Clinical Research Directory

Effect of Low-Dose Versus High-Dose Alpha-Lipoic Acid on Oxidative Stress, Inflammation, and Clinical Outcomes in Acute Exacerbations of Chronic Obstructive Pulmonary Disease

Chronic Obstructive Pulmonary Disease (COPD) is a progressive inflammatory lung disease characterized by persistent airflow limitation and enhanced oxidative stress. Acute exacerbations of COPD (AECOPD) significantly increase morbidity, accelerate lung function decline, and worsen clinical outcomes. Oxidative stress plays a central role in AECOPD pathophysiology by amplifying inflammation through mediators such as IL-8 and TNF-α, leading to airway injury and impaired gas exchange. Alpha Lipoic Acid (ALA) is a potent antioxidant and anti-inflammatory agent that scavenges reactive oxygen species, regenerates endogenous antioxidants, and modulates redox-sensitive inflammatory pathways. Although preclinical evidence supports its protective role in respiratory diseases, no randomized clinical trial has evaluated ALA in AECOPD or compared different dosing strategies. Aim This study aims to evaluate and compare the effects of low-dose (600 mg/day) versus high-dose (1200 mg/day) ALA on oxidative stress markers, inflammatory biomarkers, clinical recovery, pulmonary oxygenation, gas exchange, and safety in patients with AECOPD. Methods This is a prospective, double-blind, randomized controlled trial conducted in the ICU at El Matareya Teaching Hospital. Adult patients (40-70 years) with confirmed COPD and frequent exacerbations were randomized (1:1:1) into three groups: Group A: Standard therapy + placebo Group B: Standard therapy + 600 mg/day oral ALA Group C: Standard therapy + 1200 mg/day oral ALA All patients received guideline-based AECOPD management according to GOLD recommendations, including bronchodilators, systemic corticosteroids, antibiotics (when indicated), oxygen therapy, and ventilatory support as needed. Assessments Baseline and Day 10 evaluations included: Primary Outcomes: Oxidative stress marker: Malondialdehyde (MDA) Inflammatory markers: Interleukin-8 (IL-8) and C-reactive protein (CRP) Secondary Outcomes: Time to clinical stability ICU and hospital length of stay Need for non-invasive or invasive ventilation Early relapse (14 days) and 30-day readmission Gas Exchange: ABGs (pH, PaO₂, PaCO₂, P/F ratio) Patient-Reported Outcomes: COPD Assessment Test (CAT) and mMRC dyspnea scale Safety: Monitoring for adverse effects including gastrointestinal symptoms, hypoglycemia, dizziness, and hypersensitivity reactions.

Intravenous Alpha-1 Antitrypsin for Hospitalized Patients With COPD Exacerbations (AECOPD Study)

Intravenous augmentation therapy with purified preparations of AAT (Alpha1-antitrypsin) derived from human plasma is a well consolidated specific therapeutic option to treat the severe deficient state of AAT. Prolastin is used to restore the balance between AAT and elastases in the lung and consequently to prevent a further deterioration in the pulmonary emphysema. Recently, in patients with COVID-19, without genetically lowered AAT levels with moderate to severe ARDS, treatment with AAT was demonstrated to be safe, feasible, and biochemically efficacious as an anti-inflammatory therapeutic therapy. The aim of the study, based on biological plausibility, is to evaluate the safety and efficacy (from a biological perspective) of the administration of intravenous plasma-purified AAT as an anti-inflammatory treatment for patients admitted to hospital because of a COPD exacerbation leading to an acute or an acute on chronic respiratory failure. Thirty-six adult patients hospitalized because of a COPD exacerbation leading to an acute or an acute on chronic respiratory failure will be enrolled by the two sites involved in the study, the Pneumology Unit of Fondazione IRCCS Policlinico San Matteo (Pavia, Italy) and the Pneumology Unit of IRCCS Istituto Clinico Humanitas, Rozzano (Milano, Italy). Participants will be randomized 2:1 in the active treatment group (standard treatment + IV administration of Prolastin) or in the placebo group (standard treatment+ IV administration of 0.9% sodium chloride). To address the clinical question from a biological perspective, we will investigate the decrease in inflammatory markers in the active treated group in comparison with the placebo group. The primary objective is to demonstrate a significant reduction in systemic inflammation by IV Prolastin administered once at 120 mg per kilogram of body weight in patients with moderate to severe AECOPD, as assessed by the change in plasma concentration of IL6 at 7 days after randomization, in the active treatment group with respect to placebo group. Secondary outcomes are: 1. Difference in change in plasma concentration of IL-1b, IL-5, IL-8, IL-10, and soluble TNF receptor 1 (sTNFR1), CRP at 7 days after randomization. 2. Differences in AAT antielastase activity, the amount of active elastase, the AAT levels in serum at baseline and at 7 days after randomization. 3. Difference in treatment failure rate. Treatment failure is a composite endpoint of need for either NIV or CPAP or need of ETI or need of transfer to ICU or in-hospital death after randomization 4. Impact of AECOPD on overall health, daily life, and perceived well-being in patients with obstructive airways disease by the change of St. George's Respiratory Questionnaire (SGRQ) score from Day 7 to follow-up (30 days after hospital discharge). 5. Differences in type and number of AEs and SAEs in the two groups The expected duration of subject participation is from randomization to 30 days after hospital discharge, with a follow up phone contact.

MxA and CRP-Guided Use of Antimicrobial Agents for AECOPD

This randomized controlled trial will investigate the clinical impact of Myxovirus Resistance A (MxA) and C-Reactive Protein (CRP)-guided antimicrobial treatment compared to usual care in outpatients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD).