CMVCMV-ICUNCT04280380
Cytomegalovirus Infection in Critically Ill Patients and Patients Receiving Anticancer Therapy
An observational study of CMV, run by Fundación de investigación HM.
Trial summary
Cytomegalovirus (CMV) is the most common member of the herpes viruses to infect humans. Its double-stranded linear DNA duplex contains 165 genes that encode viral proteins that mimic and interact with human cellular proteins and are related to its virulence and latency. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- CMV
- What is being tested?
- Real time PCR
- How many people
- 400 participants
- Where
- No sites listed yet
- Study dates
- 1 Mar 2020to 31 Dec 2022
- Phase
- Observational
- 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
- Healthy volunteers accepted
- Adult, Older adult
Study population: Individuals with >=18 years old, after admission to the intensive care unit with an expectancy to stay longer than 72 hours and requiring invasive mechanical ventilation, whom are not included at exclusion criteria.
Who may be able to join
- age >=18 y.o.,
- admission to the intensive care unit with an expectancy to stay longer than 72 hours and requiring invasive mechanical ventilation.
Who cannot join
- survival expectation previous to ICU admission less than 6 months,
- intubation after 12 hours of ICU admission
- limitation of the therapeutic effort previous or during the ICU stay,
- admission to the ICU during the previous 3 months
- not agreeing to sign an informed consent.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Incidence, Natural History and Outcome of Cytomegalovirus Infection in Critically Ill Patients and Patients Receiving Anticancer Therapy
Cytomegalovirus (CMV) is the most common member of the herpes viruses to infect humans. Its double-stranded linear DNA duplex contains 165 genes that encode viral proteins that mimic and interact with human cellular proteins and are related to its virulence and latency. CMV primary infection is usually acquired in the adolescence and follows a benign course; however it might reactivate in patients with immune suppression leading to a high mortality and morbidity in this group of patients. There is growing evidence that critically ill immunocompetent patients can develop CMV disease [Limaye et al. JAMA. 2008;300(4):413; Ziemann et al. Crit Care Med. 2008;36(12):3145]. However, results of the incidence of CMV disease in critically ill patients is unpredictable due to the wide range of these results, from a 0% to 98% [Al-Omari et al. Ann. Intensive Care (2016) 6:110]. This inconsistency could be explained by many factors such as (i) variation in the definition of CMV disease (old studies consider seropositivity as evidence of disease, while others use newer technologies like PCR and/or antigen detection), (ii) variation in inclusion criteria (some studies include only seropositive patients therefore assessing reactivation rate of CMV, others also include seronegative patients thus evaluating also new infections) or (iii) variation in studied populations (e.g. septic, surgical, burn or postcardiac surgery patients or patients under mechanical ventilation).
Read the detailed description
Evidence in the literature has demonstrated how different factors have been associated with CMV disease; however, the effect of new anticancer therapies (personalized chemotherapies, biological and immunological treatments, extreme surgery, etc.) on CMV disease is unknown. The investigators believe that studying this subgroup of patients should be one of the primary issues as the number of patients with these characteristics will increase significantly in the near future.
Likewise, it is important to point out that in the real world diagnosing CMV disease is a real challenge for the intensive care physician (due to subclinical or not specific clinical presentations, confusion factors, low clinical suspicions, etc.) thus its diagnosis and eventual treatment could be improved. These undesired diagnostic and therapeutic flaws provide a unique opportunity to (i) describe the natural evolution of the disease, (ii) address the effect of the disease in the outcome of the patients and (iii) estimate the potential number of patients that could benefit from a new management.
HM Hospitales (https://www.hmhospitales.com/) is a Spanish private group made up of five tertiary university hospitals in Madrid (HM Madrid, HM Torrelodones, HM Sanchinarro, HM Puerta del Sur y HM Monteprincipe). In addition, the group has a specialized center focused in cancer ("Clara Campal" oncologic center https://www.hmciocc.com/ ) with a phase I Unit (STAR-CIOCC http://startmadrid.com/index.php/en/2014-10-02-23-29-01/madrid-locations/2014-10-10-00-46-42), five medical-surgical ICUs (one in each hospital) that assist 1200 patients/year (35% with cancer) and a surgical department specialized in robotic and laparoscopic procedures.
To define the incidence of CMV reactivation and disease is of paramount importance as several studies have suggested an association between CMV disease and an increased mortality rate, prolonged mechanical ventilation as well as length of ICU and hospital stay. Furthermore, CMV disease increases the risk of acquiring a nosocomial infection that could also have an effect on the outcome of the patients [Ziemann et al. Crit Care Med. 2008;36(12):3145; Sinclair. J Clin Virol. 2008;41(3):180]. Likewise, as several anti-CMV treatments are (valacyclovir, valanciclovir, ganciclovir, foscarnet or cidofovir), or will be shortly (letermovir), available the increased morbidity and mortality associated to this infection in critically ill patients could be improved dramatically.
This research proposal is seeking to answer four questions in a general ICU cohort of patients and in the subgroup of critically ill patients receiving anti-cancer therapy:
- Which is the incidence of CMV infection and disease?
- What is the natural evolution of CMV infections that do not receive anti-CMV treatment?
- What is the impact of anti-CMV treatment in the patient´s outcome (mortality, days under mechanical ventilation and days at ICU)?
- What are the risk and protective factors for developing CMV infection after ICU admission?
- Conditions
- CMV
- Being tested
- Real time PCR
- Keywords
- CMV, intensive care, prevalence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Real time PCRDiagnostic test
At inclusion, serum samples will be collected to determine CMV serological status. Plasma samples will be collected weekly for CMV PCR analysis. Antibodies for CMV will be assessed using a commercial enzyme immunoassay kit for detection of total antibodies to CMV (LIAISON CMV IgG assay, DiaSorin S.p.A). DNA will be extracted in 200 μL of plasma eluted in 60 μL of elution buffer using a NucliSENS easyMAG system (bioMérieux, Boxtel, The Netherlands). Samples will be amplified using Affigene CMV Trender diagnostic assay (Cepheid AB, Bromma, Sweden), according to the manufacturer instructions. Amplification will be performed on a MX3000P instrument (Stratagene Instruments Systems, La Jolla, CA, USA). Samples with >500 copies/mL of plasma will be considered positive.
| Study group | Role | What they receive |
|---|---|---|
| Mechanical ventilated patients without cancer | This observational, cohort, retrospective and multicenter study will be performed during a period of 16 months at the 5 medical/surgical ICUs from HM Hospitals group.
The recruitment will be performed by volume of patients: recruitment of the first 300 patients without cancer will start the 15th of January 2018 and will end once the last patient has been included; likewise, recruitment of the first patient with cancer will start on the same date and will end once the last patient (of 100) is recruited. Patients undergoing any type of anticancer therapy within the previous 3 month of ICU admission will be analyzed as part of the overall group but also as an independent subgroup of patients.
Inclusion criteria: (a) age >=18 y.o., (b) admission to the intensive care unit with an expectancy to stay longer than 72 hours and requiring invasive mechanical ventilation. Receives: Diagnostic Test: Real time PCR | |
| Mechanical ventilated patients with cancer | This observational, cohort, retrospective and multicenter study will be performed during a period of 16 months at the 5 medical/surgical ICUs from HM Hospitals group.
The recruitment will be performed by volume of patients: recruitment of the first 300 patients without cancer will start the 15th of January 2018 and will end once the last patient has been included; likewise, recruitment of the first patient with cancer will start on the same date and will end once the last patient (of 100) is recruited. Patients undergoing any type of anticancer therapy within the previous 3 month of ICU admission will be analyzed as part of the overall group but also as an independent subgroup of patients.
Inclusion criteria: (a) age >=18 y.o., (b) admission to the intensive care unit with an expectancy to stay longer than 72 hours and requiring invasive mechanical ventilation. Receives: Diagnostic Test: Real time PCR |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cytomegalovirus Prevalence
Cytomegalovirus prevalence after admission to the intensive care unit with an expectancy to stay longer than 72 hours
Measured: From study start date (March, 2020) until ending enrollment period (16 months later)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2020
- Study start1 Mar 2020 (estimated)
- Primary completion31 Dec 2021 (estimated)
- Study completion31 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CMVStudies 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
- Prospective
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fundación de investigación HM
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04280380
- Sponsor's protocol ID
- 19.09.1441-GHM
- Other IDs
- HM-CMV19
- Acronym
- CMV-ICU
- Status last verified
- Feb 2020
- First submitted
- 17 Feb 2020
- Last updated
- 21 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Scientific congress and JCR publications
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Incidence, Natural History and Outcome of Cytomegalovirus Infection in Critically Ill Patients and Patients Receiving Anticancer Therapy
- ClinicalTrials.gov ID
- NCT04280380
- Acronym / sponsor ID
- CMV-ICU / 19.09.1441-GHM
- Conditions
- CMV
- Keywords
- CMV, intensive care, prevalence
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- Fundación de investigación HMUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 1 Mar 2020 (estimated)
- Primary completion
- 31 Dec 2021 (estimated)
- Study completion
- 31 Dec 2022 (estimated)
- First posted
- 21 Feb 2020 (actual)
- 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.
Cytomegalovirus (CMV) is the most common member of the herpes viruses to infect humans. Its double-stranded linear DNA duplex contains 165 genes that encode viral proteins that mimic and interact with human cellular proteins and are related to its virulence and latency. CMV primary infection is usually acquired in the adolescence and follows a benign course; however it might reactivate in patients with immune suppression leading to a high mortality and morbidity in this group of patients. There is growing evidence that critically ill immunocompetent patients can develop CMV disease [Limaye et al. JAMA. 2008;300(4):413; Ziemann et al. Crit Care Med. 2008;36(12):3145]. However, results of the incidence of CMV disease in critically ill patients is unpredictable due to the wide range of these results, from a 0% to 98% [Al-Omari et al. Ann. Intensive Care (2016) 6:110]. This inconsistency could be explained by many factors such as (i) variation in the definition of CMV disease (old studies consider seropositivity as evidence of disease, while others use newer technologies like PCR and/or antigen detection), (ii) variation in inclusion criteria (some studies include only seropositive patients therefore assessing reactivation rate of CMV, others also include seronegative patients thus evaluating also new infections) or (iii) variation in studied populations (e.g. septic, surgical, burn or postcardiac surgery patients or patients under mechanical ventilation).
Detailed description
Evidence in the literature has demonstrated how different factors have been associated with CMV disease; however, the effect of new anticancer therapies (personalized chemotherapies, biological and immunological treatments, extreme surgery, etc.) on CMV disease is unknown. The investigators believe that studying this subgroup of patients should be one of the primary issues as the number of patients with these characteristics will increase significantly in the near future.
Likewise, it is important to point out that in the real world diagnosing CMV disease is a real challenge for the intensive care physician (due to subclinical or not specific clinical presentations, confusion factors, low clinical suspicions, etc.) thus its diagnosis and eventual treatment could be improved. These undesired diagnostic and therapeutic flaws provide a unique opportunity to (i) describe the natural evolution of the disease, (ii) address the effect of the disease in the outcome of the patients and (iii) estimate the potential number of patients that could benefit from a new management.
HM Hospitales (https://www.hmhospitales.com/) is a Spanish private group made up of five tertiary university hospitals in Madrid (HM Madrid, HM Torrelodones, HM Sanchinarro, HM Puerta del Sur y HM Monteprincipe). In addition, the group has a specialized center focused in cancer ("Clara Campal" oncologic center https://www.hmciocc.com/ ) with a phase I Unit (STAR-CIOCC http://startmadrid.com/index.php/en/2014-10-02-23-29-01/madrid-locations/2014-10-10-00-46-42), five medical-surgical ICUs (one in each hospital) that assist 1200 patients/year (35% with cancer) and a surgical department specialized in robotic and laparoscopic procedures.
To define the incidence of CMV reactivation and disease is of paramount importance as several studies have suggested an association between CMV disease and an increased mortality rate, prolonged mechanical ventilation as well as length of ICU and hospital stay. Furthermore, CMV disease increases the risk of acquiring a nosocomial infection that could also have an effect on the outcome of the patients [Ziemann et al. Crit Care Med. 2008;36(12):3145; Sinclair. J Clin Virol. 2008;41(3):180]. Likewise, as several anti-CMV treatments are (valacyclovir, valanciclovir, ganciclovir, foscarnet or cidofovir), or will be shortly (letermovir), available the increased morbidity and mortality associated to this infection in critically ill patients could be improved dramatically.
This research proposal is seeking to answer four questions in a general ICU cohort of patients and in the subgroup of critically ill patients receiving anti-cancer therapy:
- Which is the incidence of CMV infection and disease?
- What is the natural evolution of CMV infections that do not receive anti-CMV treatment?
- What is the impact of anti-CMV treatment in the patient´s outcome (mortality, days under mechanical ventilation and days at ICU)?
- What are the risk and protective factors for developing CMV infection after ICU admission?
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mechanical ventilated patients without cancer | – | Diagnostic Test: Real time PCRThis observational, cohort, retrospective and multicenter study will be performed during a period of 16 months at the 5 medical/surgical ICUs from HM Hospitals group. The recruitment will be performed by volume of patients: recruitment of the first 300 patients without cancer will start the 15th of January 2018 and will end once the last patient has been included; likewise, recruitment of the first patient with cancer will start on the same date and will end once the last patient (of 100) is recruited. Patients undergoing any type of anticancer therapy within the previous 3 month of ICU admission will be analyzed as part of the overall group but also as an independent subgroup of patients. Inclusion criteria: (a) age >=18 y.o., (b) admission to the intensive care unit with an expectancy to stay longer than 72 hours and requiring invasive mechanical ventilation. |
| Mechanical ventilated patients with cancer | – | Diagnostic Test: Real time PCRThis observational, cohort, retrospective and multicenter study will be performed during a period of 16 months at the 5 medical/surgical ICUs from HM Hospitals group. The recruitment will be performed by volume of patients: recruitment of the first 300 patients without cancer will start the 15th of January 2018 and will end once the last patient has been included; likewise, recruitment of the first patient with cancer will start on the same date and will end once the last patient (of 100) is recruited. Patients undergoing any type of anticancer therapy within the previous 3 month of ICU admission will be analyzed as part of the overall group but also as an independent subgroup of patients. Inclusion criteria: (a) age >=18 y.o., (b) admission to the intensive care unit with an expectancy to stay longer than 72 hours and requiring invasive mechanical ventilation. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Individuals with >=18 years old, after admission to the intensive care unit with an expectancy to stay longer than 72 hours and requiring invasive mechanical ventilation, whom are not included at exclusion criteria.
Key inclusion criteria (2 listed)
- age >=18 y.o.,
- admission to the intensive care unit with an expectancy to stay longer than 72 hours and requiring invasive mechanical ventilation.
Key exclusion criteria (5 listed)
- survival expectation previous to ICU admission less than 6 months,
- intubation after 12 hours of ICU admission
- limitation of the therapeutic effort previous or during the ICU stay,
- admission to the ICU during the previous 3 months
- not agreeing to sign an informed consent.
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 |
|---|---|---|
| Real time PCRAt inclusion, serum samples will be collected to determine CMV serological status. Plasma samples will be collected weekly for CMV PCR analysis. Antibodies for CMV will be assessed using a commercial enzyme immunoassay kit for detection of total antibodies to CMV (LIAISON CMV IgG assay, DiaSorin S.p.A). DNA will be extracted in 200 μL of plasma eluted in 60 μL of elution buffer using a NucliSENS easyMAG system (bioMérieux, Boxtel, The Netherlands). Samples will be amplified using Affigene CMV Trender diagnostic assay (Cepheid AB, Bromma, Sweden), according to the manufacturer instructions. Amplification will be performed on a MX3000P instrument (Stratagene Instruments Systems, La Jolla, CA, USA). Samples with >500 copies/mL of plasma will be considered positive. | Diagnostic test | Mechanical ventilated patients with cancer, Mechanical ventilated patients without cancer |
Primary outcome
Cytomegalovirus Prevalence
Time frame: From study start date (March, 2020) until ending enrollment period (16 months later)
Cytomegalovirus prevalence after admission to the intensive care unit with an expectancy to stay longer than 72 hours
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2020.
- Individual participant dataSharing planned: No. Scientific congress and JCR publications
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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.
Questions about this trial
What is this clinical trial studying?
An observational study of CMV, run by Fundación de investigación HM.
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 2 inclusion and 5 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 21 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Fernando Gómez, Msc (917089900 ext. 2553, fghermoso@hmhospitales.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cytomegalovirus Prevalence (time frame: From study start date (March, 2020) until ending enrollment period (16 months later)). 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 21 Feb 2020.