HYDROcortisone Versus Placebo for Severe HospItal-acquired Pneumonia in Intensive Care Patients: the HYDRO-SHIP Study

Обзор

The use of corticosteroids in patients with severe community pneumonia, bacterial infection which kills lots of patients around the world, reduces the mortality of this infection. However, there are no studies with this type of drug regarding hospital-acquired pneumonia. This is the first multicenter randomized trial to test hydrocortisone plus standard therapy in critical care patients with nosocomial pneumonia. This intervention is inexpensive and may improve the outcome of those patients, besides having an acceptable side effects profile.

Подробное описание

Introduction and Objectives: the use of corticosteroids in patients with severe community pneumonia reduces morbimortality. However, to our knowledge, there are no studies with steroids for patients in intensive care with nosocomial pneumonia, among which those with ventilator associated pneumonia, infections which carry a high mortality rate. The treatment for those diseases involves intensive care and antibiotics, but there is a need for inexpensive, adjuvant therapies which improve the outcome for those patients. Therefore, the objective of this study is to compare hydrocortisone versus placebo, both with standard therapy, in the outcome of critical care patients diagnosed with nosocomial pneumonia. Methods: multicenter randomized, open-label, controlled trial, with two parallel groups: hydrocortisone or placebo, associated with nosocomial pneumonia's standard treatment. Patients with viral or other etiologies of pneumonia are excluded, as well as corticosteroids chronical users, or patients with conditions which demand this type of therapy. Intravenous 100mg of hydrocortisone and normal saline (the placebo) are tested every eight hours for five days or until intensive care unit (ICU) discharge or until the patient dies. The sample is 180 patients, 90 in each group, in different ICUs in Brazil. The primary outcome is early clinical failure. The secondary outcomes are survival and mortality in both groups, need for intubation, mechanical ventilation, vasoactive drugs and dialysis, lengths of stay in the hospital and in the ICU, radiological progression and adverse events. Discussion, risks, and benefits: this is the first multicenter randomized trial to test hydrocortisone plus standard therapy in critical care patients with nosocomial pneumonia. This intervention is inexpensive and may improve the outcome of those patients, besides having an acceptable side effects profile. Weighing the benefits and risks of this study, as well as its strengths and potential weaknesses, it is believed that its realization is justified, in addition to bringing important advances in the field of intensive care.

Вмешательства

• Препарат Hydrocortisone
  Corticosteroid
• Препарат Placebo
  Normal saline only

Первичные конечные точки

• Early Clinical Failure [Срок оценки: Between days 0 and 7 for death; between days 3 and 7 for respiratory or cardiovascular worsening]

Вторичные конечные точки (12)

• Survival [Срок оценки: Days 7 and 28]
• Respiratory failure [Срок оценки: 7 days]
• Septic shock [Срок оценки: 7 days]
• Time of mechanical ventilation [Срок оценки: 7 days]
• Ventilator parameters (1) [Срок оценки: 7 days]
• Ventilator parameters (2) [Срок оценки: 7 days]
• Arterial blood gas analysis [Срок оценки: 7 days]
• Respiratory condition [Срок оценки: 7 days]
• Time of vasoactive drugs use [Срок оценки: 7 days]
• Length of stay [Срок оценки: 28 days]
• Need for renal substitution therapy [Срок оценки: 7 days]
• Radiological worsening [Срок оценки: 7 days]

Критерии участия

Критерии включения

• 18 years of age or older
• Suspected ou confirmed case of bacterial nosocomial pneumonia (including ventilator-associated pneumonia)
• Intensive Care Unit stay
• Signed consent form (by the patient or a legal guardian)

Критерии исключения

• Women who are pregnant, have recently given birth or are breastfeeding
• Patients who are moribund or do not have a treatment perspective
• Patients with community acquired pneumonia
• Patients with other types of pneumonia (viral - including COVID-19, fungal etc.)
• Those with pulmonary infiltrates in chest image which are not compatible with bacterial pneumonia
• Patients with adrenal insufficiency
• Patients who have a condition that demands the use of corticosteroids (acute or chronic)
• Patients allergic to hydrocortisone
• Patients with refractory septic shock (those receiving more than 0,5mcg/kg/min of norepinephrine)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Бразилия · 1 центр

• Hospital do Servidor Publico Estadual — São Paulo

Публикации

• Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287. PMID 26903338
• Annane D, Sebille V, Charpentier C, Bollaert PE, Francois B, Korach JM, Capellier G, Cohen Y, Azoulay E, Troche G, Chaumet-Riffaud P, Bellissant E. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002 Aug 21;288(7):862-71. doi: 10.1001/jama.288.7.862. PMID 12186604
• Sprung CL, Annane D, Keh D, Moreno R, Singer M, Freivogel K, Weiss YG, Benbenishty J, Kalenka A, Forst H, Laterre PF, Reinhart K, Cuthbertson BH, Payen D, Briegel J; CORTICUS Study Group. Hydrocortisone therapy for patients with septic shock. N Engl J Med. 2008 Jan 10;358(2):111-24. doi: 10.1056/NEJMoa071366. PMID 18184957
• Annane D, Renault A, Brun-Buisson C, Megarbane B, Quenot JP, Siami S, Cariou A, Forceville X, Schwebel C, Martin C, Timsit JF, Misset B, Ali Benali M, Colin G, Souweine B, Asehnoune K, Mercier E, Chimot L, Charpentier C, Francois B, Boulain T, Petitpas F, Constantin JM, Dhonneur G, Baudin F, Combes A, Bohe J, Loriferne JF, Amathieu R, Cook F, Slama M, Leroy O, Capellier G, Dargent A, Hissem T, Max PMID 29490185
• Annane D, Pastores SM, Rochwerg B, Arlt W, Balk RA, Beishuizen A, Briegel J, Carcillo J, Christ-Crain M, Cooper MS, Marik PE, Umberto Meduri G, Olsen KM, Rodgers SC, Russell JA, Van den Berghe G. Guidelines for the Diagnosis and Management of Critical Illness-Related Corticosteroid Insufficiency (CIRCI) in Critically Ill Patients (Part I): Society of Critical Care Medicine (SCCM) and European Soci PMID 28938253
• RECOVERY Collaborative Group; Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, Staplin N, Brightling C, Ustianowski A, Elmahi E, Prudon B, Green C, Felton T, Chadwick D, Rege K, Fegan C, Chappell LC, Faust SN, Jaki T, Jeffery K, Montgomery A, Rowan K, Juszczak E, Baillie JK, Haynes R, Landray MJ. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693- PMID 32678530
• WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group; Sterne JAC, Murthy S, Diaz JV, Slutsky AS, Villar J, Angus DC, Annane D, Azevedo LCP, Berwanger O, Cavalcanti AB, Dequin PF, Du B, Emberson J, Fisher D, Giraudeau B, Gordon AC, Granholm A, Green C, Haynes R, Heming N, Higgins JPT, Horby P, Juni P, Landray MJ, Le Gouge A, Leclerc M, Lim WS, Machado FR, McArthur C, Meziani F, PMID 32876694
• Stern A, Skalsky K, Avni T, Carrara E, Leibovici L, Paul M. Corticosteroids for pneumonia. Cochrane Database Syst Rev. 2017 Dec 13;12(12):CD007720. doi: 10.1002/14651858.CD007720.pub3. PMID 29236286

Идентификаторы

NCT: NCT05354778 · 54214821.0.1001.0068

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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