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

Ventilator Associated Pneumonia Clinical Trial

— HYDRO-SHIP  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05354778
• Other study ID #: 54214821.0.1001.0068
• Status: Recruiting
• Phase: N/A
• Start date: October 16, 2022
• Est. completion date: July 2024

Study information

• Verified date: January 2024
• Source: Instituto de Assistencia Medica ao Servidor Publico Estadual, Sao Paulo
• Contact: Dante Raglione, MD
• Phone: 5511984471792
• Email: danraglione[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 will be 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.

Description:

Introduction and Objectives: the use of corticosteroids in patients with severe community pneumonia, bacterial infection which kills lots of patients around the world, 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 will be 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) will be tested every eight hours for five days or until intensive care unit (ICU) discharge or until the patient dies. The sample will be of 180 patients, 90 in each group, in different ICUs in Brazil. The primary outcome will be early clinical failure between the third and seventh days of the patient's inclusion in the study. The secondary outcomes will be 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 and radiological progression. Moreover, we will analyze adverse events and there will be a safety interim analysis when 25% of the whole sample is recruited, which may interrupt the study in case of a high frequency of such events (> 15% grade 3 or 4 as defined by the FDA). Finally, we will conduct an efficacy interim analysis when 50% of the sample is recruited. The study will be interrupted only if there is a statistical significant difference regarding the primary outcome with p < 0.001 (Haybittle-Peto criteria). Discussion, risks, and benefits: this will be 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: July 2024
• Est. primary completion date: April 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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)

Exclusion Criteria:

• 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)

Related Conditions & MeSH terms

• Healthcare-Associated Pneumonia
• Pneumonia
• Pneumonia, Ventilator-Associated
• Ventilator Associated Pneumonia

Intervention

Drug:
• Hydrocortisone
Corticosteroid
• Placebo
Normal saline only

Locations

Country	Name	City	State
Brazil	Hospital do Servidor Publico Estadual	Sao Paulo	Sao Paulo SP

Sponsors (4)

Lead Sponsor	Collaborator
Instituto de Assistencia Medica ao Servidor Publico Estadual, Sao Paulo	Hospital de Câncer de Barretos, Instituto do Cancer do Estado de São Paulo, University of Sao Paulo

Country where clinical trial is conducted

Brazil, 

References & Publications (21)

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* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Early Clinical Failure	Composite outcome: Death OR Respiratory worsening OR Cardiovascular worsening	Between days 3 and 7
Secondary	Survival	In the intensive care unit and in the hospital	Days 7 and 28
Secondary	Respiratory failure	Need for mechanical ventilation	7 days
Secondary	Septic shock	Need for vasoactive drugs	7 days
Secondary	Time of mechanical ventilation	Number of days patients require invasive ventilation support	7 days
Secondary	Ventilator parameters	Positive end expiratory pressure (PEEP)	7 days
Secondary	Ventilator parameters	Inspired oxygen fraction (FiO2)	7 days
Secondary	Arterial blood gas analysis	Partial pressure of oxygen (PaO2)	7 days
Secondary	Respiratory condition	Horowitz index for lung function (P/F ratio) - obtained from PaO2/FiO2	7 days
Secondary	Time of vasoactive drugs use	Dosage and types of vasoactive drugs	7 days
Secondary	Length of stay	In the Intensive Care Unit and in the hospital	28 days
Secondary	Need for renal substitution therapy	Need for dialysis	7 days
Secondary	Radiological worsening	Progression of image in the chest X-ray image	7 days
Secondary	Adverse effects	psychosis, insomnia, hyperglycemia, hypernatremia, rhabdomyolysis, gastrointestinal bleeding and critical myopathy illness	7 days