ImmunosuppressionNCT01936519

Conversion to Everolimus From Calcineurin Inhibitor With Mycophenolic Acid: Impact on Long Term Renal Function in Liver Transplantation.

A study testing Arm A: Everolimus and Calcineurin Inhibitor in people with Immunosuppression and Renal Failure, run by Milton S. Hershey Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This study will examine the renal sparing impact of implementing a strategy of conversion to everolimus from a calcineurin inhibitor based immunosuppressive protocol at 3 months post liver transplant Read more about this study

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Immunosuppression, Renal Failure
What is being tested?: Arm A: Everolimus and Calcineurin Inhibitor
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 24 participants
Where: 1 siteUnited States
Study dates: 16 Dec 2013to 31 Jul 2019
Phase: Interventional
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 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Ability and willingness to provide written informed consent and adhere to study regimen.
Primary deceased donor liver transplant recipients 18-70 years of age
Functioning allograft at randomization (AST, ALT, Total Bilirubin levels ≤3 times ULN, and AlkP and GGT levels ≤ 5 times ULN). Elevated GGT alone, in combination with AST, ALT, total bilirubin and AlkP within defined range does not exclude patients from randomization.
Recipients on an immunosuppressive regimen of corticosteroids and tacrolimus.
Confirmed recipient HCV status at Screening (either by serology or PCR).
Abbreviated MDRD eGFR ≥ 30 mL/min/1.73m2. Local and central serum creatinine results within 5 days prior to randomization, however no sooner than Day 25 post-transplantation.
Verification of at least one tacrolimus trough level of ≥ 8 ng/mL one week prior to randomization. Target trough levels above 8 ng/mL prior to randomization.
Patients able to take oral medication at time of randomization.

Who cannot join

Recipients of multiple solid organ or islet cell tissue transplants, or have previously received an organ or tissue transplant. Combined liver kidney transplant recipients.
Living donor or split liver recipients.
History of malignancy of any organ system within past 5 years whether or not there is evidence of local recurrence or metastases, other than non-metastatic basal or squamous cell carcinoma of the skin or HCC.
Hepatocellular carcinoma that does not fulfill Milan criteria (1 nodule ≤ 5 cm, 2-3 nodules all < 3 cm, per explant histology of recipient liver.
Use of antibody induction therapy.
Patients with known hypersensitivity to the drugs used on study or their class, or to any of the excipients.

Show all 20Show fewer

Recipients of ABO incompatible transplant grafts.
Recipients of Hepatitis B surface antigen or HIV donor organs.
Surgical or medical condition, which might significantly alter absorption, distribution, metabolism and excretion of study drug.
Women of child-bearing potential (WOCBP): 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 (1) they meet the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels >40 mIU/m, or (2) have past 6 weeks from surgical bilateral oophorectomy with or without hysterectomy or (3) are using one or more of the following methods of contraception: surgical sterilization (e.g., bilateral tubal ligation, vasectomy), hormonal contraception (implantable, patch, oral), copper coated IUD and double-barrier methods ( any double combination of male or female condom with spermicidal gel, diaphragm, sponge, cervical cap). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Reliable contraception should be maintained throughout and for 3 months after study drug discontinuation.
History of coagulopathy or medical condition requiring long-term anticoagulation which would preclude liver biopsy after transplantation. (Low dose aspirin treatment or interruption of chronic anticoagulant is allowed).
Enrollment Exclusion - Randomization
Severe hypercholesterolemia (>350 mg/dL; >9 mmol/L) or hypertriglyceridemia (>500 mg/dL; >8.5 mmol/L) within 6 months of transplantation. Controlled hyperlipidemia is acceptable at time of randomization.
Platelet count < 50,000/mm3 at randomization.
Absolute neutrophil count < 1,000/mm³ or white blood cell count <2,000/mm³ at randomization.
Patients positive for HIV: Negative laboratory results within 6 months before randomization are acceptable.
Clinically significant systemic infection requiring IV antibiotics at randomization. Patients in a critical care setting at randomization requiring life support measures such as mechanical ventilation, dialysis, or vasopressor agents.
Patients on renal replacement therapy within 7 days prior to randomization.
Thrombosis of major hepatic arteries, major hepatic veins, portal vein and inferior vena cava. Results obtained within 5 days prior to randomization are acceptable, however no sooner than Day 25 post-transplantation.
Acute rejection requiring antibody therapy or more than one steroid sensitive episode of acute rejection during the run-in period. Includes patients who have not completed steroid treatment for acute rejection within 7 days prior to randomization.

Trial locations and contacts

1 site in 1 country.

United States1 site

Penn State College of Medicine; Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, 17033

Other trials in United States

About this study

Official title: A Randomized Prospective Trial of Conversion to Everolimus Therapy From Calcineurin Inhibitor Based Maintenance Immunosuppression in Association With Mycophenolic Acid in Liver Transplantation: Examination of Impact on Long Term Renal Function.

This study will examine the renal sparing impact of implementing a strategy of conversion to everolimus from a calcineurin inhibitor based immunosuppressive protocol at 3 months post liver transplant

Read the detailed description

Given the increasing proportion of patients having renal failure at the time of transplant, with the nephrotoxic effect of calcineurin inhibitor based immunosuppression associated with its long term negative survival impact, this study proposes to examine the renal sparing impact of conversion to everolimus from a calcineurin inhibitor based immunosuppressive protocol at 3 months post liver transplant. The 3 month time point was chosen to allow for the switch to everolimus to occur at a period of stable post transplant liver function when both technical and rejection risks are lower. The 3 month cut off was also chosen because of data indicating that worsening renal function at 4 weeks, 3 months and 1 year post transplant is an independent risk factor for the development of chronic renal failure and end stage renal disease after orthotopic liver transplantation. 24 patients will be randomized into 2 arms:

Arm A: Conversion to Everolimus immunosuppression combined with mycophenolic acid (Myfortic: MPA), and complete discontinuation of Calcineurin inhibitor at 3 months post transplant.

Arm B: Continuation with standard immunosuppressive therapy consisting of Calcineurin inhibitor associated with mycophenolic acid (Myfortic: MPA).

Follow up: 2 years.

Conditions: Immunosuppression, Renal Failure
Being tested: Arm A: Everolimus, Calcineurin Inhibitor
Keywords: Everolimus, Zortress, Renal Function, Tacrolimus, Cyclosporine, Myfortic, Mycophenolic Acid, Liver Transplantation
Medical subject headings: Renal Insufficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Arm A: EverolimusDrug
Also called Zortress; Mycophenolic Acid (Myfortic)
Conversion to Everolimus immunosuppression combined with mycophenolic acid (Myfortic: MPA), and complete discontinuation of Calcineurin inhibitor at 3 months post transplant.
Calcineurin InhibitorDrug
Also called Tacrolimus (Prograf), Cyclosporine (Gengraf), Mycophenolic Acid (Myfortic)
Comparison Arm: Continuation with standard immunosuppressive therapy consisting of Calcineurin inhibitor associated with mycophenolic acid (Myfortic: MPA).

Study groups in NCT01936519
Study group	Role	What they receive
Calcineurin Inhibitor with Mycophenolic Acid	Active comparator	Calcineurin inhibitor immunosuppression with mycophenolic acid Receives: Drug: Calcineurin Inhibitor
Everolimus with Mycophenolic Acid	Experimental	Conversion to Everolimus immunosuppression combined with mycophenolic acid (Myfortic: MPA), and complete discontinuation of Calcineurin inhibitor at 3 months post transplant. Receives: Drug: Arm A: Everolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

Renal Function as Measured by 24 Hour Urine Creatinine Clearance
Renal Function was assessed by 24 hr urine collection creatinine clearance measured (mL/min). 24 Hr urine collection was assessed at baseline, 6 months, 1 year, and 2 years post transplant.
Measured: 6 months, 1 year, and 2 years
Renal Function as Measured by Serum Creatinine Level
Serum creatinine levels were assessed at 6 months, 1 year, and 2 years post transplant
Measured: 6 months, 1 year, and 2 years
Renal Function as Measured by Cockcroft Gault Creatinine Clearance
The Cockcroft-Gault formula for estimating creatinine clearance was determined at 6 months, 1 year, and 2 years post transplant
Measured: 6 months, 1 year, and 2 years
Renal Function as Measured by Modification of Diet in Renal Disease (MDRD) Estimated Glomerular Filtration Rate (eGFR)
Modification of Diet in Renal Disease (MDRD) estimated Glomerular Filtration Rate (eGFR) was assessed at 6 months, 1 year, and 2 years post transplant.
Measured: 6 months, 1 year, and 2 years
Renal Function as Measured by Iothalamate Clearance
Iothalamate Clearance was assessed at 6 months, 1 year, and 2 years post transplant.
Measured: 6 months, 1 year, and 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

16 Dec 201331 Jul 2019

First posted6 Sep 2013 (estimated)
Study start16 Dec 2013
Primary completion31 Jul 2019
Study completion31 Jul 2019

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.
Publications (29)Papers the sponsor has linked to this study.
Other trials for ImmunosuppressionStudies of the same condition, open and under way.
More trials run by Milton S. Hershey Medical CenterThe sponsor's other registered studies.
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 N/A
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 24 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01936519
Sponsor's protocol ID: IRB 38115
Status last verified: Jan 2021
First submitted: 16 Aug 2013
Last updated: 29 Jan 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Yes: Plan to publish de-identified data

Publications

Burra P, Senzolo M, Masier A, Prestele H, Jones R, Samuel D, Villamil F. Factors influencing renal function after liver transplantation. Results from the MOST, an international observational study. Dig Liver Dis. 2009 May;41(5):350-6. doi: 10.1016/j.dld.2008.09.018. Epub 2008 Nov 28.
PubMed 19046932
Gonwa TA, Mai ML, Melton LB, Hays SR, Goldstein RM, Levy MF, Klintmalm GB. End-stage renal disease (ESRD) after orthotopic liver transplantation (OLTX) using calcineurin-based immunotherapy: risk of development and treatment. Transplantation. 2001 Dec 27;72(12):1934-9. doi: 10.1097/00007890-200112270-00012.
PubMed 11773892
Ojo AO, Held PJ, Port FK, Wolfe RA, Leichtman AB, Young EW, Arndorfer J, Christensen L, Merion RM. Chronic renal failure after transplantation of a nonrenal organ. N Engl J Med. 2003 Sep 4;349(10):931-40. doi: 10.1056/NEJMoa021744.
PubMed 12954741
Velidedeoglu E, Bloom RD, Crawford MD, Desai NM, Campos L, Abt PL, Markmann JW, Mange KC, Olthoff KM, Shaked A, Markmann JF. Early kidney dysfunction post liver transplantation predicts late chronic kidney disease. Transplantation. 2004 Feb 27;77(4):553-6. doi: 10.1097/01.tp.0000114609.99558.41.
PubMed 15084934
Wadei HM, Geiger XJ, Cortese C, Mai ML, Kramer DJ, Rosser BG, Keaveny AP, Willingham DL, Ahsan N, Gonwa TA. Kidney allocation to liver transplant candidates with renal failure of undetermined etiology: role of percutaneous renal biopsy. Am J Transplant. 2008 Dec;8(12):2618-26. doi: 10.1111/j.1600-6143.2008.02426.x.
PubMed 19032225
Randhawa PS, Shapiro R. Chronic renal failure after liver transplantation. Am J Transplant. 2005 May;5(5):967-8. doi: 10.1111/j.1600-6143.2005.00819.x. No abstract available.
PubMed 15816874
McCauley J, Van Thiel DH, Starzl TE, Puschett JB. Acute and chronic renal failure in liver transplantation. Nephron. 1990;55(2):121-8. doi: 10.1159/000185938.
PubMed 2362625
Fisher NC, Nightingale PG, Gunson BK, Lipkin GW, Neuberger JM. Chronic renal failure following liver transplantation: a retrospective analysis. Transplantation. 1998 Jul 15;66(1):59-66. doi: 10.1097/00007890-199807150-00010.
PubMed 9679823
Neuberger JM, Mamelok RD, Neuhaus P, Pirenne J, Samuel D, Isoniemi H, Rostaing L, Rimola A, Marshall S, Mayer AD; ReSpECT Study Group. Delayed introduction of reduced-dose tacrolimus, and renal function in liver transplantation: the 'ReSpECT' study. Am J Transplant. 2009 Feb;9(2):327-36. doi: 10.1111/j.1600-6143.2008.02493.x. Epub 2008 Dec 15.
PubMed 19120077
Chapman TM, Perry CM. Everolimus. Drugs. 2004;64(8):861-72; discussion 873-4. doi: 10.2165/00003495-200464080-00005.
PubMed 15059040
Levy G, Schmidli H, Punch J, Tuttle-Newhall E, Mayer D, Neuhaus P, Samuel D, Nashan B, Klempnauer J, Langnas A, Calmus Y, Rogiers X, Abecassis M, Freeman R, Sloof M, Roberts J, Fischer L. Safety, tolerability, and efficacy of everolimus in de novo liver transplant recipients: 12- and 36-month results. Liver Transpl. 2006 Nov;12(11):1640-8. doi: 10.1002/lt.20707.
PubMed 16598777
Nashan B. Early clinical experience with a novel rapamycin derivative. Ther Drug Monit. 2002 Feb;24(1):53-8. doi: 10.1097/00007691-200202000-00010.
PubMed 11805723
Chan L, Greenstein S, Hardy MA, Hartmann E, Bunnapradist S, Cibrik D, Shaw LM, Munir L, Ulbricht B, Cooper M; CRADUS09 Study Group. Multicenter, randomized study of the use of everolimus with tacrolimus after renal transplantation demonstrates its effectiveness. Transplantation. 2008 Mar 27;85(6):821-6. doi: 10.1097/TP.0b013e318166927b.
PubMed 18360262
Everson GT. Everolimus and mTOR inhibitors in liver transplantation: opening the "box". Liver Transpl. 2006 Nov;12(11):1571-3. doi: 10.1002/lt.20845. No abstract available.
PubMed 17058246
De Simone P, Carrai P, Precisi A, Petruccelli S, Baldoni L, Balzano E, Ducci J, Caneschi F, Coletti L, Campani D, Filipponi F. Conversion to everolimus monotherapy in maintenance liver transplantation: feasibility, safety, and impact on renal function. Transpl Int. 2009 Mar;22(3):279-86. doi: 10.1111/j.1432-2277.2008.00768.x. Epub 2008 Dec 2.
PubMed 19054383

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 29 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized Prospective Trial of Conversion to Everolimus Therapy From Calcineurin Inhibitor Based Maintenance Immunosuppression in Association With Mycophenolic Acid in Liver Transplantation: Examination of Impact on Long Term Renal Function.
ClinicalTrials.gov ID: NCT01936519
Acronym / sponsor ID: IRB 38115
Conditions: Immunosuppression, Renal Failure
Keywords: Everolimus, Zortress, Renal Function, Tacrolimus, Cyclosporine, Myfortic, Mycophenolic Acid, Liver Transplantation
Study type: Interventional
Recruitment status: Completed
Enrolment: 24 participants (actual)
Lead sponsor: Milton S. Hershey Medical CenterUniversity, hospital or other
Collaborators: Novartis Pharmaceuticals
Study start: 16 Dec 2013 (actual)
Primary completion: 31 Jul 2019 (actual)
Study completion: 31 Jul 2019 (actual)
First posted: 6 Sep 2013 (estimated)
Results: Posted 12 Jan 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This study will examine the renal sparing impact of implementing a strategy of conversion to everolimus from a calcineurin inhibitor based immunosuppressive protocol at 3 months post liver transplant

Detailed description

Arm A: Conversion to Everolimus immunosuppression combined with mycophenolic acid (Myfortic: MPA), and complete discontinuation of Calcineurin inhibitor at 3 months post transplant.

Arm B: Continuation with standard immunosuppressive therapy consisting of Calcineurin inhibitor associated with mycophenolic acid (Myfortic: MPA).

Follow up: 2 years.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Calcineurin Inhibitor with Mycophenolic Acid	Active comparator	Drug: Calcineurin InhibitorCalcineurin inhibitor immunosuppression with mycophenolic acid
Everolimus with Mycophenolic Acid	Experimental	Drug: Arm A: EverolimusConversion to Everolimus immunosuppression combined with mycophenolic acid (Myfortic: MPA), and complete discontinuation of Calcineurin inhibitor at 3 months post transplant.

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

Ability and willingness to provide written informed consent and adhere to study regimen.
Primary deceased donor liver transplant recipients 18-70 years of age
Functioning allograft at randomization (AST, ALT, Total Bilirubin levels ≤3 times ULN, and AlkP and GGT levels ≤ 5 times ULN). Elevated GGT alone, in combination with AST, ALT, total bilirubin and AlkP within defined range does not exclude patients from randomization.
Recipients on an immunosuppressive regimen of corticosteroids and tacrolimus.
Confirmed recipient HCV status at Screening (either by serology or PCR).

Key exclusion criteria (20 listed)

Recipients of multiple solid organ or islet cell tissue transplants, or have previously received an organ or tissue transplant. Combined liver kidney transplant recipients.
Living donor or split liver recipients.
History of malignancy of any organ system within past 5 years whether or not there is evidence of local recurrence or metastases, other than non-metastatic basal or squamous cell carcinoma of the skin or HCC.
Hepatocellular carcinoma that does not fulfill Milan criteria (1 nodule ≤ 5 cm, 2-3 nodules all < 3 cm, per explant histology of recipient liver.
Use of antibody induction therapy.

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 A: EverolimusAlso: Zortress; Mycophenolic Acid (Myfortic)Conversion to Everolimus immunosuppression combined with mycophenolic acid (Myfortic: MPA), and complete discontinuation of Calcineurin inhibitor at 3 months post transplant.	Drug	Everolimus with Mycophenolic Acid
Calcineurin InhibitorAlso: Tacrolimus (Prograf), Cyclosporine (Gengraf), Mycophenolic Acid (Myfortic)Comparison Arm: Continuation with standard immunosuppressive therapy consisting of Calcineurin inhibitor associated with mycophenolic acid (Myfortic: MPA).	Drug	Calcineurin Inhibitor with Mycophenolic Acid

Primary outcome

Renal Function as Measured by 24 Hour Urine Creatinine Clearance
Time frame: 6 months, 1 year, and 2 years
Renal Function was assessed by 24 hr urine collection creatinine clearance measured (mL/min). 24 Hr urine collection was assessed at baseline, 6 months, 1 year, and 2 years post transplant.
Renal Function as Measured by Serum Creatinine Level
Time frame: 6 months, 1 year, and 2 years
Serum creatinine levels were assessed at 6 months, 1 year, and 2 years post transplant
Renal Function as Measured by Cockcroft Gault Creatinine Clearance
Time frame: 6 months, 1 year, and 2 years
The Cockcroft-Gault formula for estimating creatinine clearance was determined at 6 months, 1 year, and 2 years post transplant
Renal Function as Measured by Modification of Diet in Renal Disease (MDRD) Estimated Glomerular Filtration Rate (eGFR)
Time frame: 6 months, 1 year, and 2 years
Modification of Diet in Renal Disease (MDRD) estimated Glomerular Filtration Rate (eGFR) was assessed at 6 months, 1 year, and 2 years post transplant.
Renal Function as Measured by Iothalamate Clearance
Time frame: 6 months, 1 year, and 2 years
Iothalamate Clearance was assessed at 6 months, 1 year, and 2 years post transplant.

Results and safety

Results posted to the registry on 12 Jan 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Calcineurin Inhibitor and Mycophenolic Acid	12	11
Everolimus and Mycophenolic Acid	12	8

Primary outcome: Renal Function as Measured by 24 Hour Urine Creatinine Clearance

Time frame: 6 months, 1 year, and 2 years. Mean (Standard Deviation). Unit: mL/min

Measure	Calcineurin Inhibitor With Mycophenolic Acid n = 11	Everolimus With Mycophenolic Acid n = 8
24hr Urine Creatinine Clearance at 6 months	68.09 (30.08)	70.75 (29.03)
24hr Urine Creatinine Clearance at 1 year	68.09 (28.91)	86.8 (29.34)
24hr Urine Creatinine Clearance at 2 years	61.54 (27.5)	90.63 (30.05)

Primary outcome: Renal Function as Measured by Serum Creatinine Level

Time frame: 6 months, 1 year, and 2 years. Mean (Standard Deviation). Unit: mg/dL

Measure	Calcineurin Inhibitor and Mycophenolic Acid n = 11	Everolimus and Mycophenolic Acid n = 8
Serum Creatinine at 6 months	1.29 (0.43)	1.02 (0.24)
Serum Creatinine at 1 year	1.29 (0.38)	0.95 (0.25)
Serum Creatinine at 2 years	1.51 (0.69)	0.95 (0.30)

Primary outcome: Renal Function as Measured by Cockcroft Gault Creatinine Clearance

Time frame: 6 months, 1 year, and 2 years. Mean (Standard Deviation). Unit: mL/min/1.73m2

Measure	Calcineurin Inhibitor and Mycophenolic Acid n = 11	Everolimus and Mycophenolic Acid n = 8
Cockcroft Gault Creatinine Clearance at 6 months	79.84 (29.29)	100.17 (45.39)
Cockcroft Gault Creatinine Clearance at 1 year	86.84 (37.17)	113.47 (60.76)
Cockcroft Gault Creatinine Clearance at 2 years	80.85 (28.57)	108.16 (60.1)

Calcineurin Inhibitor and Mycophenolic Acid vs Everolimus and Mycophenolic Acid: Mean Difference (Net): 27.32 (95% CI -16.17 to 70.80), p = 0.283, Wilcoxon (Mann-Whitney)

Primary outcome: Renal Function as Measured by Modification of Diet in Renal Disease (MDRD) Estimated Glomerular Filtration Rate (eGFR)

Time frame: 6 months, 1 year, and 2 years. Mean (Standard Deviation). Unit: mL/min/1.73 m2

Measure	Calcineurin Inhibitor and Mycophenolic Acid n = 11	Everolimus and Mycophenolic Acid n = 8
MDRD eGFR at 6 months	62.18 (22.51)	81.27 (31.30)
MDRD eGFR at 1 year	60.63 (19.68)	88.01 (34.08)
MDRD eGFR at 2 years	53.29 (17.58)	87.37 (32.09)

Calcineurin Inhibitor and Mycophenolic Acid vs Everolimus and Mycophenolic Acid: Median Difference (Final Values): 34.08 (95% CI 9.95 to 58.21), p = 0.013, Wilcoxon (Mann-Whitney)

Adverse events

Time frame: 2 years. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Calcineurin Inhibitor and Mycophenolic Acid	0 of 12 (0%)	12 of 12 (100%)	0 of 12
Everolimus and Mycophenolic Acid	1 of 12 (8.3%)	12 of 12 (100%)	0 of 12

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 19046932Burra P, Senzolo M, Masier A, Prestele H, Jones R, Samuel D, Villamil F. Factors influencing renal function after liver transplantation. Results from the MOST, an international observational study. Dig Liver Dis. 2009 May;41(5):350-6. doi: 10.1016/j.dld.2008.09.018. Epub 2008 Nov 28.
Background: PubMed 11773892Gonwa TA, Mai ML, Melton LB, Hays SR, Goldstein RM, Levy MF, Klintmalm GB. End-stage renal disease (ESRD) after orthotopic liver transplantation (OLTX) using calcineurin-based immunotherapy: risk of development and treatment. Transplantation. 2001 Dec 27;72(12):1934-9. doi: 10.1097/00007890-200112270-00012.
Background: PubMed 12954741Ojo AO, Held PJ, Port FK, Wolfe RA, Leichtman AB, Young EW, Arndorfer J, Christensen L, Merion RM. Chronic renal failure after transplantation of a nonrenal organ. N Engl J Med. 2003 Sep 4;349(10):931-40. doi: 10.1056/NEJMoa021744.
Background: PubMed 15084934Velidedeoglu E, Bloom RD, Crawford MD, Desai NM, Campos L, Abt PL, Markmann JW, Mange KC, Olthoff KM, Shaked A, Markmann JF. Early kidney dysfunction post liver transplantation predicts late chronic kidney disease. Transplantation. 2004 Feb 27;77(4):553-6. doi: 10.1097/01.tp.0000114609.99558.41.
Background: PubMed 19032225Wadei HM, Geiger XJ, Cortese C, Mai ML, Kramer DJ, Rosser BG, Keaveny AP, Willingham DL, Ahsan N, Gonwa TA. Kidney allocation to liver transplant candidates with renal failure of undetermined etiology: role of percutaneous renal biopsy. Am J Transplant. 2008 Dec;8(12):2618-26. doi: 10.1111/j.1600-6143.2008.02426.x.
Background: PubMed 15816874Randhawa PS, Shapiro R. Chronic renal failure after liver transplantation. Am J Transplant. 2005 May;5(5):967-8. doi: 10.1111/j.1600-6143.2005.00819.x. No abstract available.
Background: PubMed 2362625McCauley J, Van Thiel DH, Starzl TE, Puschett JB. Acute and chronic renal failure in liver transplantation. Nephron. 1990;55(2):121-8. doi: 10.1159/000185938.
Background: PubMed 9679823Fisher NC, Nightingale PG, Gunson BK, Lipkin GW, Neuberger JM. Chronic renal failure following liver transplantation: a retrospective analysis. Transplantation. 1998 Jul 15;66(1):59-66. doi: 10.1097/00007890-199807150-00010.
Background: PubMed 19120077Neuberger JM, Mamelok RD, Neuhaus P, Pirenne J, Samuel D, Isoniemi H, Rostaing L, Rimola A, Marshall S, Mayer AD; ReSpECT Study Group. Delayed introduction of reduced-dose tacrolimus, and renal function in liver transplantation: the 'ReSpECT' study. Am J Transplant. 2009 Feb;9(2):327-36. doi: 10.1111/j.1600-6143.2008.02493.x. Epub 2008 Dec 15.
Background: PubMed 15059040Chapman TM, Perry CM. Everolimus. Drugs. 2004;64(8):861-72; discussion 873-4. doi: 10.2165/00003495-200464080-00005.
Background: PubMed 16598777Levy G, Schmidli H, Punch J, Tuttle-Newhall E, Mayer D, Neuhaus P, Samuel D, Nashan B, Klempnauer J, Langnas A, Calmus Y, Rogiers X, Abecassis M, Freeman R, Sloof M, Roberts J, Fischer L. Safety, tolerability, and efficacy of everolimus in de novo liver transplant recipients: 12- and 36-month results. Liver Transpl. 2006 Nov;12(11):1640-8. doi: 10.1002/lt.20707.
Background: PubMed 11805723Nashan B. Early clinical experience with a novel rapamycin derivative. Ther Drug Monit. 2002 Feb;24(1):53-8. doi: 10.1097/00007691-200202000-00010.
Individual participant dataSharing planned: Yes. Plan to publish de-identified data

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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.

Zakiyah Kadry, MD principal investigator

Penn State College of Medicine; Penn State Milton S Hershey Medical Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Arm A: Everolimus and Calcineurin Inhibitor in people with Immunosuppression and Renal Failure, run by Milton S. Hershey Medical Center 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 29 Jan 2021. 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.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Jan 2021). 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 as Measured by 24 Hour Urine Creatinine Clearance (time frame: 6 months, 1 year, and 2 years). The study lists 5 primary outcomes in all. 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 NCT01936519, which also lists 29 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 29 Jan 2021.