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

2020年2月20日 更新者: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).

調査の概要

状態

わからない

条件

詳細な説明

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?

研究の種類

観察的

入学 (予想される)

400

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

18年歳以上 (大人、高齢者)

健康ボランティアの受け入れ

はい

受講資格のある性別

全て

サンプリング方法

非確率サンプル

調査対象母集団

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.

説明

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.

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか?

デザインの詳細

コホートと介入

グループ/コホート
介入・治療
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.

この研究は何を測定していますか?

主要な結果の測定

結果測定
メジャーの説明
時間枠
Cytomegalovirus Prevalence
時間枠: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)

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (予想される)

2020年3月1日

一次修了 (予想される)

2021年12月31日

研究の完了 (予想される)

2022年12月31日

試験登録日

最初に提出

2020年2月17日

QC基準を満たした最初の提出物

2020年2月20日

最初の投稿 (実際)

2020年2月21日

学習記録の更新

投稿された最後の更新 (実際)

2020年2月21日

QC基準を満たした最後の更新が送信されました

2020年2月20日

最終確認日

2020年2月1日

詳しくは

本研究に関する用語

キーワード

その他の研究ID番号

  • 19.09.1441-GHM
  • HM-CMV19 (その他の助成金/資金番号:MSD)

個々の参加者データ (IPD) の計画

個々の参加者データ (IPD) を共有する予定はありますか?

いいえ

IPD プランの説明

Scientific congress and JCR publications

医薬品およびデバイス情報、研究文書

米国FDA規制医薬品の研究

いいえ

米国FDA規制機器製品の研究

いいえ

この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。

CMVの臨床試験

Real time PCRの臨床試験

3
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