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

Instituto de Assistencia Medica ao Servidor Publico Estadual, Sao Paulo

Status: Enrolling

Conditions: Ventilator Associated Pneumonia; Healthcare-Associated Pneumonia

Treatments: Drug: Placebo; Drug: Hydrocortisone

Study type: Interventional

Funder types: Other

Identifiers

NCT05354778

54214821.0.1001.0068

Details and patient eligibility

About

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.

Full 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.

Enrollment: 180 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

180 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Normal saline 100mL every 8 hours for 5 days or until patient dies or is discharged from the intensive care unit

Treatment:

Drug: Placebo

Hydrocortisone

Active Comparator group

Description:

Hydrocortisone 100mg + normal saline 100mL every 8 hours for 5 days or until patient dies or is discharged from the intensive care unit

Treatment:

Drug: Hydrocortisone