Dopram (doxapram) / Kissei - LARVOL DELTA

Impact of changing open-label drug prescription policies on consent rates in a neonatal trial: a quasinatural experiment. (PubMed, Arch Dis Child Fetal Neonatal Ed) - "Restricting open-label access to an off-label investigational drug can substantially increase parental consent and patient enrolment in neonatal RCTs. To promote both ethical recruitment and optimal enrolment, future trials should explicitly discuss equipoise in each contributing unit and align local clinical practices with the trial design prior to initiation."

Journal • Critical care

Study to Investigate the Safety, Tolerability and Pharmacokinetics of QEV-817 Oral Suspension (clinicaltrials.gov) - P1 | N=8 | Completed | Sponsor: Quivive Pharma, Inc. | Not yet recruiting ➔ Completed | Trial completion date: Dec 2024 ➔ Nov 2025 | Trial primary completion date: Dec 2024 ➔ Aug 2025

Trial completion • Trial completion date • Trial primary completion date

Pairing ampakine with brief hypoxia evokes phrenic neuroplasticity via a spinal NMDA receptor mediated mechanism. (PubMed, Function (Oxf)) - "Pairing ampakine CX717 with brief moderate or severe hypercapnia failed to produce pMF. Pairing doxapram, a respiratory stimulant, with hypoxia did not produce pMF...In contrast, the NMDA-R blocker MK-801 prevented pMF when administered before but not after A-H...We conclude that the mechanism driving sustained increases in phrenic motor output after A-H is independent of spinal adenosine or serotonin receptor activation, but requires spinal NMDA-R activation for the induction, but not maintenance of A-H pMF. Ampakine pretreatment may be useful to increase the efficacy of hypoxia-based rehabilitation paradigms after SCI, particularly since clinical trials report a substantial number of "low-responders"."

Journal • Anesthesia • CNS Disorders • Orthopedics

the Effect of Doxapram on Diaphragmatic Excursion(DE) During Weaning From Mechanical Ventilation. (clinicaltrials.gov) - P4 | N=60 | Not yet recruiting | Sponsor: Kasr El Aini Hospital

New P4 trial

The present and future of antiarrhythmic drugs. (PubMed, JRSM Cardiovasc Dis) - "Flecainide, propafenone, and dronedarone have demonstrated their reliable efficacy and safety, even in patients with structural heart disease, which should allow clinicians to reduce their reliance on amiodarone. Previous concerns regarding the proarrhythmic risk of dofetilide and ibutilide are currently managed through careful patient selection and adequate QT interval monitoring. Novel targeted AADs are advancing through the development pipeline, of which etripamil and landiolol have already been approved. Other emerging drugs, such as SK channel blockers (AP30663 and AP31969), RyR2 blockers, CaMKII inhibitors, and TASK-1 blockers (doxapram), are aligned with the new paradigm of atrial fibrillation that focuses on triggers and re-entry...Developing concepts such as atrial cardiomyopathy allows clinicians to characterize substrate objectively, in order to assess disease severity and individualize antiarrhythmic treatment. The future of antiarrhythmic therapy will be..."

Journal • Atrial Fibrillation • Cardiomyopathy • Cardiovascular • Heart Failure

Doxapram Exposure Was Not Associated With Adverse Neurodevelopmental Outcomes in Very Low Birth Weight Infants: A Monocentric Retrospective Cohort Study. (PubMed, Acta Paediatr) - "Doxapram exposure was not associated with adverse neurodevelopmental outcomes in VLBWI within the investigated dosage range, although definitive conclusions on drug safety cannot be drawn from medium-sized cohorts and confirmation in prospective randomised studies is required."

Journal • Retrospective data

Role Of Non-Invasive Ventilation Failure In Initiating Preterm Lung Disease (PAS 2026) - "Lambs in NIV-failure were intubated at mean (SD) 29 (12) min compared to 50 (7) min for NIV-PPV. As expected, the NIV-failure group had lower pH, higher PaCO2, worse oxygenation (Figure 1) and greater caffeine and doxapram needs, but prior to intubation less respiratory effort ( Table 1). Alveolar morphology was similar, but lung injury was greater in the NIV-failure group (Table 1)."

Non-invasive • Prematurity • Metabolic Disorders • Pulmonary Disease • Respiratory Diseases

Mechanisms Of Preterm Lung Injury During Non-Invasive Respiratory Support (PAS 2026) - "All lambs received caffeine and doxapram... Gas exchange, cerebral oxygenation, respiratory rate, Poes characteristics (Table 1) and alveolar morphology were similar (Figure 1). Dependent lung injury was greater in SIPPV lambs. Proteome alterations were lung region- and ventilation strategy-specific with the greatest change observed in SIPPV non-dependent lung (Table 1)."

Non-invasive • Prematurity • Respiratory Diseases

Doxapram for Apnoea of Prematurity (DoxAPrem) Dosage Study (ANZCTR) - P2 | N=32 | Completed | Sponsor: University of Auckland | Recruiting ➔ Completed

Trial completion

Dosing practices of caffeine therapy for apnoea of prematurity: a retrospective single-centre observational study. (PubMed, BMJ Paediatr Open) - "Caffeine therapy in this unit showed marked variability in dosing, discontinuation and recommencement, highlighting the individualised nature of bedside decision-making, which may reflect clinical response to therapy."

Journal • Observational data • Retrospective data • Critical care

Pharmacological treatment for apnoea of prematurity-the need for an individualised approach. (PubMed, Front Pediatr) - "Caffeine (or in some developing countries, aminophylline or theophylline) is usually given as first-line treatment, whereas doxapram is sometimes used as an adjunct therapy. We propose potential pharmacodynamic biomarkers and explore avenues for future research which will enable the testing and translation of these biomarkers for use in the neonatal unit. A personalised approach for apnoea treatment is essential to mitigate the negative short and long-term effects of both apnoea and its treatment in premature infants, ensuring that treatment can be provided at the right time and with the correct dose."

Journal • Review

Comparative Effects of Aminophylline, Caffeine, and Doxapram in Hypoxic Neonatal Dogs Born by Cesarean Section. (PubMed, Animals (Basel)) - "Aminophylline, caffeine, and doxapram supported postnatal resuscitation in hypoxic neonatal puppies; however, caffeine demonstrated superior improvement in Apgar recovery, suggesting its potential as a preferred pharmacological adjunct in neonatal canine resuscitation protocols."

Journal • Anesthesia • CNS Disorders • Depression • Obstetrics • Psychiatry • TNNI3

Oral doxapram for apnea of prematurity: A randomized dosage trial. (PubMed, J Perinatol) - P2 | "Oral doxapram is feasible in very preterm infants with improvements in oxygenation and ventilation. Lower doses (12 mg/kg/6 h) are sufficient in most infants."

Journal

Role of Spontaneous Effort During Mechanical Ventilation on Lung Injury in Preterm Lambs. (PubMed, Am J Respir Crit Care Med) - "Breathing was supported with caffeine, doxapram and stimulation... Different breathing efforts during PPV support of the preterm lung creates complex lung states, each with unique and measurable injury events. This offers the potential to develop lung protective strategies that target minimising breathing-related injury."

Journal • Respiratory Diseases

Doxapram May Improve Reliability of Oxygen Supplementation for Treatment of Anesthesia-Induced Hypoxemia of Moose (Alces alces). (PubMed, J Wildl Dis) - "Drug-induced hypoxemia can occur with the immobilization of free-living moose (Alces alces). We describe the physiologic response of 12 adult females immobilized with thiafentanil and xylazine and exhibiting clinical signs of hypoxemia before (pretreatment) and after (posttreatment) nasal oxygen supplementation (4 L/min) with or without intravenous doxapram."

Journal • Anesthesia

Management of apnoea in extremely preterm infants - a European Survey. (PubMed, Neonatology) - "All NICUs reported using caffeine citrate, with 102 centres (23%) starting it in the delivery room (DR). Despite consistency in the dosing and weaning of caffeine, there is much variation in the management of apnoea in preterm infants across Europe. Future research should focus on timing and dosage of caffeine, the use of doxapram, and strategies for optimising non-invasive respiratory support."

Journal • Critical care

Comparison of the Clinical Efficacy, Adverse Effects, and Patient Satisfaction Between Ciprofol Combined with Etomidate Versus Propofol Combined with Etomidate in Painless Gastrointestinal Endoscopy (ChiCTR) - P4 | N=240 | Completed | Sponsor: Wuxi No.2 People's Hospital, Affiliated Central Hospital of Jiangnan University; Wuxi No.2 People's Hospital, Affiliated Central Hospital of Jiangnan

Adverse events • New P4 trial • Pain

KU124 (9,10,10-trioxo-N-(2-phenylphenyl)thioxanthene-3-carboxamide) as a novel inhibitor of TASK-1. (PubMed, Front Pharmacol) - "TASK-1 inhibition is a mechanism of action for some respiratory stimulants, such as doxapram...Our initial success lends validity to our virtual screening methodology and parameters. In this study, we identified a novel TASK-1 inhibitor, KU124, which we verified using an in vitro assay."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Doxapram Administration on Diaphragmatic Excursion in Mechanically Ventilated Patients With Chronic Obstructive Pulmonary Disease Undergoing Spontaneous Breathing Trial (clinicaltrials.gov) - P=N/A | N=35 | Recruiting | Sponsor: Cairo University | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Doxapram Administration on Diaphragmatic Excursion in Mechanically Ventilated Patients With Chronic Obstructive Pulmonary Disease Undergoing Spontaneous Breathing Trial (clinicaltrials.gov) - P=N/A | N=35 | Not yet recruiting | Sponsor: Cairo University

New trial • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Evaluation of the safety of doxapram in premature neonates born before 28 weeks of gestation. (PubMed, Eur J Pediatr) - "In children born before 28 weeks of gestation, doxapram treatment for apnea of prematurity was not associated with the occurrence of gastrointestinal events."

Journal • Retrospective data • Cardiovascular • Gastrointestinal Disorder • Hypertension

Primary respiratory support of extremely preterm neonates in the Netherlands: a national survey. (PubMed, Early Hum Dev) - "The study highlights diverse practices in primary neonatal respiratory support in the Netherlands, with significant variation in NIPPV settings while there is uniformity in CPAP use, underscoring the need for cohesive guidelines and training to standardize care and improve outcomes for extremely preterm neonates."

Journal • Bronchopulmonary Dysplasia • Critical care • Pulmonary Disease • Respiratory Diseases

Caffeine therapy for apnea of prematurity: single center study on dosing practices and perceived effectiveness. (PubMed, Neonatology) - "This study highlights the frequent use of higher caffeine dosages in clinical practice than registered and recommended based on long-term safety data. Despite these high dosages and frequent mini-loads, 28% of patients still required additional treatment with doxapram and/or invasive mechanical ventilation, indicating the need for individualized dosing strategies or alternative therapies."

Journal • Critical care

Study to Investigate the Safety, Tolerability and Pharmacokinetics of QEV-817 Oral Suspension (clinicaltrials.gov) - P1 | N=8 | Not yet recruiting | Sponsor: Quivive Pharma, Inc.

New P1 trial

The effects of doxapram and its potential interactions with K2P channels in experimental model preparations. (PubMed, J Comp Physiol A Neuroethol Sens Neural Behav Phys) - "Since these organisms serve as physiological models for neurobiology and physiology, it would be of interest to further investigate what types of K2P channel are expressed in these tissues. (212 words)."

Journal