A Phase 2/3 interventional study of Everolimus and Tacrolimus in Delayed Graft Function, sponsored by Matthew Cooper. Terminated at 1 site in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2019-04-26.
Sponsored by Matthew Cooper · Phase 2/3, Interventional, and Treatment
The purpose of this pilot study is to evaluate concentration-controlled everolimus with low dose tacrolimus compared to early conversion to CNI-free regimen and MMF/MPA with standard dose tacrolimus in de novo renal transplant recipients of ECD/DCD kidneys. Given tacrolimus and MMF/MPA is a widely prescribed immunosuppressive regimen in the United States, comparisons of tacrolimus and MMF/MPA regimens to investigational therapies and treatment regimens are needed. Also, considering the fact that ECD/DCD is a fast growing fraction of donors, evaluation of various regimens' effects on rather delicate ECD/DCD kidneys is necessary.
The purpose of this pilot study is to evaluate concentration-controlled everolimus with low dose tacrolimus compared to early conversion to CNI-free regimen and MMF/MPA with standard dose tacrolimus in de novo renal transplant recipients of ECD/DCD kidneys. Given tacrolimus and MMF/MPA is a widely prescribed immunosuppressive regimen in the United States, comparisons of tacrolimus and MMF/MPA regimens to investigational therapies and treatment regimens are needed. Also, considering the fact that ECD/DCD is a fast growing fraction of donors, evaluation of various regimens' effects on rather delicate ECD/DCD kidneys is necessary.
The primary objective of this study is to evaluate concentration-controlled everolimus and low dose tacrolimus compared to MMF/MPA with standard dose tacrolimus at 24 months post-transplant with respect to the composite efficacy failure rates (treated biopsy proven acute rejection episodes (BPAR), graft loss, death, loss to follow-up) in de novo renal transplant recipients.
The key secondary objective is to compare renal function of the everolimus treatment arms to the MMF/MPA treatment arm at 12 and 24 months post-transplantation. Renal function will be measured by the calculated glomerular filtration rate (GFR), using the MDRD (Modification of Diet in Renal Disease) formula (20).
83 studies on the registry are indexed under Delayed Graft Function; 15 are open to participants now.
This study's enrollment of 25 is below the median of 90 across 62 interventional studies indexed under Delayed Graft Function.
Browse Delayed Graft Function studies →This is the only study on the registry with Matthew Cooper as lead sponsor.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Male or female recipients 18-65 years of age undergoing primary or secondary kidney transplantation
Recipients of primary or secondary cadaveric, ECD/DCD kidney (defined as follows)
Donor whose heart has irreversibly stopped beating, previously referred to as non-heart-beating or asystolic donation
Brain-dead donor > 60 years old
Donor aged 50-59 years old with two of the following criteria:
History of hypertension
Terminal serum creatinine ≥ 1.5 mg/dL
Death resulting from cerebrovascular accident
Patients who have given written to participate in the study
Exclusion Criteria:
Cold ischemic time (CIT) > 30 hours
Patients who are ABO incompatible transplants, or T, or B cell crossmatch positive transplant
Patients with a known to any of the study drugs or to drugs of similar chemical class
Non-controlled DCD
Donor age >70
Patients with >32 at baseline before surgery
Pregnant or lactating females
Females of unwilling to use an effective means of or are planning to become pregnant
Patients with count \<100,000/mm3 at the evaluation before randomization.
Patients with an of \< 1,500/mm³ at baseline before surgery or white blood cell count of \< 4,500/mm³
Patients who are recipients of multiple solid organ transplants
Patients who have severe hypercholesterolemia (>350 mg/dL; >9 mmol/L) or hypertriglyceridemia (>500 mg/dL; >5.6 mmol/L). Patients with controlled hyperlipidemia are acceptable
Patients who have an abnormal liver profile such as , AST, Alk Phos or total >3 times the upper normal limit
Patients who are treated with drugs that are strong inducers or inhibitors of cytochrome P450 3A4, such as terfenadine, astemizole, cisapride, erythromycin, azithromycin, itraconazole, rifampin or lovastatin
Patients who received an drug or who have been treated with a non-protocol drug or treatment within 30 days or 5 half-lives prior to randomization
Patients with a history of of any organ system, treated or untreated, within the past 2 years whether or not there is evidence of local recurrence or , with the exception of localized basal cell carcinoma of the skin
Patients who are -positive or (PCR+ only) or B surface antigen positive
Recipients of organs from donors who test positive for surface antigen or Hepatitis C (PCR+ only) are excluded
Patients with a history of severe diarrhea, active peptic ulcer disease, or uncontrolled diabetes mellitus ( A1c \<7.0 %) at baseline
Patients who have any surgical or medical condition, which in the opinion of the investigator, might significantly alter the absorption, distribution, metabolism and excretion of study medication, and/or the presence of severe diarrhea or active peptic ulcer
Patients who have cardiac failure (e.g. resting dyspnea, symptoms with less than ordinary activity, marked limitation of activity) at time of screening or any other severe cardiac disease as determined by the investigator
Patients with abnormal physical or laboratory findings of clinical significance within 3 months of randomization which would interfere with the objectives of the study
Patients with any history of coagulopathy or medical condition requiring long-term anticoagulation therapy after transplantation (Low dose aspirin treatment is allowed)
Patients with known history of focal segmental glomeruloscrelosis
Presence of psychiatric illness (i.e., schizophrenia, bipolar, major depression) that, in the opinion of the investigator, would interfere with study requirements
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Concentration controlled everolimus(ERL) \& Low dose tacrolimus(TAC) + corticosteroid withdraw
Drug: Everolimus · Drug: Tacrolimus
Concentration controlled everolimus \& low dose tacrolimus --\> mycophenolate mofetil (MMF) at Month 3 + corticosteroid
Drug: Everolimus · Drug: Tacrolimus · Drug: Mycophenolate mofetil (MMF/MPA)
Standard dose of tacrolimus + mycophenolate mofetil + corticosteroid withdraw
Drug: Tacrolimus · Drug: Mycophenolate mofetil (MMF/MPA)
One of the immunosuppressants currently being evaluated to replace CNIs in patients with CNI nephropathy is the mammalian Target of Rapamycin (mTOR) inhibitor, Sirolimus. Everolimus is a derivative of Sirolimus and belongs to this class of immunosuppressants, therefore, both drugs have similar side effect profile. The half-life of Everolimus is almost half of Sirolimus (Everolimus 30 hours vs Sirolimus 62 hours), which makes its dose adjustment easier although it would require more frequent dosing. In clinical trials, Everolimus has demonstrated its potential role as a safe alternative in minimizing and/or eliminating CNI such as Cyclosporin A and Tacrolimus .
Also known as: Zortress
One of the immunosuppressants currently being evaluated to replace CNIs in patients with CNI nephropathy is the mammalian Target of Rapamycin (mTOR) inhibitor, Sirolimus. Everolimus is a derivative of Sirolimus and belongs to this class of immunosuppressants, therefore, both drugs have similar side effect profile. The half-life of Everolimus is almost half of Sirolimus (Everolimus 30 hours vs Sirolimus 62 hours), which makes its dose adjustment easier although it would require more frequent dosing. In clinical trials, Everolimus has demonstrated its potential role as a safe alternative in minimizing and/or eliminating CNI such as Cyclosporin A and Tacrolimus.
Also known as: Prograf
Drug page: Mycophenolic Acid
Control Drug
Also known as: CellCept
Evaluate Concentration-controlled Everolimus and Low Dose Tacrolimus Compared to MMF/MPA With Standard Dose Tacrolimus at 24 Months
The primary objective of this study is to evaluate concentration-controlled everolimus and low dose tacrolimus compared to MMF/MPA with standard dose tacrolimus at 24 months post-transplant with respect to the composite efficacy failure rates (treated biopsy proven acute rejection episodes (BPAR), graft loss, death, loss to follow-up) in de novo renal transplant recipients.
Time frame: 24 months
Compare Renal Function of the Everolimus Treatment Arms to the MMF/MPA Treatment Arm at 12 and 24 Months Post-transplantation
The key secondary objective is to compare renal function of the everolimus treatment arms to the MMF/MPA treatment arm at 12 and 24 months post-transplantation. Renal function will be measured by the calculated glomerular filtration rate (GFR), using the MDRD (Modification of Diet in Renal Disease) formula (20).
Time frame: 24 months
Incidence of Cytomegalovirus (CMV) (Viremia or Viruria)
Time frame: 24 months
| Milestone | ERL & TAC | ERL & TAC --> MMF/MPA | Standard Dose TAC + MMF/MPA |
|---|---|---|---|
| Started | 9 | 9 | 7 |
| Completed | 0 | 0 | 0 |
| Not completed | 9 | 9 | 7 |
The primary objective of this study is to evaluate concentration-controlled everolimus and low dose tacrolimus compared to MMF/MPA with standard dose tacrolimus at 24 months post-transplant with respect to the composite efficacy failure rates (treated biopsy proven acute rejection episodes (BPAR), graft loss, death, loss to follow-up) in de novo renal transplant recipients.
No measurements were reported for this outcome.
The key secondary objective is to compare renal function of the everolimus treatment arms to the MMF/MPA treatment arm at 12 and 24 months post-transplantation. Renal function will be measured by the calculated glomerular filtration rate (GFR), using the MDRD (Modification of Diet in Renal Disease) formula (20).
No measurements were reported for this outcome.
No measurements were reported for this outcome.
Collected over Adverse events were recorded from the time of study drug through the end of the study. The study was terminated prematurely.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| ERL & TAC | 0/9 (0%) | 7/9 (77.8%) | 8/9 (88.9%) |
| ERL & TAC --> MMF/MPA | 0/9 (0%) | 2/9 (22.2%) | 9/9 (100%) |
| Standard Dose TAC + MMF/MPA | 0/7 (0%) | 2/7 (28.6%) | 7/7 (100%) |
| Event | ERL & TAC | ERL & TAC --> MMF/MPA | Standard Dose TAC + MMF/MPA |
|---|---|---|---|
| Sepsis and Multiple Organ FailureInfections and infestations | 0/9 | 0/9 | 1/7 |
| ER Admission for Blood TransfusionBlood and lymphatic system disorders | 0/9 | 0/9 | 1/7 |
| ConstipationGastrointestinal disorders | 1/9 | 0/9 | 0/7 |
| GI SurgerySurgical and medical procedures | 1/9 | 0/9 | 0/7 |
| Left Renal Mass/NephrectomyRenal and urinary disorders | 0/9 | 1/9 | 0/7 |
| Neck and Facial EdemaGeneral disorders | 1/9 | 0/9 | 0/7 |
| AdmissionSurgical and medical procedures | 1/9 | 0/9 | 0/7 |
| UTIRenal and urinary disorders | 1/9 | 0/9 | 0/7 |
| Hydronephrosis (Possible malrotation of kidney, possible uretropelvic junction obstruction)Renal and urinary disorders | 1/9 | 0/9 | 0/7 |
| Fluid Overload and Chest PressureRespiratory, thoracic and mediastinal disorders | 0/9 | 1/9 | 0/7 |
| Event | ERL & TAC | ERL & TAC --> MMF/MPA | Standard Dose TAC + MMF/MPA |
|---|---|---|---|
| Electrolyte ImbalanceMetabolism and nutrition disorders | 4/9 | 4/9 | 5/7 |
| HyperkalemiaMetabolism and nutrition disorders | 5/9 | 6/9 | 0/7 |
| Delayed Graft FunctionRenal and urinary disorders | 1/9 | 4/9 | 2/7 |
| BK ViremiaInfections and infestations | 3/9 | 2/9 | 2/7 |
| ProteinuriaRenal and urinary disorders | 1/9 | 3/9 | 1/7 |
| CMVInfections and infestations | 1/9 | 0/9 | 2/7 |
| Elevated Serum CreatinineInvestigations | 1/9 | 2/9 | 2/7 |
| Shortness of BreathRespiratory, thoracic and mediastinal disorders | 0/9 | 0/9 | 2/7 |
| AnemiaBlood and lymphatic system disorders | 2/9 | 2/9 | 2/7 |
| LeukopeniaBlood and lymphatic system disorders | 1/9 | 0/9 | 2/7 |
| Age, Categorical(Participants) | ERL & TAC | ERL & TAC --> MMF/MPA | Standard Dose TAC + MMF/MPA | Total |
|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 9 | 9 | 6 | 24 |
| >=65 years | 0 | 0 | 1 | 1 |
| Sex: Female, Male(Participants) | ERL & TAC | ERL & TAC --> MMF/MPA | Standard Dose TAC + MMF/MPA | Total |
|---|---|---|---|---|
| Female | 3 | 3 | 2 | 8 |
| Male | 6 | 6 | 5 | 17 |
| Ethnicity (NIH/OMB)(Participants) | ERL & TAC | ERL & TAC --> MMF/MPA | Standard Dose TAC + MMF/MPA | Total |
|---|---|---|---|---|
| Hispanic or Latino | 1 | 1 | 0 | 2 |
| Not Hispanic or Latino | 8 | 8 | 7 | 23 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | ERL & TAC | ERL & TAC --> MMF/MPA | Standard Dose TAC + MMF/MPA | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 8 | 6 | 7 | 21 |
| White | 0 | 2 | 0 | 2 |
| More than one race | 1 | 0 | 0 | 1 |
| Unknown or Not Reported | 0 | 1 | 0 | 1 |
| Region of Enrollment(participants) | ERL & TAC | ERL & TAC --> MMF/MPA | Standard Dose TAC + MMF/MPA | Total |
|---|---|---|---|---|
| United States | 9 | 9 | 7 | 25 |
PDFs hosted by the registry, ClinicalTrials.gov.
This study is terminated, as verified in Apr 2019. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Everolimus