almitrine / Public Assistance - Paris Hospitals - LARVOL DELTA

Chronic Mountain Sickness: A Comprehensive Review of Current Management and Proposals for Novel Therapies. (PubMed, High Alt Med Biol) - "Acetazolamide, enalapril, and medroxyprogesterone have lowered hematocrit and alleviated symptoms in human trials...Methylxanthines, adrenergic blockers, almitrine, and dopamine antagonists showed promise in murine and/or short-term human trials, highlighting the need for further long-term human trials...Topiramate may stimulate ventilation via acid-base modulation, thus providing therapeutic value. Similarly, the effect of aspirin and caffeine on ventilation may provide a low-cost, accessible intervention."

Journal • Review • Cardiovascular • Congestive Heart Failure • Fatigue • Heart Failure • Hematological Disorders • Hypertension • Polycythemia Vera • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Almitrine in COVID-19 Patients With ARDS Treated by HFNO (clinicaltrials.gov) - P=N/A | N=62 | Completed | Sponsor: Centre Hospitalier Universitaire de Nice | Recruiting ➔ Completed

Trial completion • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

Repurposing COVID-19 Compounds (via MMV COVID Box): Almitrine and Bortezomib Induce Programmed Cell Death in Trypanosoma cruzi. (PubMed, Pathogens) - "Current therapies, such as benznidazole and nifurtimox, present challenges, including their toxicity, side effects, and inefficacy in the chronic phase. The potential to induce controlled cell death of these two compounds in T. cruzi suggests they are promising candidates for further research. This study reinforces drug repurposing as a viable approach to discovering novel treatments for neglected tropical diseases like Chagas disease."

Journal • Infectious Disease • Malaria • Novel Coronavirus Disease

Anti-COVID Drugs (MMV COVID Box) as Leishmanicidal Agents: Unveiling New Therapeutic Horizons. (PubMed, Pharmaceuticals (Basel)) - "Our study revealed that bortezomib, almitrine, and terconazole induced a significant decrease in mitochondrial membrane potential, while the above compounds and ABT239 induced plasma permeability alterations, chromatin condensation, and reactive oxygen species accumulation, indicating early apoptosis in Leishmania amazonensis promastigotes, preventing inflammatory responses and tissue damage, thereby improving patient outcomes. In conclusion, our study identifies bortezomib as a promising aspirant for leishmaniasis treatment, demonstrating potent antiparasitic activity, favorable pharmacokinetics, and low toxicity. These findings emphasize the potential repurposing of existing drugs for neglected diseases and highlight the importance of the COVID Box in drug discovery against tropical diseases."

Journal • Infectious Disease • Inflammation • Novel Coronavirus Disease

Unraveling the impact of nitric oxide, almitrine, and their combination in COVID-19 (at the edge of sepsis) patients: a systematic review. (PubMed, Front Pharmacol) - "Well-designed high-quality studies are needed for establishing a stronger quality of evidence. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=367667, identifier CRD42022367667."

Clinical • Review • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Septic Shock

Associations between genetically predicted plasma protein levels and Alzheimer's disease risk: a study using genetic prediction models. (PubMed, Alzheimers Res Ther) - "Our study provides additional insights into the underlying mechanisms of AD and potential therapeutic strategies."

Journal • Alzheimer's Disease • CNS Disorders • ATP1A1

Repurposing the Medicines for Malaria Venture's COVID Box to discover potent inhibitors of Toxoplasma gondii, and in vivo efficacy evaluation of almitrine bismesylate (MMV1804175) in chronically infected mice. (PubMed, PLoS One) - "This was determined by quantifying the RNA of living parasites using real-time PCR. The presented results suggest that almitrine may be a promising drug candidate for additional experimental studies on toxoplasmosis and provide further evidence of the potential of the MMV collections as a valuable source of drugs to be repositioned for infectious diseases."

Journal • Preclinical • Infectious Disease • Malaria • Novel Coronavirus Disease

Targeting a Non-Opioid Signaling Pathway to Reverse Opioid-Induced Respiratory Depression (CPDD 2023) - "1 Preclinical - In Vitro Aim: The opioid epidemic is a public health crisis with growing numbers of overdose deaths caused by ultrapotent synthetic opioids like fentanyl. The carotid body is a chemosensory organ that senses low blood oxygen to increase ventilation within seconds. Small molecule drugs that stimulate the carotid body (doxapram, almitrine, and GAL-021) have been shown to reverse opioid-induced respiratory depression, but these drugs act on molecules expressed broadly in many tissues and have deleterious side effects or ceiling effects that limit their use. We previously identified a G protein-coupled receptor (mouse Olfr78/human OR51E2) that mediates sensory signaling in the carotid body."

Addiction (Opioid and Alcohol) • CNS Disorders • Depression • Mood Disorders • Psychiatry

Impact of pharmacological interventions on intrapulmonary shunt during one-lung ventilation in adult thoracic surgery: a systematic review and component network meta-analysis. (PubMed, Br J Anaesth) - "Adding NO or almitrine to propofol anaesthesia reduced intrapulmonary shunt during one-lung ventilation. Halogenated anaesthetics increased shunt in comparison with propofol. The effects of NO, iloprost, and dexmedetomidine should be investigated in future research. NO results constitute a research hypothesis currently not backed by any direct evidence. The clinical availability of almitrine is limited."

Journal • Retrospective data • Review • Surgery • Anesthesia

Use of almitrine in spontaneously breathing patients with COVID-19 treated with high-flow nasal cannula oxygen therapy and with persistent hypoxemia. (PubMed, Respir Res) - "Almitrine could be an interesting therapy in spontaneously breathing patients with COVID-19 treated with HFNO and with persistent hypoxemia, given its effects on oxygenation without serious adverse effects regardless of the CT-Scan pattern, and potentially on intubation rate. These preliminary results need to be confirmed by further randomized studies."

Journal • Acute Respiratory Distress Syndrome • Cardiovascular • Heart Failure • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

Efficacy of almitrine as a rescue therapy for refractory hypoxemia in COVID and non-COVID acute respiratory distress syndrome. A retrospective monocenter study. (PubMed, Minerva Anestesiol) - "Our study reports a highly variable response to almitrine infusion in ARDS patients with refractory hypoxemia. Independent factors associated with a reduced oxygenation response to almitrine infusion were: Covid ARDS, concomitant use of norepinephrine, and non-invasive ventilatory strategy."

Journal • Retrospective data • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

Effect of intravenous almitrine on intubation or mortality in patients with COVID-19 acute hypoxemic respiratory failure: A multicentre, randomised, double-blind, placebo-controlled trial. (PubMed, EClinicalMedicine) - P3 | "In patients with COVID-19 acute hypoxemic respiratory failure, low-dose almitrine failed in reducing the need for MV or death at day 7. Programme Hospitalier de Recherche Clinique (PHRC COVID 2020) funded by the French Ministry of Health, Les Laboratoires Servier (Suresnes, France) providing the study drug free of charge."

Journal • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

Drug Repurposing Based on Protozoan Proteome: In Vitro Evaluation of In Silico Screened Compounds against Toxoplasma gondii. (PubMed, Pharmaceutics) - "gondii activity in the nanomolar range (almitrine, bortezomib, and fludarabine), and ten compounds demonstrated anti-T. gondii activity in the micromolar range (digitoxin, digoxin, doxorubicin, fusidic acid, levofloxacin, lomefloxacin, mycophenolic acid, ribavirin, trimethoprim, and valproic acid). Almitrine demonstrated a Selectivity Index (provided by the ratio between the Half Cytotoxic Concentration against human foreskin fibroblasts and the Half Effective Concentration against T. gondii tachyzoites) that was higher than 47, whilst being considered a lead compound against T. gondii. Almitrine showed interactions with the Na/K ATPase transporter for Homo sapiens and Mus musculus, indicating a possible mechanism of action of this compound."

Journal • Preclinical • Infectious Disease

Aromatic or Hetero-aromatic Directly Attached Tri and Tetrasubstituted Methanes: New Chemical Entities as Anti-infectives. (PubMed, Curr Med Chem) - "Properties of repurposed TRSMs like Almitrine, Ifenprodil, Baricitinib and Remdesivir with their recent progress in Covid-19 therapeutics with their mode of action are also delineated. This perspective is expected to deliver a user guide and reference source for scientists, researchers and academicians in pursuing newly designed TRSMs as therapeutics."

Journal • Infectious Disease • Novel Coronavirus Disease

AIRVM-COVID: Efficacy of Intravenous Almitrine in Reducing the Need for Mechanical Ventilation in Patients With Hypoxemic Acute Respiratory Failure Due to Covid-19-related Pneumonia (clinicaltrials.gov) - P3 | N=181 | Completed | Sponsor: Assistance Publique - Hôpitaux de Paris | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

Ventilation/Perfusion Mismatch: A Novel Target for COPD Treatment. (PubMed, Chest) - "We review the conflicting evidence supporting current treatments for gas-exchange inefficiency and exercise tolerance which act primarily on VA (bronchodilators, anti-inflammatory medications) or Qc (oral and inhaled vasodilators, almitrine and supplemental oxygen). Finally, to address the current knowledge and health-care gaps, we propose two independent clinical research foci that may lead to a better understanding of the role of pulmonary gas-exchange efficiency and activity-related dyspnea in COPD: 1) improved and deeper phenotyping of COPD patients with VA/Qc abnormalities, and, 2) evaluation of existing and novel pharmacological treatments in relation to improved gas-exchange inefficiency, exertional dyspnea, and exercise tolerance across the spectrum of COPD severity."

Journal • Review • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Covid-19 and Artificial Intelligence: Genome sequencing, drug development and vaccine discovery. (PubMed, J Infect Public Health) - "The growth of AI techniques in health care opened a broad gate for discovering the genomic sequences of the COVID-19 virus and the VOC. AI helps also in the development of vaccines and drugs (including drug repurposing) to obtain potential preventive and therapeutic agents for controlling the COVID-19 pandemic."

Journal • Review • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Almitrine in COVID-19 Patients With ARDS Treated by HFNO (clinicaltrials.gov) - P=N/A | N=50 | Recruiting | Sponsor: Centre Hospitalier Universitaire de Nice

New trial • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • PCR

AIRVM-COVID: Efficacy of Intravenous Almitrine in Reducing the Need for Mechanical Ventilation in Patients With Hypoxemic Acute Respiratory Failure Due to Covid-19-related Pneumonia (clinicaltrials.gov) - P3; N=181; Active, not recruiting; Sponsor: Assistance Publique - Hôpitaux de Paris; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

AIRVM-COVID: Efficacy of Intravenous Almitrine in Reducing the Need for Mechanical Ventilation in Patients With Hypoxemic Acute Respiratory Failure Due to Covid-19-related Pneumonia (clinicaltrials.gov) - P3; N=212; Recruiting; Sponsor: Assistance Publique - Hôpitaux de Paris; Trial completion date: Jul 2021 ➔ Oct 2021; Trial primary completion date: Jul 2021 ➔ Oct 2021

Clinical • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

Use of Almitrine and Inhaled Nitric Oxide in ARDS Due to COVID-19. (PubMed, Front Med (Lausanne)) - "This combination may be of interest when first-line therapies fail to restore adequate oxygenation. These findings argue for an impaired pulmonary hypoxic vasoconstriction in these patients."

Journal • Acute Respiratory Distress Syndrome • Critical care • Hypertension • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Role of almitrine bismesylate in managing refractory hypoxemia in COVID19 acute respiratory distress syndrome. (PubMed, Saudi J Anaesth) - No abstract available

Journal • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

AIRVM-COVID: Efficacy of Intravenous Almitrine in Reducing the Need for Mechanical Ventilation in Patients With Hypoxemic Acute Respiratory Failure Due to Covid-19-related Pneumonia (clinicaltrials.gov) - P3; N=212; Recruiting; Sponsor: Assistance Publique - Hôpitaux de Paris; Trial completion date: Dec 2020 ➔ Jul 2021; Trial primary completion date: Dec 2020 ➔ Jul 2021

Clinical • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

BRIEF-Oxford Says Clinical Trial Commenced This Week To Test If Drug Almitrine Can Help People Seriously Ill With COVID-19 (Reuters) - "Oxford University Says drug trial that could improve respiratory recovery from COVID-19 now underway; Oxford University -clinical trial commenced this week to test if drug almitrine can help people seriously ill with covid-19 to recover from disease; Oxford-Almitrine to be administered orally over 7-day period to determine its effectiveness in reducing need for other forms of ventilatory support."

Trial status • Infectious Disease • Novel Coronavirus Disease

To determine whether administration of almitrine bismesylate can ameliorate hypoxaemia in Covid-19 and augment effectiveness of supplementary oxygen therapy and respiratory support. (clinicaltrialsregister.eu) - P4; N=112; Ongoing; Sponsor: University of Oxford / Clinical Trials and Research Governance

New P4 trial • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases