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Certican® (Everolimus) Against Cytomegalovirus Disease in Renal Transplant Patients (Certi-CMV)

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ClinicalTrials.gov Identifier: NCT00828503
Recruitment Status : Unknown
Verified August 2012 by Marcus Saemann, Medical University of Vienna.
Recruitment status was:  Recruiting
First Posted : January 26, 2009
Last Update Posted : September 3, 2012
Sponsor:
Information provided by (Responsible Party):
Marcus Saemann, Medical University of Vienna

Tracking Information
First Submitted Date  ICMJE January 23, 2009
First Posted Date  ICMJE January 26, 2009
Last Update Posted Date September 3, 2012
Study Start Date  ICMJE December 2008
Estimated Primary Completion Date December 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 23, 2009)
relative changes in CMV-load (copies/mL), as determined by qCMV-PCR from whole blood throughout the observational period [ Time Frame: 2 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT00828503 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 23, 2009)
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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Certican® (Everolimus) Against Cytomegalovirus Disease in Renal Transplant Patients
Official Title  ICMJE Certican® (Everolimus) Against Cytomegalovirus Disease in Renal Transplant Patients
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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Cytomegalovirus Disease
Intervention  ICMJE
  • Drug: Certican (everolimus) + valganciclovir

    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)

  • Drug: Valganciclovir
    Valganciclovir (or ganciclovir) will be administered alone (valganciclovir: 450 mg twice daily, ganciclovir 5 mg/kg i.v. twice daily)
Study Arms  ICMJE
  • Active Comparator: 1 Certican + Valganciclovir
    Valganciclovir will be administered and Certican (everolimus) will be added as immunosuppression
    Intervention: Drug: Certican (everolimus) + valganciclovir
  • Active Comparator: 2 Valganciclovir alone
    Valganciclovir will be added alone.
    Intervention: Drug: Valganciclovir
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: January 23, 2009)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2014
Estimated Primary Completion Date December 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00828503
Other Study ID Numbers  ICMJE EudraCT: 2008-004745-28
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Marcus Saemann, Medical University of Vienna
Study Sponsor  ICMJE Marcus Saemann
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Sabine Schmaldienst, MD Medical University of Vienna
PRS Account Medical University of Vienna
Verification Date August 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP