Graft DysfunctionPhase 4NCT02096107

Novartis Everolimus Transition

A Phase 4 study testing Everolimus in people with Graft Dysfunction and Interstitial Fibrosis, run by Medical University of South Carolina 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

Search all trials

Trial summary

Transition from tacrolimus based triple therapy with Mycophenolate Mofetil (MMF) and steroids in stable renal transplant patients to low intensity tacrolimus, everolimus and prednisone will be associated with improvement in Glomular Filtration Rate (GFR) and allograft fibrosis. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Graft Dysfunction, Interstitial Fibrosis
What is being tested?: Everolimus
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 60 participants
Where: 1 siteUnited States
Study dates: Feb 2014to May 2017
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

At least 18 years of age and able to give informed consent.
Received a first or repeat cadaveric (including ECD) or living donor renal transplant.
Patient has stable graft function, defined as no change of greater than 40% of baseline serum creatinine and no acute rejection during the past month.
Currently receiving tacrolimus, mycophenolate mofetil and prednisone as their immunosuppression regimen

Who cannot join

Biopsy proven acute rejection episode that occurred within the past month.
Malignancy within the past 3 years, except for non-melanoma skin cancer.
Currently enrolled in an investigational drug trial.
Woman of child bearing potential not utilizing an effective form of birth control.
Patients with uncontrolled dyslipidemia, defined at serum fasting LDL >200 mg/dL or serum fasting triglycerides >500 mg/dL.
Patients with a spot urine protein to creatinine ratio of > 800 mg of protein per gram of creatinine.

Show all 10Show fewer

WBC < 2,000 cells/mm3
Platelets < 75,000 cells/mm3
Patients who have received an organ transplant other than a kidney.
Patients with a history of biopsy proven FSGS, MPGN, or PGN.

Trial locations and contacts

1 site in 1 country.

United States1 site

Medical University of South Carolina
Charleston, South Carolina, 29425

Other trials in United States

About this study

Official title: Safety and Efficacy of Everolimus Transition in Minimizing Progressive Graft Dysfunction and Interstitial Fibrosis in Adult Kidney Transplant Recipients

Conditions: Graft Dysfunction, Interstitial Fibrosis
Being tested: Everolimus, Standard of Care
Keywords: Everolimus, Graft dysfunction, Interstitial fibrosis
Medical subject headings: Pulmonary Fibrosis

What participants receive

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

EverolimusDrug
Convert mycophenolate to everolimus with subsequent reduction in exposure to tacrolimus
Standard of CareOther
Tacrolimus, mycophenolate mofetil and steroids

Study groups in NCT02096107
Study group	Role	What they receive
Low intensity Tacrolimus	Active comparator	Low tacrolimus, everolimus, and steroids Receives: Drug: Everolimus
Standard of Care	Other	Tacrolimus, mycophenolate mofetil and steroids Receives: Other: Standard of Care

What is being measured

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

Kidney Allograft Fibrosis Assessment
Measure and compare the change in interstitial fibrosis (morphometric analysis of trichrome stained slides) at one-year post-transplant in patients converted to everolimus, low intensity tacrolimus and prednisone versus the standard of care tacrolimus, mycophenolate and prednisone regimen.
The scale is a percentage of the tissue that demonstrates fibrosis. The scale range is 0 to 100%. The higher the percentage, the worse the fibrosis and the poorer the prognosis. A lower score (percentage) is therefore better.
Measured: 1 year

Secondary outcomes (5)

Renal Function Measured by Estimated Glomerular Filtration Rate (eGFR)
Measure and compare the estimated GFR (using the 4-variable modified MDRD equation) in patients converted to everolimus, low intensity tacrolimus and prednisone versus the standard of care tacrolimus, mycophenolate and prednisone regimen, both at one year and two years post-transplant.
Measured: 1 year
Kidney Allograft Survival
Compare the patient and graft survival rates at one-year post-transplant in each group.
Measured: 1 year
Percentage of Participants Discontinuing or Modifying Immunosuppressant Use
Measure and compare the rates of immunosuppressant discontinuation and modification for each group.
Measured: 2 year
Adverse Drug Reactions
Measure and compare the incidence of significant immunosuppressant-related adverse drug reactions for each group.
Measured: 2 year
Infection
Compare the rates of post-transplant infections, including CMV, BK, and admissions to the hospital for infectious causes in each group.
Measured: 2 year

Timeline

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

Feb 2014May 2017

First posted26 Mar 2014 (estimated)
Study startFeb 2014
Primary completionMay 2017
Study completionMay 2017

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 (1)Papers the sponsor has linked to this study.
Other trials for Graft DysfunctionStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 60 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02096107
Sponsor's protocol ID: Pro00030099
Status last verified: Jul 2018
First submitted: 28 Feb 2014
Last updated: 8 Aug 2018
Results posted: Yes, on ClinicalTrials.gov

Publications

Taber DJ, Chokkalingam A, Su Z, Self S, Miller D, Srinivas T. Randomized controlled trial assessing the impact of everolimus and low-exposure tacrolimus on graft outcomes in kidney transplant recipients. Clin Transplant. 2019 Oct;33(10):e13679. doi: 10.1111/ctr.13679. Epub 2019 Sep 12.
PubMed 31365151

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?

See locations

Recruiting
Avoiding Recooling After Normothermic Machine Perfusion in Liver Transplantation
Liver Transplantation (LT), Ischemia-Reperfusion Injury
Not yet recruitingObservational study
Preoperative Gastric Ultrasound and Left Ventricular Function in Coronary Artery Bypass Surgery
Coronary Artery Disease, Left Ventricular Systolic Dysfunction
Active, not recruitingPhase 2
Autologous Serum Obtained by a Closed-Circuit Collection Device
GVHD, Meibomian Gland Dysfunction (Disorder)
Active, not recruitingEarly Phase 1
Haploidentical Transplant for People With Chronic Granulomatous Disease (CGD) Using Alemtuzumab, Busulfan and TBI With Post-Transplant Cyclophosphamide
Chronic Granulomatous Disease
RecruitingObservational study
Evaluation of Patients With Immune Function Abnormalities
Chronic Granulomatous Disease (CGD), X-Linked Severe Combined Immune Deficiency (XSCID)

All Graft Dysfunction trials

Study at a glance

From the registry record, last updated by the sponsor on 8 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Safety and Efficacy of Everolimus Transition in Minimizing Progressive Graft Dysfunction and Interstitial Fibrosis in Adult Kidney Transplant Recipients
ClinicalTrials.gov ID: NCT02096107
Acronym / sponsor ID: Pro00030099
Conditions: Graft Dysfunction, Interstitial Fibrosis
Keywords: Everolimus, Graft dysfunction, Interstitial fibrosis
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 60 participants (actual)
Lead sponsor: Medical University of South CarolinaUniversity, hospital or other
Collaborators: Novartis
Study start: Feb 2014 (actual)
Primary completion: May 2017 (actual)
Study completion: May 2017 (actual)
First posted: 26 Mar 2014 (estimated)
Results: Posted 8 Aug 2018

Clinical summary

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

Study design

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

Arm	Type	Receives
Low intensity Tacrolimus	Active comparator	Drug: EverolimusLow tacrolimus, everolimus, and steroids
Standard of Care	Other	Other: Standard of CareTacrolimus, mycophenolate mofetil and steroids

Who may qualify

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

Key inclusion criteria (4 listed)

At least 18 years of age and able to give informed consent.
Received a first or repeat cadaveric (including ECD) or living donor renal transplant.
Patient has stable graft function, defined as no change of greater than 40% of baseline serum creatinine and no acute rejection during the past month.
Currently receiving tacrolimus, mycophenolate mofetil and prednisone as their immunosuppression regimen

Key exclusion criteria (10 listed)

Biopsy proven acute rejection episode that occurred within the past month.
Malignancy within the past 3 years, except for non-melanoma skin cancer.
Currently enrolled in an investigational drug trial.
Woman of child bearing potential not utilizing an effective form of birth control.
Patients with uncontrolled dyslipidemia, defined at serum fasting LDL >200 mg/dL or serum fasting triglycerides >500 mg/dL.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
EverolimusConvert mycophenolate to everolimus with subsequent reduction in exposure to tacrolimus	Drug	Low intensity Tacrolimus
Standard of CareTacrolimus, mycophenolate mofetil and steroids	Other	Standard of Care

Primary outcome

Kidney Allograft Fibrosis Assessment
Time frame: 1 year
Measure and compare the change in interstitial fibrosis (morphometric analysis of trichrome stained slides) at one-year post-transplant in patients converted to everolimus, low intensity tacrolimus and prednisone versus the standard of care tacrolimus, mycophenolate and prednisone regimen. The scale is a percentage of the tissue that demonstrates fibrosis. The scale range is 0 to 100%. The higher the percentage, the worse the fibrosis and the poorer the prognosis. A lower score (percentage) is therefore better.

5 secondary outcomes

Renal Function Measured by Estimated Glomerular Filtration Rate (eGFR)
Time frame: 1 year
Kidney Allograft Survival
Time frame: 1 year
Percentage of Participants Discontinuing or Modifying Immunosuppressant Use
Time frame: 2 year
Adverse Drug Reactions
Time frame: 2 year
Infection
Time frame: 2 year

Results and safety

Results posted to the registry on 8 Aug 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Low Intensity Tacrolimus	30	30
Standard of Care	30	30

Primary outcome: Kidney Allograft Fibrosis Assessment

Time frame: 1 year. Mean (Inter-Quartile Range). Unit: % of fibrosis

Measure	Low Intensity Tacrolimus n = 15	Standard of Care n = 15
Baseline	22.9 (17.9 to 25.7)	20.8 (18.4 to 30.4)
End of Follow-up	22.9 (18.6 to 28.1)	27.8 (18.7 to 31.0)

Population analysed: The number of subjects analyzed for the fibrosis assessment was 15 in each group, because biopsy samples for both baseline and end of follow-up were only able to be obtained from 15 subjects per group.

5 secondary outcomes are reported in the full results.

Adverse events

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

Group	Serious adverse events	Other adverse events	Deaths
Low Intensity Tacrolimus	8 of 30 (26.7%)	11 of 30 (36.7%)	0 of 30
Standard of Care	6 of 30 (20%)	6 of 30 (20%)	0 of 30

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Aug 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 31365151Taber DJ, Chokkalingam A, Su Z, Self S, Miller D, Srinivas T. Randomized controlled trial assessing the impact of everolimus and low-exposure tacrolimus on graft outcomes in kidney transplant recipients. Clin Transplant. 2019 Oct;33(10):e13679. doi: 10.1111/ctr.13679. Epub 2019 Sep 12.

Related trials for Graft Dysfunction

Recruiting
Avoiding Recooling After Normothermic Machine Perfusion in Liver Transplantation
Liver Transplantation (LT), Ischemia-Reperfusion Injury
Not yet recruitingObservational study
Preoperative Gastric Ultrasound and Left Ventricular Function in Coronary Artery Bypass Surgery
Coronary Artery Disease, Left Ventricular Systolic Dysfunction
Active, not recruitingPhase 2
Autologous Serum Obtained by a Closed-Circuit Collection Device
GVHD, Meibomian Gland Dysfunction (Disorder)
Active, not recruitingEarly Phase 1
Haploidentical Transplant for People With Chronic Granulomatous Disease (CGD) Using Alemtuzumab, Busulfan and TBI With Post-Transplant Cyclophosphamide
Chronic Granulomatous Disease
RecruitingObservational study
Evaluation of Patients With Immune Function Abnormalities
Chronic Granulomatous Disease (CGD), X-Linked Severe Combined Immune Deficiency (XSCID)

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.

Titte Srinivas, MD principal investigator

Medical University of South Carolina

David Taber principal investigator

Medical University of South Carolina, Department of Surgery

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 Everolimus in people with Graft Dysfunction and Interstitial Fibrosis, run by Medical University of South Carolina 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 10 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 8 Aug 2018. 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 8 Aug 2018). 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?

Kidney Allograft Fibrosis Assessment (time frame: 1 year). 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 NCT02096107, which also lists 1 linked publication.

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 8 Aug 2018.