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

Sponsor
Instituto de Assistencia Medica ao Servidor Publico Estadual, Sao Paulo (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05354778
Collaborator
Instituto do Cancer do Estado de São Paulo (Other), Hospital Samaritano Paulista (Other), Hospital de Câncer de Barretos (Other), Fundação Faculdade Regional de Medicina de São José do Rio Preto (Other), University of Sao Paulo (Other)
180
1
2
20
9

Study Details

Study Description

Brief 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, double-blind, controlled 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.

Condition or Disease Intervention/Treatment Phase
N/A

Detailed 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, double-blind, 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, double-blind, controlled 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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
180 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
This will be a multicenter, randomized, double-blind clinical trial with two parallel groups: hydrocortisone and placebo. Data will be analyzed as "intention-to-treat".This will be a multicenter, randomized, double-blind clinical trial with two parallel groups: hydrocortisone and placebo. Data will be analyzed as "intention-to-treat".
Masking:
Double (Participant, Care Provider)
Masking Description:
Only designated pharmaceuticals will have access to randomization code. Being a soluble powder, 100mg of hydrocortisone will be diluted in a 100mL normal saline bag. The placebo will be 100mL of normal saline in the same type of bag. Both the intervention bag and the placebo bag will be covered with a black bag before being infused into the patients. Blinding will only be broken at the end of the study or in emergency situations.
Primary Purpose:
Treatment
Official Title:
HYDROcortisone Versus Placebo for Severe HospItal-acquired Pneumonia in Intensive Care Patients: the HYDRO-SHIP Study
Anticipated Study Start Date :
Jul 1, 2022
Anticipated Primary Completion Date :
Nov 1, 2023
Anticipated Study Completion Date :
Mar 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Placebo

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

Drug: Placebo
Normal saline only
Other Names:
  • NS
  • Active Comparator: Hydrocortisone

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

    Drug: Hydrocortisone
    Corticosteroid
    Other Names:
  • Solu-CORTEF
  • Outcome Measures

    Primary Outcome Measures

    1. Early Clinical Failure [Between days 3 and 7]

      Composite outcome: Death OR Respiratory worsening OR Cardiovascular worsening

    Secondary Outcome Measures

    1. Survival [Days 7 and 28]

      In the intensive care unit and in the hospital

    2. Respiratory failure [7 days]

      Need for mechanical ventilation

    3. Septic shock [7 days]

      Need for vasoactive drugs

    4. Time of mechanical ventilation [7 days]

      Number of days patients require invasive ventilation support

    5. Ventilator parameters [7 days]

      Positive end expiratory pressure (PEEP)

    6. Ventilator parameters [7 days]

      Inspired oxygen fraction (FiO2)

    7. Arterial blood gas analysis [7 days]

      Partial pressure of oxygen (PaO2)

    8. Respiratory condition [7 days]

      Horowitz index for lung function (P/F ratio) - obtained from PaO2/FiO2

    9. Time of vasoactive drugs use [7 days]

      Dosage and types of vasoactive drugs

    10. Length of stay [28 days]

      In the Intensive Care Unit and in the hospital

    11. Need for renal substitution therapy [7 days]

      Need for dialysis

    12. Radiological worsening [7 days]

      Progression of image in the chest X-ray image

    13. Adverse effects [7 days]

      psychosis, insomnia, hyperglycemia, hypernatremia, rhabdomyolysis, gastrointestinal bleeding and critical myopathy illness

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Hospital do Servidor Publico Estadual Sao Paulo Sao Paulo SP Brazil 04039-901

    Sponsors and Collaborators

    • Instituto de Assistencia Medica ao Servidor Publico Estadual, Sao Paulo
    • Instituto do Cancer do Estado de São Paulo
    • Hospital Samaritano Paulista
    • Hospital de Câncer de Barretos
    • Fundação Faculdade Regional de Medicina de São José do Rio Preto
    • University of Sao Paulo

    Investigators

    • Principal Investigator: João Manoel Silva Junior, MD, Instituto de Assistencia Medica ao Servidor Publico Estadual, Sao Paulo

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    João manoel Silva Junior, Principal Investigator, Instituto de Assistencia Medica ao Servidor Publico Estadual, Sao Paulo
    ClinicalTrials.gov Identifier:
    NCT05354778
    Other Study ID Numbers:
    • 54214821.0.1001.0068
    First Posted:
    Apr 29, 2022
    Last Update Posted:
    Apr 29, 2022
    Last Verified:
    Apr 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by João manoel Silva Junior, Principal Investigator, Instituto de Assistencia Medica ao Servidor Publico Estadual, Sao Paulo
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Apr 29, 2022