Clinical Research Directory

Amoxicillin Alone Versus Amoxicillin/Clavulanate for Community-acquired Pneumonia in Patients Aged 65 Years or Older, and Hospitalized in a Non-intensive Care Unit Ward

Reduce inappropriate antibiotic use is a priority of public health agencies. Community-acquired pneumonia (CAP) is one of the most important indications for antibiotic prescriptions. In the majority of the studies of CAP, there is a large proportion of cases with no pathogen identified. Thus, the choice of the empirical antibiotic depends on the most likely pathogen, individual risk factors, comorbidities, and allergies. Patients aged 65 years or older are often treated with amoxicillin/clavulanate or with another broad-spectrum antibiotic (third-generation cephalosporins, antipneumococcal fluoroquinolone). However, broad-spectrum antibiotic prescription in CAP is debated and concerns exist about side-effects and selective pressure for resistance. Due to lack of head-to-head antibiotic comparisons, a recent Cochrane review concluded that current evidence from Randomized Clinical Trials (RCTs) is insufficient to make evidence-based recommendations for the choice for antibiotic to be used, highlighting an important evidence gap.

Efficacy and Safety of Trimodulin (BT588) in Subjects With Severe Community-acquired Pneumonia (sCAP)

The main objective of the trial is to assess the efficacy and safety of trimodulin as adjunctive treatment to standard of care (SoC) compared to placebo plus SoC in adult hospitalized subjects with sCAP on invasive mechanical ventilation (IMV). Other objectives are to determine detailed pharmacokinetic (PK) properties of trimodulin in a PK substudy and to determine its pharmacodynamic (PD) properties.

AntiThrombotic Therapy to Ameliorate Clinical Complications in Community Acquired Pneumonia

This is an international, open-label, stratified randomized controlled trial with Bayesian adaptive stopping rules to compare the effects of therapeutic-dose heparin vs. usual care pharmacological thromboprophylaxis on outcomes in patients admitted to hospital with community acquired pneumonia (CAP).

Discharge Stewardship in Children's Hospitals

The goal of this interventional study is to test if a discharge stewardship bundle is effective at reducing inappropriate antibiotic prescriptions at hospital discharge for children with the three common infections: community-acquired pneumonia (CAP), urinary tract infections (UTI), and skin/soft tissue infections (SSTI). The goals of this study are: * To develop, locally adapt, and implement a discharge stewardship intervention across four geographically diverse children's hospitals. * To measure the impact of the discharge stewardship intervention on antibiotic prescribing and patient outcome for three common pediatric infections. Families who are enrolled in the study will be asked to: * complete a one question wellness track on days 3, 7, and 21 after hospital discharge * complete a brief survey on days 7 and 21 after hospital discharge The study team will conduct interviews with the hospitalists at each of the four participating hospitals to create a "discharge stewardship" bundle. Once the bundle intervention is implemented, the hospitalists will be asked to follow prescribing guidelines for CAP, UTI, and SSTI. They will receive regular group-level feedback reports to show how well they follow the guidelines and motivate the hospitalists to follow the guidelines better.

Clarithromycin Treatment to Prevent Sepsis Progression in CAP (REACT)

The primary objective of the REACT randomized clinical trial (RCT) is to optimize the clinical benefit from adjunctive clarithromycin treatment shown in the ACCESS trial and to provide evidence for the clinical benefit of early start of adjunctive oral clarithromycin guided by suPAR to prevent the progression into sepsis in patients with community-acquired pneumonia (CAP) at risk. This can be achieved by endpoints incorporating clinical benefit with the effect of treatment on the improvement of the immune dysregulation of CAP. The secondary objectives of REACT are to investigate the impact of early adjunctive treatment with clarithromycin on the resolution of CAP at the test-of-cure (TOC) visit.

The Fever Clinic Acute Respiratory Cohort

This prospective cohort study aims to characterize the natural progression and outcomes of acute respiratory infections among patients presenting to fever clinics. At enrollment, patients' clinical symptoms, laboratory findings, and chest imaging data will be collected. Longitudinal follow-up will be conducted to evaluate disease progression, complications, and long-term outcomes. As an observational study, no interventions are involved; all patients receive routine clinical management as directed by their attending physicians. This real-world study design enables the assessment of the natural course of acute respiratory infections and the identification of factors associated with clinical outcomes.

Community-Acquired Pneumonia Diagnosis Using Lung Ultrasound in Emergency Room Adults

Community-Acquired Pneumonia (CAP) is a major problem in Emergency Department (ED). Diagnosis relies on combination of clinical symptoms and results of chest radiography (CR). Patients' management (treatment, support) depends on delay and quality of the diagnosis. However, signs and symptoms are highly aspecific and interpretation of CR is subject to frequent discrepancies. Then diagnosis of CAP may be uncertain; therefore, overdiagnosis is frequent and leads to over-use of antimicrobial therapy; missing diagnosis is also deleterious and delays adequate treatment including antibiotics. CT scan completes CR and helps clinician making properly diagnosis of CAP; obtaining CT in a 4-hour time-lapse allows better diagnosis and management as accurate as an independent expert adjudication committee does. However availability of CT as well as radiation interrogates on the benefit that Lung Ultrasounds (LUS) may have in diagnosis strategy of suspected CAP. LUS is a noninvasive easy-to-use device whose practice is widely endorsed worldwide by emergency medicine associations and societies. Additionally, previous studies advocate for the use of LUS for diagnosis of CAP in the ED. Therefore the Promotor developed a study to compare LUS and CR as a primary imaging for diagnosis of CAP at the ED.

Physical Rehabilitation of Older Persons Following a Community-Acquired Infection Hospitalization - A Randomised-Controlled Trial

Community-acquired infections such as community-acquired pneumonia (CAP) and urinary tract infection (UTI) remain leading causes of hospitalization and death due to infections in older persons in Europe. Hospitalization often results in further disabilities and frailty for older and frail individuals, from which some may never recover. Physical activity is well-established as a cornerstone in the primary prevention and treatment of several noncommunicable diseases. However, there is currently no established rehabilitation model following a pneumonia or other infection, nor is there any evidence to support the impact of rehabilitation on the mental and physical health of older and frail individuals following a pneumonia hospitalization or other infection. The aim of the feasibility study is to evaluate a patient-centered and individualized exercise intervention that is kick-started during hospitalization and continued for 3 months after discharge with video-supervised home-based exercise training to patients hospitalized with CAP or UTI compared to standard care with regard to safety, clinical outcomes, patients' perception, functional ability, organizational aspects, and economic aspects.

Acyclovir in Ventilated Patients With Pneumonia and HSV-1 in BAL

Almost 90 out of 100 people carry herpes simplex viruses (HSV). Once a person has been infected with the herpes viruses, he or she can't get rid of them for the rest of her/his life. For the most part, the viruses are in a dormant state. Only when the immune system is weakened, for example in the case of a serious illness or stress, are the viruses reactivated. They then mainly cause cold sores, which are harmless for healthy people and usually heal without therapy. However, especially in people with a weakened immune system, HSV can also cause serious infections, such as meningitis. In almost every second mechanically ventilated patient in intensive care who has pneumonia, HSV can be detected in the respiratory tract. This is caused by reactivation of the viruses as a result of the severe underlying disease and stress during intensive care therapy. Whether treatment of the herpes viruses (e.g. with acyclovir) is necessary in this situation and helps the patients to cure has not been clarified, especially as acyclovir can also cause side effects such as a deterioration in kidney function. Currently, the physicians decide to treat the herpes viruses in about half of the patients. Several studies have shown that patients for whom the physician decided to treat the viruses survived more often. However, all of these studies looked at the course of the disease only retrospectively and thus are subject to many biases (including physician selection of who receives treatment, missing data). A definitive conclusion as to whether herpesvirus therapy can be recommended cannot be drawn without doubt from these studies. Therefore, the investigators would like to investigate in a randomized controlled trial, i.e. patients are randomly assigned to the experimental (therapy of herpesviruses) or control group (no therapy of herpesviruses), the effect of therapy with acyclovir on survival in ventilated intensive care patients with lower respiratory tract infection (pneumonia) in whom a large amount of HSV was found in the respiratory tract. The goal of the study is to provide clarity on whether therapy will help patients recover.

Azithromycin Versus Doxycycline in Hospitalized Adult Patients With Community Acquired Pneumonia Treated With Beta-lactams

The purpose of this study is to compare effectiveness and safety of Azithromycin versus Doxycycline in adult patients hospitalized with community acquired pneumonia (CAP) treated with Beta-lactams.

The Optimal Antibiotic Treatment Duration for Community-acquired Pneumonia in Adults Diagnosed in General Practice in Denmark (CAP-D)

The aim of this randomised controlled trial is to identify the optimal treatment duration with phenoxymethylpenicillin for community-acquired pneumonia diagnosed in general practice. Eligible participants are adults (≥18 years) presenting in general practice with symptoms of an acute LRTI (i.e., acute illness (≤ 21 days) usually with cough and minimum one other symptom such as dyspnea, sputum production, wheezing, chest discomfort or fever) in whom the GP finds it relevant to treat with antibiotics. Consenting patients who meet all the eligibility criteria will be randomised (1:1:1:1:1) to either three, four, five, six or seven days of treatment with phenoxymethylpenicillin 1.2 MIE four times daily.

Neuromuscular Electrical Stimulation in COPD/Community Acquired Pneumonia

In older adults hospitalized for acute medical conditions, immobility, clinical treatments, and the illness itself contribute to physical deconditioning and delirium, hospital-acquired impairments that increase risk for long-term physical and mental disability, other morbidities, and death. In patients with acute respiratory failure, hospital-acquired functional impairments persist long after hospitalization, due to limited use to rehabilitative interventions in the inpatient or post-acute settings. Exercise and early mobilization interventions are safe and improve physical and cognitive impairments, but there are critical barriers to their widespread implementation in acute care and home settings, including mobility limitations, reduced cardiopulmonary reserve, limited staff, and costs. Thus, there is an unmet need to develop interventions that can be utilized in both the inpatient and home environments to improve functional recovery in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and community-acquired pneumonia (CAP). This study addresses this clinical need and these barriers and will provide important feasibility and acceptability data regarding the utility of neuromuscular electrical stimulation (NMES) administered to lower extremity musculature across inpatient and post-discharge settings to improve functional and cognitive recovery in older adults hospitalized for AECOPD/CAP. Initial NMES sessions will begin during participants' stay at UVM Medical Center and will continue at home after hospital discharge. Study participants will be issued a portable NMES device to take home and instructed on its use. They will receive guidance and oversight on the use of the NMES device and will be asked to perform NMES treatments 6 days per week for 60 minutes per day for 6 weeks. Data will be collected via activity monitor, participant questionnaires and clinical assessments including strength testing and 6-minute-walk-test.

Efficacy and Safety of SR1375 in Adult Patients With CAP

This is a phase 2 study to evaluate the efficacy and safety of SR1375 in hospitalized adult patients with CAP. Patients will receive SR1375 or placebo for 8 weeks. The study duration for each patient is up to 10 weeks.

Noninvasive Support Methods for Acute Respiratory Failure of Community-acquired Pneumonia

This randomized controlled trial aims to compare the efficacy and safety of high-velocity nasal insufflation (HVNI) versus standard noninvasive ventilation (NIV) in adult patients experiencing acute exacerbations of community-acquired pneumonia (CAP) accompanied by hypoxemic respiratory failure. The primary focus is on assessing treatment failure within 48 hours, defined as the need for intubation or death. Secondary outcomes include evaluations of gas exchange parameters, patient comfort levels, duration of ICU stay, and 28-day mortality rates.

Twice Daily Treatment With Amoxicillin for Non-severe Community Acquired Pneumonia.

The aim of this study will be to evaluate whether a twice-daily antibiotic regimen is non-inferior to a thrice-daily regimen for the treatment of non-severe community acquired pneumonia in children presenting at a paediatric Emergency Department (ED).

Awake Prone Positioning of Patients Suffering Community Acquired Pneumonia Requiring Nasal High Flow Therapy

Community acquired pneumonia, in particular when requiring oxygen therapy because of acute hypoxemic respiratory failure and meeting acute respiratory distress syndrome (ARDS) criteria frequently leads to tracheal intubation and poor outcome. Among invasively mechanically ventilated patients with ARDS and presenting a PaO2/FiO2 ratio (arterial partial pressure of oxygen to inspired fraction of oxygen) of less than 150 mmHg, the prone position significantly reduces mortality and represents standard care (Guérin 2013). Among non-intubated COVID-19 patients, a subtype of viral community acquired pneumonia, a recent study showed that awake prone positioning reduces the composite outcome of intubation or death among patients requiring nasal high flow therapy. Furthermore, it favored weaning of nasal high flow therapy. Prone position in patients with non-COVID ARDS treated with high nasal flow was evaluated in 20 patients with predominantly viral pneumonia (Ding 2020) and was associated with improved oxygenation. We hypothesize that prone positioning of patients suffering non-COVID community acquired pneumonia and undergoing nasal high flow therapy can significantly improve outcome by reducing the need for intubation and associated therapies such as sedation and muscle relaxation.

High-dose Inhalations of Nitric Oxide in the Treatment of Pneumonia

This is a multicenter, prospective randomized controlled trial. At least 2 but no more than 5 centers are expected to participate in the study. The primary objective is to test the hypothesis that the addition of high-dose inhaled nitric oxide therapy to standard treatment has a positive effect on the clinical course of pneumonia and the structure and function of cardiopulmonary system. Number of participants: 200, including the subproject NO-PNEUMONIA-CAP - 100 CAP participants, the subproject NO-PNEUMONIA-NP - 100 NP participants. Number of groups: 4 Inhalation of iNO at a dose of 200 ppm for 30 minutes under the control of methemoglobin level (no more than 5%) three times a day if the patient is allocated to the main group. The general course of iNO therapy will last until the pneumonia resolves, but no more than 7 days. Recording of vital signs and safety assessment will be carried out immediately before the initiation of NO therapy and every 15 minutes after its start (pulse, blood pressure, respiratory rate, SpO2, temperature, MetHb level).

Evaluation of Streptococcus Pneumoniae Serotypes Prevalence Using a Urinary Kit

This is an epidemiology study for the prevalence and serotypes of pneumococcus pneumoniae in hospitalized patients with community acquired pneumonia (CAP). The serotypes of the pneumococcus pneumoniae will be determined by a urinary antigen assay. This is a single center, non-interventional observatory study.

Optimizing Care for Children Hospitalized With Community-acquired Pneumonia: Short-course Therapy

Children are commonly hospitalized because of community-acquired pneumonia (CAP). There are multiple high-quality randomized trials of short-course antibiotic therapy (3-5 days of treatment) for adults hospitalized with CAP - but there is very little evidence in children. We intend to do a pilot RCT of short-course (3-5 days) vs standard-duration (8-10 days) antibiotic therapy for children hospitalized for CAP.

Optimizing Care for Children Hospitalized With Community-acquired Pneumonia: Novel Diagnostics

Children are commonly hospitalized because of community-acquired pneumonia. Despite the fact that many of these children have viral disease, a majority is treated with antibiotics. These antibiotics will not accelerate recovery in those with viral pneumonia and can cause harm. We are interested in exploring whether the MeMed BV - a composite biomarker assay - could be used to improve antibiotic prescribing in these children by identifying those who likely have viral disease. This proposal describes a feasibility randomized trial of this diagnostic intervention.

Comparison of Efficacy of Oral Amoxicillin Versus Intravenous Ceftriaxone

The efficacy of oral amoxicillin is considered equal to that of ceftriaxone in community-acquired pneumonia among children. Also, there are some factors that contradict the usage of ceftriaxone, like antibiotic resistance, adverse reactions, drug cost, and the and the chances of IV trauma and infection, which is a major problem in developing countries. Therefore, this study was planned to determine the efficacy of oral amoxicillin compared with intravenous (IV) ceftriaxone in the treatment of uncomplicated ceftriaxone in community acquired pneumonia in children less than 5 years of age.

Fulminant Severe CAP - an Observational Study

Severe community-acquired pneumonia (CAP) represents a major cause of hospital mortality. Among severe CAP cases, some exhibit a rapidly progressive evolution, leading to severe ARDS/acute respiratory failure and septic shock within hours to a few days. This type of pneumonia, known as "fulminant pneumonia," is characterized by its rapid onset and deterioration, often necessitating immediate medical intervention. Despite its severity, the true incidence and optimal treatment for fulminant pneumonia are not well understood. This knowledge gap is due to the lack of attention towards pneumonia as a potential time-dependent illness and the separation of overlapping clinical topics: severe pneumonia, ARDS, and sepsis. In clinical practice, pneumonia is the most frequent cause of both ARDS and sepsis. However, these conditions are often considered separately, combining ARDS and sepsis from various extra-pulmonary causes with those originating from pneumonia. The COVID-19 pandemic, with its vast number of severe CAP cases in a short period, has highlighted the existence of fulminant pneumonias, underscoring the need for further investigation. Recent randomized clinical trials (RCTs) and experiences from COVID-19 have suggested that early and prolonged corticosteroid administration can reduce mortality in patients with severe SARS-CoV-2 infection and severe CAP/ARDS of bacterial origin. The aim of this observational study is to analyze the rate of fulminant pneumonia and assess the impact of early corticosteroid treatment in a multicentric population of hospitalized patients with severe pneumonia.

Stopping Pneumonia Antibiotherapy Regimen Early

The hypothesis for this trial is that an antibiotic strategy for the management of non-severe community-acquired alveolar pneumonia in children aged 3 to 59 months, including amoxicillin 80-100 mg/kg/day for at least 3 days in case of rapid response and 5 days in case of delayed response, would not be inferior to current French recommendations (antibiotic therapy for 5 days in case of rapid response and 7 days in case of delayed response) in terms of treatment of failure rate at 7 days.

Fluad vs. Fluzone High-Dose Vaccine Effectiveness Among Adults ≥65 Years

This study will evaluate the relative vaccine effectiveness of quadrivalent adjuvanted inactivated influenza vaccine (aIIV4) versus quadrivalent high-dose inactivated influenza vaccine (HD-IIV4) in preventing polymerase chain reaction (PCR)-confirmed influenza and influenza-related outcomes in adults ≥65 years of age during the 2023/24 and 2024/25 influenza seasons. The study is an observational study conducted at Kaiser Permanente Northern California (KPNC), an integrated health care system in the United States.