Certican® (Everolimus) Against Cytomegalovirus Disease in Renal Transplant Patients (Certi-CMV)
Primary Purpose
Cytomegalovirus Disease
Status
Unknown status
Phase
Phase 2
Locations
Austria
Study Type
Interventional
Intervention
Certican (everolimus) + valganciclovir
Valganciclovir
Sponsored by
About this trial
This is an interventional treatment trial for Cytomegalovirus Disease focused on measuring Certi-CMV, immunosuppressive switch (to Certican), renal transplant
Eligibility Criteria
Inclusion Criteria:
CMV-disease after renal transplantation, i.e.,(1.) CMV present in the blood, and (2.) one of the following symptoms (for viral syndrome, from the American Society of Transplantation recommendations for use in clinical trials1):
- body temperature ≥ 38°C
- new or increased significant malaise
- leucopenia (< 3500/mL)
- atypical lymphocytosis ≥ 5%
- thrombocytopenia (platelets < 100.000/mL)
- no other cause of symptoms/signs identified
- informed consent of the patient
Exclusion Criteria:
- patients with a known hypersensitivity to everolimus, sirolimus or any of the excipients
- administration of strong CYP3A4 Inhibitors (e.g. ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin) and inducers (rifampicin), unless the benefit outweighs the risk, according to the judgment of the clinical investigator
- acute rejection episodes in the first 3 months after renal transplantation
- active hepatitis in the previous month
- Significant proteinuria (> 0.8g/24h Urine)
- hepatic impairment, according to the criteria defined by Bénichou et al.2: a singular elevation of GPT or conjugated bilirubin to a value twice above the normal level, or a combined elevation of GOT, AP, and total bilirubin, given that at least one parameter is twice above the normal level
- hematocrit < 25%
- any significant wound healing disorder (anamnestic)
- blood white blood cell (WBC) count < 3000/mL
- platelets < 50.000/mL
- severe dyslipidemia (cholesterol >300mg/dL, triglycerides > 350mg/dL)
- uncontrolled hypertension (continuous episodes of hypertension above 140/90 (WHO classification and American Society of Transplantation recommendations 3) despite adequate hypertensive therapy)
- uncontrolled hyperuricemia (uric acid > 8mg/dL)
- pregnancy
- any immunosuppressive protocol which does not allow the addition of Certican®, according to the judgment of the clinical investigator
Sites / Locations
- Medical University of ViennaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
1 Certican + Valganciclovir
2 Valganciclovir alone
Arm Description
Valganciclovir will be administered and Certican (everolimus) will be added as immunosuppression
Valganciclovir will be added alone.
Outcomes
Primary Outcome Measures
relative changes in CMV-load (copies/mL), as determined by qCMV-PCR from whole blood throughout the observational period
Secondary Outcome Measures
CMV-load (copies/mL) after 1-8 weeks, in months 3, 4, 6 and 12; Time (in weeks) until the CMV-load reaches ≤600 copies/mL
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00828503
Brief Title
Certican® (Everolimus) Against Cytomegalovirus Disease in Renal Transplant Patients
Acronym
Certi-CMV
Official Title
Certican® (Everolimus) Against Cytomegalovirus Disease in Renal Transplant Patients
Study Type
Interventional
2. Study Status
Record Verification Date
August 2012
Overall Recruitment Status
Unknown status
Study Start Date
December 2008 (undefined)
Primary Completion Date
December 2013 (Anticipated)
Study Completion Date
June 2014 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Marcus Saemann
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
A prospective, randomized safety and efficacy study of Certican® as add-on therapy against CMV disease in renal transplant recipients
OBJECTIVES:
Primary Objective:
To demonstrate efficacy of Certican® as add-on therapy against CMV disease in comparison to either valcyte® (valganciclovir) or cymevene® (ganciclovir) alone, evaluated by quantitative measurement of CMV-DNA with PCR from the blood (qCMV-PCR)
Secondary Objectives:
To assess safety and tolerability of Certican® in patients with CMV- disease To study the effects of Certican® treatment on quality of life
Detailed Description
DESIGN / PHASE Prospective, single-center, randomized, parallel group, controlled, phase II study.
PATIENTS / GROUPS 40 patients in 2 groups 20 patients per group Randomization ratio 1:1, no stratification
INVESTIGATIONAL DRUG Oral MED 1: Certican® initial dose: 1,5-3 mg day target trough level: 3-8 ng/mL (first levels will be performed after 3 days and then adjusted until - according to the judgment of the clinical investigator - a stable degree of immunosuppression is reached; thereafter Certican® trough levels will be performed at the scheduled appointments)
COMPARATIVE DRUG No therapy (add-on design
CONCOMITANT MEDICATION Allowed The concomitant immunosuppressive medication will be adjusted to the additional administration of Certican®. For example, if the patient already receives cyclosporine A or tacrolimus, this will be adjusted, according to the current recommendations4 at the judgment of the clinical investigator
TOLERABILITY / SAFETY ENDPOINTS:
Rejection Hematocrit Platelet count WBC count Wound healing disorders Blood lipids (cholesterol, triglycerides) Infections (other than CMV)
PHARMACOKINETIC / PHARMACODYNAMIC ENDPOINTS Certican® (everolimus) trough levels
STATISTICAL METHODOLOGY Primary Endpoint: CMV-load (copies/mL)
Null and alternative hypotheses:
H0 Treatment with Certican® (everolimus) in combination with valcyte® (valganciclovir) or cymevene® (ganciclovir) is equal to valcyte® (valganciclovir) or cymevene® (ganciclovir) alone in reducing the CMV-load in renal transplant patients with CMV-disease H1: Treatment with Certican® (everolimus) in combination with valcyte® (valganciclovir) or cymevene® (ganciclovir) is superior to valcyte® (valganciclovir) or cymevene® (ganciclovir) in reducing CMV load (copies/mL) in renal transplant patients with CMV-disease Type-I and -II errors - power. α=0.05 ß=0.2 (power 0.8) Statistical methodology ANOVA of repeated measures (CMV-copies/mL), one-sided t-test of CMV load at distinct time-points, one-sided t-test of the time (in weeks) until CMV-load reaches ≤600 copies/mL Sample size calculation Based on a one-sided testing and a σ of 0.2 in relative changes of CMV-copies, an α=0.05 And a ß=0.2 a sample size of 20 patients per group was determined. Main analysis set Per-protocol (efficacy) and intention to treat (ITT) for safety Other endpoints Bonferroni corrected t-tests will be performed for CMV-copies/mL at each time point of the follow-up period. The time to copies ≤ 600 will also be analyzed by a t-test. All other secondary endpoints and subgroup analysis will be performed in explorative intention (descriptive statistics).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cytomegalovirus Disease
Keywords
Certi-CMV, immunosuppressive switch (to Certican), renal transplant
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
1 Certican + Valganciclovir
Arm Type
Active Comparator
Arm Description
Valganciclovir will be administered and Certican (everolimus) will be added as immunosuppression
Arm Title
2 Valganciclovir alone
Arm Type
Active Comparator
Arm Description
Valganciclovir will be added alone.
Intervention Type
Drug
Intervention Name(s)
Certican (everolimus) + valganciclovir
Intervention Description
Oral MED 1: Certican® initial dose: 1,5-3 mg day target trough level: 3-8 ng/mL (first levels will be performed after 3 days and then adjusted until - according to the judgement of the clinical investigator - a stable degree of immunosuppression is reached; thereafter Certican® trough levels will be performed at the scheduled appointments)
MED 2: Valganciclovir (or ganciclovir) will be administered in addition to Certican (valganciclovir: 450 mg twice daily, ganciclovir 5 mg/kg i.v. twice daily)
Intervention Type
Drug
Intervention Name(s)
Valganciclovir
Intervention Description
Valganciclovir (or ganciclovir) will be administered alone (valganciclovir: 450 mg twice daily, ganciclovir 5 mg/kg i.v. twice daily)
Primary Outcome Measure Information:
Title
relative changes in CMV-load (copies/mL), as determined by qCMV-PCR from whole blood throughout the observational period
Time Frame
2 years
Secondary Outcome Measure Information:
Title
CMV-load (copies/mL) after 1-8 weeks, in months 3, 4, 6 and 12; Time (in weeks) until the CMV-load reaches ≤600 copies/mL
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
CMV-disease after renal transplantation, i.e.,(1.) CMV present in the blood, and (2.) one of the following symptoms (for viral syndrome, from the American Society of Transplantation recommendations for use in clinical trials1):
body temperature ≥ 38°C
new or increased significant malaise
leucopenia (< 3500/mL)
atypical lymphocytosis ≥ 5%
thrombocytopenia (platelets < 100.000/mL)
no other cause of symptoms/signs identified
informed consent of the patient
Exclusion Criteria:
patients with a known hypersensitivity to everolimus, sirolimus or any of the excipients
administration of strong CYP3A4 Inhibitors (e.g. ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin) and inducers (rifampicin), unless the benefit outweighs the risk, according to the judgment of the clinical investigator
acute rejection episodes in the first 3 months after renal transplantation
active hepatitis in the previous month
Significant proteinuria (> 0.8g/24h Urine)
hepatic impairment, according to the criteria defined by Bénichou et al.2: a singular elevation of GPT or conjugated bilirubin to a value twice above the normal level, or a combined elevation of GOT, AP, and total bilirubin, given that at least one parameter is twice above the normal level
hematocrit < 25%
any significant wound healing disorder (anamnestic)
blood white blood cell (WBC) count < 3000/mL
platelets < 50.000/mL
severe dyslipidemia (cholesterol >300mg/dL, triglycerides > 350mg/dL)
uncontrolled hypertension (continuous episodes of hypertension above 140/90 (WHO classification and American Society of Transplantation recommendations 3) despite adequate hypertensive therapy)
uncontrolled hyperuricemia (uric acid > 8mg/dL)
pregnancy
any immunosuppressive protocol which does not allow the addition of Certican®, according to the judgment of the clinical investigator
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Marcus D Säemann, MD
Phone
+431404005593
Email
marcus.saemann@meduniwien.ac.at
First Name & Middle Initial & Last Name or Official Title & Degree
Manfred Hecking, MD
Phone
+431404005593
Email
manfred.hecking@meduniwien.ac.at
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sabine Schmaldienst, MD
Organizational Affiliation
Medical University of Vienna
Official's Role
Study Chair
Facility Information:
Facility Name
Medical University of Vienna
City
Vienna
ZIP/Postal Code
1090
Country
Austria
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Manfred Hecking, MD
12. IPD Sharing Statement
Citations:
PubMed Identifier
16426310
Citation
Humar A, Michaels M; AST ID Working Group on Infectious Disease Monitoring. American Society of Transplantation recommendations for screening, monitoring and reporting of infectious complications in immunosuppression trials in recipients of organ transplantation. Am J Transplant. 2006 Feb;6(2):262-74. doi: 10.1111/j.1600-6143.2005.01207.x.
Results Reference
background
PubMed Identifier
2254635
Citation
Benichou C. Criteria of drug-induced liver disorders. Report of an international consensus meeting. J Hepatol. 1990 Sep;11(2):272-6. doi: 10.1016/0168-8278(90)90124-a.
Results Reference
background
PubMed Identifier
11044969
Citation
Kasiske BL, Vazquez MA, Harmon WE, Brown RS, Danovitch GM, Gaston RS, Roth D, Scandling JD, Singer GG. Recommendations for the outpatient surveillance of renal transplant recipients. American Society of Transplantation. J Am Soc Nephrol. 2000 Oct;11 Suppl 15:S1-86.
Results Reference
background
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Certican® (Everolimus) Against Cytomegalovirus Disease in Renal Transplant Patients
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