Cytomegalovirus DiseasePhase 2Certi-CMVNCT00828503
Certican® (Everolimus) Against Cytomegalovirus Disease in Renal Transplant Patients
A Phase 2 study testing Certican (everolimus) + valganciclovir and Valganciclovir in people with Cytomegalovirus Disease, run by Marcus Saemann at 1 site in Austria.
Trial 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)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cytomegalovirus Disease
- What is being tested?
- Certican (everolimus) + valganciclovir and Valganciclovir
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteAustria
- Study dates
- Dec 2008to Jun 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
Austria1 site, 1 recruiting
- Recruiting
Medical University of Vienna
Vienna, Austria, 1090
Manfred Hecking, MD
About this study
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
Read the 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).
- Conditions
- Cytomegalovirus Disease
- Being tested
- Certican (everolimus) + valganciclovir, Valganciclovir
- Keywords
- Certi-CMV, immunosuppressive switch (to Certican), renal transplant
- Medical subject headings
- Cytomegalovirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Certican (everolimus) + valganciclovirDrug
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)
ValganciclovirDrug
Valganciclovir (or ganciclovir) will be administered alone (valganciclovir: 450 mg twice daily, ganciclovir 5 mg/kg i.v. twice daily)
| Study group | Role | What they receive |
|---|---|---|
| 1 Certican + Valganciclovir | Active comparator | Valganciclovir will be administered and Certican (everolimus) will be added as immunosuppression Receives: Drug: Certican (everolimus) + valganciclovir |
| 2 Valganciclovir alone | Active comparator | Valganciclovir will be added alone. Receives: Drug: Valganciclovir |
What is being measured
The primary outcome is the main question the study is designed to answer.
relative changes in CMV-load (copies/mL), as determined by qCMV-PCR from whole blood throughout the observational period
Measured: 2 years
Secondary outcomes (1)
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
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2009 (estimated)
- Study startDec 2008
- Primary completionDec 2013 (estimated)
- Study completionJun 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Cytomegalovirus DiseaseStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Marcus Saemann
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Marcus Saemann, Medical University of Vienna
- Investigators
- Sabine Schmaldienst, MD, Study chair, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00828503
- Sponsor's protocol ID
- EudraCT: 2008-004745-28
- Acronym
- Certi-CMV
- Status last verified
- Aug 2012
- First submitted
- 23 Jan 2009
- Last updated
- 3 Sep 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 16426310Benichou 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.
PubMed 2254635Kasiske 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.
PubMed 11044969
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Certican® (Everolimus) Against Cytomegalovirus Disease in Renal Transplant Patients
- ClinicalTrials.gov ID
- NCT00828503
- Acronym / sponsor ID
- Certi-CMV / EudraCT: 2008-004745-28
- Conditions
- Cytomegalovirus Disease
- Keywords
- Certi-CMV, immunosuppressive switch (to Certican), renal transplant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Marcus SaemannUniversity, hospital or other
- Study start
- Dec 2008
- Primary completion
- Dec 2013 (estimated)
- Study completion
- Jun 2014 (estimated)
- First posted
- 26 Jan 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 Certican + Valganciclovir | Active comparator | Drug: Certican (everolimus) + valganciclovirValganciclovir will be administered and Certican (everolimus) will be added as immunosuppression |
| 2 Valganciclovir alone | Active comparator | Drug: ValganciclovirValganciclovir will be added alone. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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):
- no other cause of symptoms/signs identified
- informed consent of the patient
Key exclusion criteria (15 listed)
- 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)
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 |
|---|---|---|
| Certican (everolimus) + valganciclovirOral 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 | 1 Certican + Valganciclovir |
| ValganciclovirValganciclovir (or ganciclovir) will be administered alone (valganciclovir: 450 mg twice daily, ganciclovir 5 mg/kg i.v. twice daily) | Drug | 2 Valganciclovir alone |
Primary outcome
relative changes in CMV-load (copies/mL), as determined by qCMV-PCR from whole blood throughout the observational period
Time frame: 2 years
1 secondary outcome
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2012.
- Background: PubMed 16426310Humar 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.
- Background: PubMed 2254635Benichou 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.
- Background: PubMed 11044969Kasiske 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.
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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.
Sabine Schmaldienst, MD study chair
Medical University of Vienna
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Certican (everolimus) + valganciclovir and Valganciclovir in people with Cytomegalovirus Disease, run by Marcus Saemann at 1 site in Austria.
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 15 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: status not confirmed, as of the sponsor's last update on 3 Sep 2012. 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 Austria. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Marcus D Säemann, MD (+431404005593, marcus.saemann@meduniwien.ac.at), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
relative changes in CMV-load (copies/mL), as determined by qCMV-PCR from whole blood throughout the observational period (time frame: 2 years). 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 NCT00828503, which also lists 3 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 3 Sep 2012; AzTrials last refreshed its copy on 8 Nov 2026.