Phase 4
N=2,037
Advancing Renal TRANSplant eFficacy and Safety Outcomes With an eveRolimus-based regiMen (TRANSFORM)
End Stage Renal Disease (ESRD) · Chronic Kidney Disease (CKD) · Hemodialysis · Renal Replacement Therapy · Renal Transplantation
Bottom Line
View on ClinicalTrials.gov: NCT01950819 ↗Enrolled (actual)
2,037
Serious AEs
59.5%
Results posted
Jan 2019
Primary outcome: Primary: Incidence of Failure on the Composite of Treated Biopsy-proven Acute Rejection (tBPAR) or Estimated Glomerular Filtration Rate (eGFR) < 50 mL/Min/1.73m2. — 489; 456; 489; 443 Participants — p=0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 4
- Interventions
- Induction therapy (Biological); Corticosteroids (Drug); EVR+rCNI (Drug); MPA+sCNI (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- Feb 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Incidence of Failure on the Composite of Treated Biopsy-proven Acute Rejection (tBPAR) or Estimated Glomerular Filtration Rate (eGFR) < 50 mL/Min/1.73m2. |
489; 456; 489; 443 | 0.001 sig |
| SECONDARY Incidence of Failure on the Composite of (Treated Biopsy Proven Acute Rejection (tBPAR), Graft Loss or Death |
146; 131; 169; 147 | — |
| SECONDARY Incidence of Failure on the Composite Endpoint of tBPAR, Graft Loss, Death or eGFR < 50 mL/Min/1.73m2 |
497; 466; 497; 457 | — |
| SECONDARY Incidence of Failure on the Composite Endpoint of Graft Loss or Death. |
51; 54; 67; 65 | — |
| SECONDARY Incidence of Death, Graft Loss, tBPAR, BPAR, tAR, AR and Humoral Rejection |
20; 28; 32; 36; 33; 28 | — |
| SECONDARY Incidence of eGFR < 50 mL/Min/1.73m2 |
456; 424; 474; 423 | — |
| SECONDARY Renal Allograft Function : Mean Estimated Glomerular Filtration Rate, eGFR |
53.13; 52.25; 53.29; 54.49; 52.63; 54.91 | — |
| SECONDARY Evolution of Renal Function, as eGFR, Over Time by Slope Analysis. |
0.0001; 0.0047 | — |
| SECONDARY Renal Function Assessed by Creatinine Lab Values |
590.1; 601.8; 129.8; 128.6; 130.1; 127.6 | — |
| SECONDARY Renal Function by Alternative Formulae (e.g. CKD-EPI). eGFR Values Reported |
21.38; 20.10; 50.08; 52.00; 49.86; 52.75 | — |
| SECONDARY Incidence of Adverse Events, Serious Adverse Events and Adverse Events Leading to Study Regimen Discontinuation. |
276; 152 | — |
| SECONDARY Incidence of Cytomegalovirus and BK Virus, New Onset Diabetes Mellitus, Chronic Kidney Disease With Associated Proteinuria and Calcineurin Inhibitor Associated Adverse Events. |
53; 132; 103; 154; 144; 138 | — |
| SECONDARY Urinary Protein and Albumin Excretion by Treatment Estimated by Urinary Protein/Creatinine and Urinary Albumin/Creatinine Ratios. |
1019.75; 646.111; 150.061; 111.322; 149.049; 116.618 | — |
| SECONDARY Incidence of Major Cardiovascular Events. |
66; 86 | — |
| SECONDARY Incidence of Malignancies. |
41; 39 | — |
| SECONDARY Incidence of Failure on the Composite of Treated Biopsy-proven Acute Rejection (tBPAR) or Estimated Glomerular Filtration Rate (eGFR) < 50 mL/Min/1.73m2 Among Compliant Subjects. |
60; 106; 62; 102 | — |
| SECONDARY Incidence tBPAR (Treated Biopsy-proven Acute Rejection) by Severity and Time to Event (Participants) |
25; 18; 34; 36; 23; 17 | — |
| SECONDARY Incidence tBPAR (Treated Biopsy-proven Acute Rejection) by Severity and Time to Event (Events) |
146; 116; 72; 63; 24; 14 | — |
| SECONDARY Incidence of tBPAR (Treated Biopsy-proven Acute Rejection) Excluding Grade IA Rejections |
66; 53; 74; 55 | — |
| SECONDARY Incidence of Composite of tBPAR (Treated Biopsy-proven Acute Rejection)or eGRF<50 mL/Min/1.73m2 by Subgroup |
489; 456; 489; 443 | — |
| SECONDARY Incidence of tBPAR (Excluding Grade IA Rejections) or GFR<50 mL/Min/1.73m2 |
475; 441; 475; 426 | — |
| SECONDARY Incidence of Failure on the Composite of (Treated Biopsy Proven Acute Rejection (tBPAR), Graft Loss or Death or Loss to Follow-up |
181; 170; 218; 201 | — |
Summary
This is a 2-year, randomized, multicenter, open-label, 2-arm study evaluating the graft function of everolimus and reduced CNI versus MPA and standard CNI in adult de novo renal transplant recipients.
Eligibility Criteria
Inclusion Criteria
- Written informed consent obtained.
- Subject randomized within 24 hr of completion of transplant surgery.
- Recipient of a kidney with a cold ischemia time < 30 hours.
- Recipient of a primary (or secondary, if first graft is not lost due to immunological reasons) renal transplant from a deceased heart beating, living unrelated, living related non-human leukocyte antigen identical or an expanded criteria donor.
Exclusion Criteria
- Subject unable to tolerate oral medication at time of randomization.
- Use of other investigational drugs at the time of enrollment.
- History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes.
- Multi-organ transplant recipient.
- Recipient of ABO incompatible allograft or complement-dependent lymphocytotoxic (CDC) crossmatch positive transplant.
- Subject at high immunological risk for rejection as determined by local practice for assessment of anti-donor reactivity e.g. high PRA, presence of pre-existing DSA.
- Subject who is HIV-positive.
- HBsAg and/or a HCV positive subject with evidence of elevated LFTs (ALT/AST levels ≥ 2.5 times ULN). Viral serology results obtained within 6 months prior to randomization are acceptable.
- Recipient of a kidney from a donor who tests positive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus (HCV).
- Subject with a BMI greater than 35.
- Subject with severe systemic infections, current or within the two weeks prior to randomization.
- Subject requiring systemic anticoagulation.
- History of malignancy of any organ system.
- Subject with severe restrictive or obstructive pulmonary disorders.
- Subject with severe hypercholesterolemia or hypertriglyceridemia that cannot be controlled.
- Subject with white blood cell (WBC) count ≤ 2,000 /mm3 or with platelet count ≤ 50,000 /mm3.
- Pregnant or nursing (lactating) women.
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment.
Data sourced from ClinicalTrials.gov (NCT01950819). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.