Dataset Information

Assessing acute systemic effects of an inhaled drug with serial echocardiography: a placebo-controlled comparison of inhaled and intravenous dihydroergotamine.

ABSTRACT: MAP0004 is an investigational product which delivers dihydroergotamine (DHE) through the lung via a breath-synchronized metered dose inhaler. The objective of this study was to compare the acute effects of orally inhaled and intravenous (IV) DHE to placebo on maximum change and area under the curve for pulmonary arterial systolic pressure (PASP).A randomized, double-blind, placebo-controlled, 3-period, crossover study of 24 health adults. Trial registration NCT01089062. Study assessments included pharmacokinetics, electrocardiograms (ECG), and validated echocardiographic (Doppler)-derived measures of PASP by echocardiogram. The primary endpoint was the absolute change in calculated PASP using area under the curve, 0 to 2 hours (AUC(0-2h)).The change in PASP with IV DHE was significantly different than MAP0004 and placebo (AUC(0-2h)2857, 2624, and 2453 mmHg*min, respectively). After a second dose of MAP0004, AUC(0-4h) remained lower with MAP0004 than with a single dose of IV DHE. Adverse events were more common with IV DHE than with MAP0004 or placebo. None of the treatments produced clinically significant changes in PASP or other cardiac parameters. Changes in PASP were significantly smaller with MAP0004 compared with IV DHE.These results indicate the effects 1 mg of orally inhaled DHE on the cardiovascular system are less than with 1 mg of IV DHE, and that serial echocardiography can be a useful noninvasive means of assessing acute systemic effects.

SUBMITTER: Noveck RJ

PROVIDER: S-EPMC3728267 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Assessing acute systemic effects of an inhaled drug with serial echocardiography: a placebo-controlled comparison of inhaled and intravenous dihydroergotamine.

Noveck Robert J RJ Douglas Pamela S PS Chow Shein-Chung SC Mangum Barry B Kori Shashidhar S Kellerman Donald J DJ

Drug design, development and therapy 20130724

<h4>Objective</h4>MAP0004 is an investigational product which delivers dihydroergotamine (DHE) through the lung via a breath-synchronized metered dose inhaler. The objective of this study was to compare the acute effects of orally inhaled and intravenous (IV) DHE to placebo on maximum change and area under the curve for pulmonary arterial systolic pressure (PASP).<h4>Research design and methods</h4>A randomized, double-blind, placebo-controlled, 3-period, crossover study of 24 health adults. Tri ...[more]

PMID: 23926420

Similar Datasets

Project description:Septic shock is the leading cause of cardiovascular failure in the intensive care unit (ICU). Cardiac output is a primary component of global oxygen delivery to organs and a sensitive parameter of cardiovascular failure. Any mismatch between oxygen delivery and rapidly varying metabolic demand may result in tissue dysoxia, hence organ dysfunction. Since the intricate alterations of both vascular and cardiac function may rapidly and widely change over time, cardiac output should be measured repeatedly to characterize the type of shock, select the appropriate therapeutic intervention, and evaluate patient's response to therapy. Among the numerous techniques commercially available for measuring cardiac output, transpulmonary thermodilution (TPT) provides a continuous monitoring with external calibration capability, whereas critical care echocardiography (CCE) offers serial hemodynamic assessments. CCE allows early identification of potential sources of inaccuracy of TPT, including right ventricular failure, severe tricuspid or left-sided regurgitations, intracardiac shunt, very low flow states, or dynamic left ventricular outflow tract obstruction. In addition, CCE has the unique advantage of depicting the distinct components generating left ventricular stroke volume (large cavity size vs. preserved contractility), providing information on left ventricular diastolic properties and filling pressures, and assessing pulmonary artery pressure. Since inotropes may have deleterious effects if misused, their initiation should be based on the documentation of a cardiac dysfunction at the origin of the low flow state by CCE. Experts widely advocate using CCE as a first-line modality to initially evaluate the hemodynamic profile associated with shock, as opposed to more invasive techniques. Repeated assessments of both the efficacy (amplitude of the positive response) and tolerance (absence of side-effect) of therapeutic interventions are required to best guide patient management. Overall, TPT allowing continuous tracking of cardiac output variations and CCE appear complementary rather than mutually exclusive in patients with septic shock who require advanced hemodynamic monitoring.

Project description:BackgroundDengue virus infection (DVI) is a major health problem in many parts of the world. Its manifestations range from asymptomatic infections to severe disease. Although cardiac involvement has been reported in DVI, its incidence has not yet been well established.MethodsFrom July 2016 to January 2018, patients hospitalized at the Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Thailand, with dengue virus infection confirmed by positive NS1 or positive dengue immunoglobulin M findings, participated in the study. We characterized the incidence and change in cardiac function by serial echocardiography and levels of troponin-T and creatine kinase-myocardial band (CK-MB) on the day of admission, the day of defervescence, the first day of hypotension (if any), and at 2 week follow-up.ResultsOf the 81 patients evaluated, 6 (7.41%) exhibited elevated biomarker levels. There was no difference in clinical presentation amongst dengue fever, dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS), except for the amount of bleeding. Cardiac involvement was found in 22.2% of patients: 3 (3.70%) had left ventricular systolic dysfunction, 3 (3.70%) had transient diastolic dysfunction, 6 (7.41%) had increased levels of at least one cardiac biomarker (troponin-T or CK-MB), and 6 (7.41%) had small pericardial effusion. Myocarditis was suspected in only two patients (with DHF); thus, myocarditis was uncommon in patients with dengue virus infection. Three patients developed DSS during admission and were transferred to the intensive care unit.ConclusionCardiac involvement in adults with dengue infection was common, ranging from elevated cardiac biomarker to myocarditis. Abnormalities in cardiac function had resolved spontaneously by the day of follow-up, without specific treatment. We found that DHF was a significant risk factor for cardiac involvement. Echocardiography is the investigation of choice for evaluating the haemodynamic status of patients with DVI, especially in severe dengue.

Dataset Information

Assessing acute systemic effects of an inhaled drug with serial echocardiography: a placebo-controlled comparison of inhaled and intravenous dihydroergotamine.

Publications

Assessing acute systemic effects of an inhaled drug with serial echocardiography: a placebo-controlled comparison of inhaled and intravenous dihydroergotamine.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets