Effect of Albumin Administration in Hypoalbuminemic Hospitalized Patients With Community-acquired Pneumonia.

Study Overview
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Brief Summary
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Community-acquired pneumonia (CAP) remains a leading cause of death world-wide. Hypoalbuminemia is associated with worse outcomes. However, whether albumin administration would have a beneficial effect in outcome in patients with CAP remains uncertain. This project proposes to test the hypothesis of whether the administration of albumin in hypoalbuminemic patients with CAP would increase the proportion of clinical stable patients at day 5.

Detailed Description
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This project will consist of a superiority, non-blinded, multicentre, randomized, phase 3, interventional controlled clinical trial. The estimated sample size is of 360 patients, who will be recruited from three Spanish hospitals. Hypoalbuminemic (≤30g/L) adult patients with CAP will be randomly assigned (1:1) to receive standard care plus albumin (20g in 100ml) every 12 hours for 4 days or standard care alone. The primary endpoint will be the proportion of clinical stable patients at day 5, defined as stable vital signs for at least 24h, analyzed by intention to treat. The secondary endpoints will be time to clinical stability; duration of intravenous and total antibiotic treatment; length of hospital stay; intensive care unit admission; duration of mechanical ventilation and vasopressor treatment; adverse events; readmission within 30 days and all-cause mortality.

Official Title
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Effect of Albumin Administration on Outcomes in Hypoalbuminemic Patients Hospitalized With Community-acquired Pneumonia (ALBUCAP): a Prospective, Randomized, Phase III Clinical Controlled Trial.

Conditions
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Community-acquired Pneumonia, Hypoalbuminemia

Intervention / Treatment
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* Drug: Albumin Human


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years. Diagnosis of CAP (Chest radiography consistent with CAP AND the presence of ≥2 following prespecified clinical criteria: Fever or hypothermia; Cough; Purulent sputum; High white blood cell count; Dyspnea; Pleuritic chest pain; Signs consistent with pneumonia on chest auscultation) Serum albumin concentration ≤ 30 g/L at presentation Exclusion Criteria: Pregnancy or lactation Immunosuppression (e.g. chemotherapy or radiotherapy within 90 days, immunosuppressive drugs, corticosteroids at a minimum dose of 15mg/day of prednisone within 2 weeks of enrolment, HIV with a CD4 count below 200, solid organ transplant recipients, hematopoietic cell transplant recipients). Severe clinical status with expected survival of less than 24h. Congestive heart failure (New York Heart Association classes 3 or 4) Any contraindication for albumin administration such as hypersensitivity to albumin. Clinical conditions in which there is another indication for albumin administration (e.g. hepatic cirrhosis with ascites, malabsorption syndrome and nephrotic syndrome). Absence or impossibility of obtaining informed consent from the patient/next of kin. Patient already included in another clinical trial testing a treatment method.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A superiority, non-blinded, multicentre, randomized, interventional controlled clinical trial. Patients will be randomly assigned (1:1) to receive standard of care plus albumin (20g in 100ml) every 12 hours for 4 days or standard of care alone.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Standard care plus albumin<br>Patients will receive human albumin 20%, 20g in 100ml (Albutein Instituto Grifols, S.A. Can Guasch 2, Parets del Vallès, 08015 Barcelona, Spain) intravenously every 12 hours for 4 days or until death, discharge or clinical stability if occurring before. Patients will receive empirical antibiotic therapy according to guidelines as soon as CAP is confirmed. All microbiological assessments and additional treatment (e.g. oxygen, bronchodilators, corticosteroids, analgesic drugs, vasoactive agents, fluid resuscitation, and mechanical ventilation) will be at the discretion of the treating physicians (not the study investigators). The time of discharge and duration of antibiotics will not be determined by the study investigators, but by the treating physician team. | Drug: Albumin Human<br>* Administration of albumin 20%, 20g in 100ml (Albutein Instituto Grifols, S.A. Can Guasch 2, Parets del Vallès, 08015 Barcelona, Spain) intravenously every 12 hours for 4 days or until death, discharge or clinical stability if occurring before.<br>* Other names: Albutein;|
| No Intervention: Standard care alone<br>Patients will receive empirical antibiotic therapy according to guidelines as soon as CAP is confirmed. All microbiological assessments and additional treatment (e.g. oxygen, bronchodilators, corticosteroids, analgesic drugs, vasoactive agents, fluid resuscitation, and mechanical ventilation) will be at the discretion of the treating physicians (not the study investigators). The time of discharge and duration of antibiotics will not be determined by the study investigators, but by the treating physician team. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of clinical stable patients at day 5, measured from hospital admission. | Clinical stability will be defined as achieving normal oral intake, normal mental status (or usual level of functioning) and stable vital signs for at least 24 h, as previously described by Halm et al 1998 | Day 5±1 of hospitalization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to clinical stability (days) measured from hospital admission | The time (days) to clinical stability, measured from hospital admission | Up to 30 ±5 days after discharge | 
| Duration of intravenous and total antibiotic treatment (days). | The duration of intravenous and total duration of antibiotic treatment (measured in days) | Up to 30 ±5 days after discharge | 
| Length of hospital stay (days). | The total length of hospital stay (measured in days) | Up to hospital discharge - a median of 10 days | 
| Proportion of patients with intensive care unit (ICU) admission. | The number of patients admitted to intensive care. For those admitted to ICU we will record: time to discharge from ICU; duration of vasopressor treatment; duration of mechanical ventilation | Up to hospital discharge - a median of 10 days | 
| The rate of nosocomial infection during hospitalization | The proportion of patients with nosocomial infection during hospitalization will be registered, the type of nosocomial infection will be described | Up to hospital discharge - a median of 10 days | 
| Proportion of adverse events. | Any adverse event, its severity and its possible relationship to the study drug will be assessed | Up to 30 ±5 days after discharge | 
| The number of patients with hospital readmission within 30 days of discharge | We will document hospital readmission within 30 days of discharge | Up to 30 ±5 days after discharge | 
| All-cause mortality | 5-day mortality, 30-day mortality and mortality within 30 days of hospital discharge. | Up to 30 ±5 days after discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Community-acquired Pneumonia, Albumin, Inflammation