CMV DNAemia Pre-engraftmentNCT03889028
Pre-engraftment Cytomegalovirus DNAemia
An observational study of CMV DNAemia Pre-engraftment, run by Fundación para la Investigación del Hospital Clínico de Valencia at 1 site in Spain.
Trial summary
Cytomegalovirus (CMV) DNAemia occurs frequently in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients.Both high-level and persistent virus DNAemia are known risk factors for CMV end-organ disease and perhaps non-relapse mortality. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- CMV DNAemia Pre-engraftment
- How many people
- 878 participants
- Where
- 1 siteSpain
- Study dates
- 2 Sep 2019to 1 Sep 2020
- Phase
- Observational
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: All consecutive allo-HSCT recipients at risk of CMV infection allografted from 1st January 2010 until 31th December 2017 in Spanish transplant centers
Who may be able to join
- Recipients >18 years old
- CMV seropositive recipients and/or donors
- First allo-HSCT (T cell replete)
- CMV DNA load monitoring by real-time PCR
Who cannot join
- Recipients < 18 years
- CMV seronegative donors and recipients.
- No CMV DNA load monitoring
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pre-engraftment Cytomegalovirus DNAemia in Allogeneic Hematopoietic Stem Cell Transplant Recipients: Incidence, Risk Factors and Clinical Outcomes
Cytomegalovirus (CMV) DNAemia occurs frequently in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients.Both high-level and persistent virus DNAemia are known risk factors for CMV end-organ disease and perhaps non-relapse mortality. CMV DNAemia is usually documented after engraftment, but it may occur before. The virological features and clinical consequences of these latter early-onset episodes remain largely unexplored. The U.S. Food and Drug Administration (FDA) has recently approved letermovir for prophylaxis of CMV infection and disease in adult CMV-seropositive allo-HSCT recipients (PREVYMIS™, Merck \& Co., New Jersey, USA). In accordance with the design of the phase III, double-blind trial the drug may be administered as early as the day of transplant and no later than 28 days post-transplant. Nevertheless, the timing of drug inception should be contingent on the clinical impact of very early episodes of CMV DNAemia. In a recent work from our group (single-center study) we found that a total 38 out of the 197 patients in our series developed CMV DNAemia before engraftment (cumulative incidence (CI), 19%; 95% CI, 10-30.3%). Nine episodes of CMV DNAemia were detected prior to the time of donor progenitor cell infusion. A greater number of post-engraftment episodes required preemptive antiviral therapy compared with pre-engraftment episodes (62.5% vs 44.7%; P=0.05). The cellular content of the donor progenitor cell infusion and transplant characteristics of patients did not differ between patients with pre- or post-engraftment CMV DNAemia. The cumulative incidence of overall mortality by days 100 and 365, aGvHD by day 100 and relapse by day 365 were not significantly different between patients with pre-engraftment or post-engraftment CMV DNAemia. Our study was limited by the retrospective and single-center design and the scarce number of pre-engraftment CMV DNAemia episodes included; therefore, the results may not be extrapolated to other transplantation centers or patient cohorts. Further retrospective and prospective studies are thus required to validate the data presented herein.
Read the detailed description
Episodes of CMV DNAemia developing prior to engraftment (pre-CMV DNAemia), which usually occur between the third and fourth week after allo-HSCT, may conceivably have a different course from episodes emerging after engraftment once patients have begun to expand donor-derived T cells (post-CMV DNAemia). Thus, whether the precise timing of Letermovir treatment initiation should matter will ultimately depend on the impact of CMV DNAemia episodes developing prior to engraftment on clinical outcomes. There is limited information available on this topic. Here, we conducted a retrospective multicenter, non-interventional study to further address this issue.
- Conditions
- CMV DNAemia Pre-engraftment
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Engraftment (Days) Stratified by CMV DNaemia Occurring Before or After Neutrophil's Engraftment
absolute neutrophil count ≥500/mm3 on 3 consecutive days,, the first of which being time of engraftment.
Measured: 30 days
Secondary outcomes (2)
Overall Mortality
total number of deaths from any cause
Measured: 1 year
Non-relapse Mortality
total number of deaths without relapse or underlying disease progression
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2019
- Study start2 Sep 2019
- Primary completion1 Sep 2020
- Study completion1 Sep 2020
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.
- Other trials for CMV DNAemia Pre-engraftmentStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 878 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundación para la Investigación del Hospital Clínico de Valencia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David Navarro, Fundación para la Investigación del Hospital Clínico de Valencia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03889028
- Sponsor's protocol ID
- NAV-CMV-2019
- Status last verified
- Nov 2020
- First submitted
- 22 Mar 2019
- Last updated
- 11 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pre-engraftment Cytomegalovirus DNAemia in Allogeneic Hematopoietic Stem Cell Transplant Recipients: Incidence, Risk Factors and Clinical Outcomes
- ClinicalTrials.gov ID
- NCT03889028
- Acronym / sponsor ID
- NAV-CMV-2019
- Conditions
- CMV DNAemia Pre-engraftment
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 878 participants (actual)
- Lead sponsor
- Fundación para la Investigación del Hospital Clínico de ValenciaUniversity, hospital or other
- Study start
- 2 Sep 2019 (actual)
- Primary completion
- 1 Sep 2020 (actual)
- Study completion
- 1 Sep 2020 (actual)
- First posted
- 25 Mar 2019 (actual)
- Results
- Posted 11 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cytomegalovirus (CMV) DNAemia occurs frequently in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients.Both high-level and persistent virus DNAemia are known risk factors for CMV end-organ disease and perhaps non-relapse mortality. CMV DNAemia is usually documented after engraftment, but it may occur before. The virological features and clinical consequences of these latter early-onset episodes remain largely unexplored. The U.S. Food and Drug Administration (FDA) has recently approved letermovir for prophylaxis of CMV infection and disease in adult CMV-seropositive allo-HSCT recipients (PREVYMIS™, Merck \& Co., New Jersey, USA). In accordance with the design of the phase III, double-blind trial the drug may be administered as early as the day of transplant and no later than 28 days post-transplant. Nevertheless, the timing of drug inception should be contingent on the clinical impact of very early episodes of CMV DNAemia. In a recent work from our group (single-center study) we found that a total 38 out of the 197 patients in our series developed CMV DNAemia before engraftment (cumulative incidence (CI), 19%; 95% CI, 10-30.3%). Nine episodes of CMV DNAemia were detected prior to the time of donor progenitor cell infusion. A greater number of post-engraftment episodes required preemptive antiviral therapy compared with pre-engraftment episodes (62.5% vs 44.7%; P=0.05). The cellular content of the donor progenitor cell infusion and transplant characteristics of patients did not differ between patients with pre- or post-engraftment CMV DNAemia. The cumulative incidence of overall mortality by days 100 and 365, aGvHD by day 100 and relapse by day 365 were not significantly different between patients with pre-engraftment or post-engraftment CMV DNAemia. Our study was limited by the retrospective and single-center design and the scarce number of pre-engraftment CMV DNAemia episodes included; therefore, the results may not be extrapolated to other transplantation centers or patient cohorts. Further retrospective and prospective studies are thus required to validate the data presented herein.
Detailed description
Episodes of CMV DNAemia developing prior to engraftment (pre-CMV DNAemia), which usually occur between the third and fourth week after allo-HSCT, may conceivably have a different course from episodes emerging after engraftment once patients have begun to expand donor-derived T cells (post-CMV DNAemia). Thus, whether the precise timing of Letermovir treatment initiation should matter will ultimately depend on the impact of CMV DNAemia episodes developing prior to engraftment on clinical outcomes. There is limited information available on this topic. Here, we conducted a retrospective multicenter, non-interventional study to further address this issue.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All consecutive allo-HSCT recipients at risk of CMV infection allografted from 1st January 2010 until 31th December 2017 in Spanish transplant centers
Key inclusion criteria (4 listed)
- Recipients >18 years old
- CMV seropositive recipients and/or donors
- First allo-HSCT (T cell replete)
- CMV DNA load monitoring by real-time PCR
Key exclusion criteria (3 listed)
- Recipients < 18 years
- CMV seronegative donors and recipients.
- No CMV DNA load monitoring
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Time to Engraftment (Days) Stratified by CMV DNaemia Occurring Before or After Neutrophil's Engraftment
Time frame: 30 days
absolute neutrophil count ≥500/mm3 on 3 consecutive days,, the first of which being time of engraftment.
2 secondary outcomes
Overall Mortality
Time frame: 1 year
Non-relapse Mortality
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of CMV DNAemia Pre-engraftment, run by Fundación para la Investigación del Hospital Clínico de Valencia at 1 site in Spain.
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 3 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 11 Dec 2020. 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 Spain. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Dec 2020). 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?
Time to Engraftment (Days) Stratified by CMV DNaemia Occurring Before or After Neutrophil's Engraftment (time frame: 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Dec 2020.