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Cytomegalovirus Infection in Critically Ill Patients and Patients Receiving Anticancer Therapy (CMV-ICU)

20 de fevereiro de 2020 atualizado por: Fundación de investigación HM

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).

Visão geral do estudo

Status

Desconhecido

Condições

Intervenção / Tratamento

Descrição detalhada

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:

  1. Which is the incidence of CMV infection and disease?
  2. What is the natural evolution of CMV infections that do not receive anti-CMV treatment?
  3. What is the impact of anti-CMV treatment in the patient´s outcome (mortality, days under mechanical ventilation and days at ICU)?
  4. What are the risk and protective factors for developing CMV infection after ICU admission?

Tipo de estudo

Observacional

Inscrição (Antecipado)

400

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

18 anos e mais velhos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Sim

Gêneros Elegíveis para o Estudo

Tudo

Método de amostragem

Amostra Não Probabilística

População do estudo

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.

Descrição

Inclusion Criteria:

  1. age >=18 y.o.,
  2. admission to the intensive care unit with an expectancy to stay longer than 72 hours and requiring invasive mechanical ventilation.

Exclusion Criteria:

  1. survival expectation previous to ICU admission less than 6 months,
  2. intubation after 12 hours of ICU admission
  3. limitation of the therapeutic effort previous or during the ICU stay,
  4. admission to the ICU during the previous 3 months
  5. not agreeing to sign an informed consent.

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

Coortes e Intervenções

Grupo / Coorte
Intervenção / Tratamento
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.

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.
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.

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.

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Cytomegalovirus Prevalence
Prazo: 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
From study start date (March, 2020) until ending enrollment period (16 months later)

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Antecipado)

1 de março de 2020

Conclusão Primária (Antecipado)

31 de dezembro de 2021

Conclusão do estudo (Antecipado)

31 de dezembro de 2022

Datas de inscrição no estudo

Enviado pela primeira vez

17 de fevereiro de 2020

Enviado pela primeira vez que atendeu aos critérios de CQ

20 de fevereiro de 2020

Primeira postagem (Real)

21 de fevereiro de 2020

Atualizações de registro de estudo

Última Atualização Postada (Real)

21 de fevereiro de 2020

Última atualização enviada que atendeu aos critérios de controle de qualidade

20 de fevereiro de 2020

Última verificação

1 de fevereiro de 2020

Mais Informações

Termos relacionados a este estudo

Outros números de identificação do estudo

  • 19.09.1441-GHM
  • HM-CMV19 (Número de outro subsídio/financiamento: MSD)

Plano para dados de participantes individuais (IPD)

Planeja compartilhar dados de participantes individuais (IPD)?

NÃO

Descrição do plano IPD

Scientific congress and JCR publications

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Não

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

Ensaios clínicos em CMV

Ensaios clínicos em Real time PCR

3
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