
- Investigators
- Michael Rees, MD, PhD, Principal investigator, University of Toledo, HSC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01935128
- Sponsor's protocol ID
- Everolimus
- Status last verified
- May 2022
- First submitted
- 21 Aug 2013
- Last updated
- 26 May 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 24-month, Single Center, Pilot, Open Label, Controlled Trial to Evaluate the Efficacy and Safety of Calcineurin-inhibitor Reduction With Conversion at 2 Months to Reduced Dose Tacrolimus/Everolimus in Adult Renal Transplant Recipients Following Campath® Induction and Steroid Avoidance
- ClinicalTrials.gov ID
- NCT01935128
- Acronym / sponsor ID
- Everolimus
- Conditions
- Renal Transplant
- Keywords
- Renal Transplant, Immunosuppression, Steroid Avoidance, Calcineurin Avoidance, Mammalian Target of Rapamycin (mTOR), Kidney
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- University of Toledo Health Science CampusUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- 3 Jul 2013 (actual)
- Primary completion
- Jul 2020 (actual)
- Study completion
- Jul 2020 (actual)
- First posted
- 4 Sep 2013 (estimated)
- Results
- Posted 26 May 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate whether conversion to everolimus (Zortress®), allowing the elimination or reduction of calcineurin inhibitors, will reduce nephrotoxicity (measured by increased creatinine clearance) and lengthen overall graft (kidney transplant) survival (measured by 2-3 year graft survival).
Detailed description
The purpose of this study is to evaluate whether conversion to everolimus (Zortress®), allowing the elimination or reduction of calcineurin inhibitors, will reduce nephrotoxicity (measured by increased creatinine clearance) and lengthen overall graft (kidney transplant) survival (measured by 2-3 year graft survival). Among the worst of the long-term effects of chronic immunosuppression are the nephrotoxicity (toxic to kidney cells) of the calcineurin inhibitors and the myriad complications of steroids. This protocol evaluates the elimination or reduction of calcineurin inhibitors in a protocol that has already successfully eliminated the long-term use of steroids. A considerable need remains for safer therapeutic agents that inhibit T-cell activation (a white blood cell that attacks foreign cells as part of the immune response) via a calcineurin independent or reduced-dose mechanism of action.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm 1 Everolimus/Reduced dose tacrolimus | Experimental | Drug: Arm 1 Everolimus/Reduced dose tacrolimusIn this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male or female renal allograft recipients at least 18 years old.
- Patients who have given written informed consent to participate in the study. If consent cannot be expressed in writing, it must be formally documented and witnessed, ideally via an independent trusted witness.
- Patient who has received a kidney transplant from a deceased or living unrelated-/related donor.
- Recipient of a kidney allograft with a cold ischemia time (CIT) < 36 hours.
- Female patients must have a negative pregnancy test prior to study enrollment.
Key exclusion criteria (20 listed)
- Recipient of ABO incompatible allograft or a positive cross-match.
- Patient who is human immunodeficiency virus (HIV) positive.
- Patient who received an allograft from a Hepatitis B surface Antigen (HBsAg) or a Hepatitis C Virus (HCV) positive donor.
- HBsAg and/or a HCV positive patient with evidence of elevated liver function tests (LFTs) (Alanine transaminase/Aspartate transaminase [ALT/AST] levels ≥ 2.5 times upper limit of normal [ULN]). Viral serology results obtained within 6 months prior to randomization are acceptable.
- Patient with severe restrictive (total lung capacity [TLC] < 50%) or obstructive pulmonary (forced expiratory volume in one second [FEV1] < 50) disorders.
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 |
|---|---|---|
| Arm 1 Everolimus/Reduced dose tacrolimusAlso: Zortress®, Prograf® or Hecoria®Immunosuppression drug intervention | Drug | Arm 1 Everolimus/Reduced dose tacrolimus |
Primary outcome
Renal Function
Time frame: 2 years
Renal function in patients will be assessed using glomerular filtration rate (GFR) as measured by the Modified Diet Renal Disease (MDRD) estimation. Glomerular filtration is the process by which the kidneys filter the blood, removing excess wastes and fluids. Glomerular filtration rate (GFR) is a calculation that determines how well the blood is filtered by the kidneys, which is one way to measure remaining kidney function. GFR is also used to find the stage of chronic kidney disease. Glomerular filtration rate is usually calculated using a mathematical formula that compares a person's size, age, sex, and race to serum creatinine levels. The higher the GFR number, the better the kidney function; the lower the GFR number, the worse the kidney function. A GFR of 60 or higher is in the normal range. A GFR below 60 may mean kidney disease. A GFR of 15 or lower may mean kidney failure.
Graft Survival
Time frame: 2 years
Graft survival is defined as the percentage of kidney transplants still functioning at 2 years post baseline visit . One patient died of natural causes at 12 months with a functioning graft.
Biopsy Proven Acute Rejection
Time frame: 2 years
The percentage of patients with a treated biopsy-proven acute rejection (a co-primary endpoint) within the 2 year study time period
Patient Survival
Time frame: 2 years
Patient survival is defined as the percentage of patients still surviving at 2 years post baseline visit
16 secondary outcomes
Impaired Glucose Tolerance
Time frame: 2 years
Proteinuria
Time frame: 2 years
Lipid Levels
Time frame: 2 years
Mouth Ulcers
Time frame: 2 years
Gastrointestinal Complaints
Time frame: 2 years
Leukopenia
Time frame: 2 years
Thrombocytopenia
Time frame: 2 years
Neurotoxicity
Time frame: 2 years
Pneumonitis
Time frame: 2 years
Cytomegalovirus
Time frame: 2 years
Infection Requiring Hospitalization
Time frame: 2 years
BK Infection
Time frame: 2 years
BK Nephropathy
Time frame: 2 years
Malignancies
Time frame: 2 years
Cardiovascular Complications
Time frame: 2 years
Development of Donor Specific Antibody
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 May 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Michael Rees, MD, PhD principal investigator
University of Toledo, HSC
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 Arm 1 Everolimus/Reduced dose tacrolimus in people with Renal Transplant, run by University of Toledo Health Science Campus 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 8 inclusion and 20 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 26 May 2022. 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 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?
Yes. Results are posted in the registry (first posted 26 May 2022). 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?
Renal Function (time frame: 2 years). The study lists 4 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 26 May 2022.