Efficacy and safety of colchicine treatment in patients with COVID-19: A prospective, multicenter, randomized clinical trial.

Colchicine has shown clinical benefits in the management of COVID-19 via its anti-inflammatory effect. However, the exact role of colchicine in COVID-19 patients is unknown. The current clinical trial was performed on 202 patients with moderate to severe COVID-19. Patients were randomly assigned in a 1:1 ratio to receive up to a 3-day course of 0.5 mg colchicine followed by a 12-day course of 1 mg colchicine in combination with standard care or a 15-day course of standard care. Among 202 randomized patients, 153 completed the study and received colchicine/standard care or continued standard care (M age, 54.72 [SD, 15.03] years; 93 [63.1%] men). On day 14, patients in the colchicine/standard care group had significantly higher odds of a better clinical status distribution on chest CT evaluation (p = .048). Based on NYHA classification, the percentage change of dyspnea on day 14 between groups was statistically significant (p = .026), indicating a mean of 31.94% change in the intervention group when compared with 19.95% in the control group. According to this study, colchicine can improve clinical outcomes and reduce pulmonary infiltration in COVID-19 patients if contraindications and precautions are considered and it is prescribed at the right time and in appropriate cases.

A randomized double-blinded placebo-controlled clinical trial on protective effects of pentoxifylline on gentamicin nephrotoxicity in infectious patients.

BACKGROUND AND OBJECTIVE: Renal toxicity has limited gentamicin use in clinical practice. The aim of the present clinical trial was to assess the possible nephroprotective effects of pentoxifylline (PTX) against gentamicin nephrotoxicity. MATERIALS AND METHODS: A multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted on patients who had the indication for systemic gentamicin for at least 7 days. Sixty people were selected and randomly assigned. For patients in the intervention and control groups, 400 mg PTX sustained release tablet and placebo were given orally three times daily, respectively. Demographic, clinical, laboratory, and therapeutic information of patients were recorded. malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) levels in serum were measured on days 0 and 7. RESULTS: The incidence of nephrotoxicity in the placebo group was 19.6 times higher than that in the PTX group (OR = 19.6, 95%CI = 3.08-114.32; P value = 0.001). The mean ± SD time onset of ATN was 4.00 ± 2.32 and 5.58 ± 1.59 days in PTX and placebo recipients, respectively (P value < 0.001). No significant differences were observed for hypokalemia, hypomagnesemia, potassium and magnesium wasting between the two groups. The mean ± SD levels of serum MDA and TNF-α at day 7 were significantly lower in the PTX compared to those in the placebo group (P value < 0.001 for both indexes). CONCLUSION: The co-administration of 400 mg PTX orally three times daily along with gentamicin was both well-tolerated and effective in preventing the nephrotoxicity of gentamicin in patients with different infectious diseases.

Efficacy and safety of Levamisole treatment in clinical presentations of non-hospitalized patients with COVID-19: a double-blind, randomized, controlled trial.

BACKGROUND: Levamisole has shown clinical benefits in the management of COVID-19 via its immunomodulatory effect. However, the exact role of Levamisole effect in clinical status of COVID-19 patients is unknown. We aimed to evaluate the efficacy of Levamisole on clinical status of patients with COVID-19 during their course of the disease. METHODS: This prospective, double-blind, randomized controlled clinical trial was performed in adult patients with mild to moderate COVID-19 (room-air oxygen saturation > 94%) from late April 2020 to mid-August 2020. Patients were randomly assigned to receive a 3-day course of Levamisole or placebo in combination with routine standard of care. RESULTS: With 25 patients in each arm, 50 patients with COVID-19 were enrolled in the study. Most of the study participants were men (60%). On days 3 and 14, patients in Levamisole group had significantly better cough status distribution when compared to the placebo group (P-value = 0.034 and 0.005, respectively). Moreover, there was significant differences between the two groups in dyspnea at follow-up intervals of 7 (P-value = 0.015) and 14 (P-value = 0.010) days after receiving the interventions. However, no significant difference in fever status was observed on days 1, 3, 7, and 14 in both groups (P-value > 0.05). CONCLUSION: The results of the current study suggest that Levamisole may improve most of clinical status of patients with COVID-19. The patients receiving Levamisole had significantly better chance of clinical status including cough and dyspnea on day 14 when compared to the placebo. However, the effect-size of this finding has uncertain clinical importance. TRIAL REGISTRATION: The trial was registered as IRCT20190810044500N7 (19/09/2020).

Evaluation of the efficacy and safety of inhaled magnesium sulphate in combination with standard treatment in patients with moderate or severe COVID-19: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: Basic and clinical studies have shown that magnesium sulphate ameliorates lung injury and controls asthma attacks by anti-inflammatory and bronchodilatory effects. Both intravenous and inhaled magnesium sulphate have a clinical impact on acute severe asthma by inhibition of airway smooth muscle contraction. Besides, magnesium sulphate can dilate constricted pulmonary arteries and reduce pulmonary artery resistance. However, it may affect systemic arteries when administered intravenously. A large number of patients with covid-19 admitted to the hospital suffer from pulmonary involvement. COVID-19 can cause hypoxia due to the involvement of the respiratory airways and parenchyma along with circulatory impairment, which induce ventilation-perfusion mismatch. This condition may result in hypoxemia and low arterial blood oxygen pressure and saturation presented with some degree of dyspnoea and shortness of breath. Inhaled magnesium sulphate as a smooth muscle relaxant (natural calcium antagonist) can cause both bronchodilator and consequently vasodilator effects (via a direct effect on alveolar arterioles in well-ventilated areas) in the respiratory tract. We aim to investigate if inhaled magnesium sulphate as adjuvant therapy to standard treatment can reduce ventilation-perfusion mismatch in the respiratory tract and subsequently improve arterial oxygen saturation in hospitalized patients with COVID-19. TRIAL DESIGN: A multi-centre, open-label, randomised controlled trial (RCT) with two parallel arms design (1:1 ratio) PARTICIPANTS: Patients aged 18-80 years hospitalized at Masih Daneshvari Hospital and Shahid Dr. Labbafinejad hospital in Tehran and Shahid Sadoughi Hospital in Yazd will be included if they meet the inclusion criteria of the study. Inclusion criteria are defined as 1. Confirmed diagnosis of SARS-CoV-2 infection based on polymerase chain reaction (PCR) of nasopharyngeal secretions or clinical manifestations along with chest computed tomography (chest CT) scan 2. Presenting with moderate or severe COVID-19 lung involvement confirmed with chest CT scan and arterial oxygen saturation below 93% 3. Length of hospital stay ≤48 hours. Patients with underlying cardiovascular diseases including congestive heart failure, bradyarrhythmia, heart block, the myocardial injury will be excluded from the study. INTERVENTION AND COMPARATOR: Participants will be randomly divided into two arms. Patients in the intervention arm will be given both standard treatment for COVID-19 (according to the national guideline) and magnesium sulphate (5 cc of a 20% injectable vial or 2 cc of a 50% injectable vial will be diluted by 50 cc distilled water and nebulized via a mask) every eight hours for five days. Patients in the control (comparator) arm will only receive standard treatment for COVID-19. MAIN OUTCOMES: Improvement of respiratory function and symptoms including arterial blood oxygen saturation, dyspnoea (according to NYHA functional classification), and cough within the first five days of randomization. RANDOMISATION: Block randomisation will be used to allocate eligible patients to the study arms (in a 1:1 ratio). Computer software will be applied to randomly select the blocks. BLINDING (MASKING): The study is an open-label RCT without blinding. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The trial will be performed on 100 patients who will be randomly divided into two arms of control (50) and intervention (50). TRIAL STATUS: The protocol is Version 5.0, January 05, 2021. Recruitment of the participants started on July 30, 2020, and it is anticipated to be completed by February 28, 2021. TRIAL REGISTRATION: The trial was registered in the Iranian Registry of Clinical Trials (IRCT) on July 28, 2020. It is available on https://en.irct.ir/trial/49879 . The registration number is IRCT20191211045691N1. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Ascorbic Acid Significantly Decreases Creatine Kinase Plasma Levels in an Animal Model of Statin/Fibrate-Induced Myopathy.

BACKGROUND: Myopathy is one of the side effects of lipid-lowering drugs, especially statins and particularly when combined with a fibrate. To diagnose myopathy and determine its severity, the plasma levels of three enzymes, creatine kinase (CK), aldolase, and lactate dehydrogenase (LDH), are routinely measured. Physical exercise can aggravate the statin-associated muscular disease. The question is whether antioxidants like ascorbic acid (Vit. C) can prevent such myopathy. METHODS: In this experiment, a combination of atorvastatin (ATV, 80 mg/kg/day) and gemfibrozil (GMF, 1000 mg/kg/day) orally for 10 days as well as exercise as forced swimming on days 8, 9, and 10 were used to induce myopathy. Ascorbic acid (50 mg/kg/day, orally) was added to ATV/GMF plus exercise regimen throughout the 10 days in the treatment group. Mean blood levels of CK, aldolase, and LDH were measured in addition to swimming tolerance times. RESULTS: There was a significantly higher swimming tolerance time (P < 0.05) and lower CK levels (P < 0.01) in rats receiving ATV/GMF/Vit. C plus exercise compared with rats not taking Vit. C. LDH and aldolase did not decrease significantly. CONCLUSION: The results of this study showed that Vit. C can be effective in preventing myopathy caused by fat-lowering drugs.