Balti ii trial

Randomisation Once written, informed consent has been obtained for the patient to participate in the trial the patient will be randomised to treatment with salbutamol or placebo. Trial Treatments 2. Test Treatment Active ingredient: Salbutamol Sulphate. Excipient: Sodium chloride, sodium hydroxide and Water for Injection. Pharmaceutical Form: Sterile injection. Manufacturer: Hameln Pharmaceuticals Ltd. Calculation of Infusion Rate Salbutamol and placebo infusions will be administered through a dedicated intravenous line at a rate of 0.

Alteration of Infusion Rate Sinus tachycardia or arrhythmias are known side effects of intravenous salbutamol administration. Infusion Termination Criteria Termination of the infusion is defined as discontinuation of the trial drug infusion without intention to restart the infusion at a later time. Trial drug infusion will be terminated in the following circumstances: Death. Development of a significant lactic acidosis, which in the opinion of the treating clinician is attributable to infusion of the trial drug.

Decision by the attending clinician that the infusion should be discontinued on safety grounds. Treatment Compliance Treatment will be administered by site personnel with relevant training and experience at the hospital. Drug Accountability Hospital pharmacies will be responsible for recording trial drug packs dispensed to the ICU.

Acute Bronchospasm In the event of acute bronchospasm, where the clinician feels that a nebulised bronchodilator is required, nebulised ipratropium bromide may be given. Ventilatory Management There are no specific guidelines for ventilatory management. Blinding and Procedures for Unblinding Patients As a placebo controlled, double-blind trial, patients, clinicians and investigators will be blinded to each patient's allocation.

Post Infusion Follow-up Any patients who remain in the Intensive Care Unit or High Dependency Unit for more that seven days post randomisation the end of the expected drug infusion period , will continue to be monitored on daily basis until discharged to a ward.

Adverse Event Management 2. Definitions 2. Adverse Events An adverse event is defined as any untoward medical occurrence in a patient administered a medicinal product and which does not necessarily have a causal relationship with the treatment.

The following are expected adverse events and will be recorded on the CRF: Termination of trial drug due to tachycardia. Requires medical intervention to prevent one of the above, or is otherwise considered medically significant. Side effects of salbutamol sufficiently severe to be fatal or immediately life-threatening.

End of Trial The trial will end when patients have been recruited and completed twelve month follow-up. The trial will be stopped prematurely if: Mandated by the Ethics Committee. Data Management 3. Training Issues To ensure accurate, complete and reliable data, the Trial Co-ordinating Centre will do the following: Provide instructional material to the trial site s. Provide an Initiation training session to instruct the Investigators and trial nurses.

This session will give instructions on the protocol, the completion of Case Report Forms and trial procedures. Data Collection and Management All data for an individual patient will be collected by each Principal Investigator or their delegated nominees and recorded in the CRF. Follow-up at Six and Twelve months All survivors will be followed up at six and twelve months after randomisation by postal questionnaire.

Data Storage All essential documentation and trial records will be stored by WMSCTU in conformance with the applicable regulatory requirements and access to stored information will be restricted to authorised personnel. Archiving Trial documentation and data will be archived for at least five years after completion of the trial.

Data Analysis 4. Sample size calculation The estimated sample size is patients in each arm. Statistical Analysis 4. General Analysis All analyses will be by intention to treat i. Frequency of Analyses Interim analyses will be conducted every 12 months during the period of recruitment, or more frequently if requested by the DMEC.

Economic Evaluation 4. Economic Analyses Two economic analyses will be undertaken: 1. Publication of Results The success of the trial depends on the collaboration of doctors, nurses and researchers from across the UK. Trial Organisation 5. The Steering Committee, in the development of this protocol and throughout the trial will take responsibility for: Major decisions such as a need to change the protocol for any reason.

The trial is managed by a multi-disciplinary team page 3. In addition the trial office team will: Distribute the standardised data collection forms to collaborators. Indemnity NHS indemnity covers NHS staff, medical academic staff with honorary contracts, and those conducting the trial. Monitoring and Safety Procedures 5. Early termination of the trial in response to safety issues will be addressed via the DMEC. Monitoring of Trial Conduct The Trial Manager and Recruitment Facilitators will undertake site visits to ensure that the trial protocol is adhered to and that necessary paperwork CRF's, Patient Consent are being completed appropriately.

Ethics and Regulatory Approval The trial will be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki. Reference List 1. Acute respiratory distress in adults. Lancet ;— Adult respiratory distress syndrome: risk with common predispositions.

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Structural alterations of lung parenchyma in the adult respiratory distress syndrome. Clin Chest Med ;— Corrin B. Diffuse Alveolar Damage. Acute Respiratory Distress Syndrome. Bellingan GJ. Thorax ;—6. Tomashefski JF, Jr. Pulmonary pathology of acute respiratory distress syndrome. Treatment of adult respiratory distress syndrome: plea for rescue therapy of the alveolar epithelium.

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Bench-to-bedside review: beta2-Agonists and the acute respiratory distress syndrome. Crit Care ;— Clinically relevant concentrations of beta2-adrenergic agonists stimulate maximal cyclic adenosine monophosphate-dependent airspace fluid clearance and decrease pulmonary edema in experimental acid-induced lung injury. Crit Care Med ;—6. Betaadrenoceptor agonists as inhibitors of lung vascular permeability to radiolabelled transferrin in the adult respiratory distress syndrome in man.

Eur J Nucl Med ;—4. Perkins GD. Thorax ii1. Do Beta agonists promote epithelial repair? Thorax 60, ii Effect of bronchodilators on lung mechanics in the acute respiratory distress syndrome ARDS. Chest ;— Effects of nebulized salbutamol on respiratory mechanics in adult respiratory distress syndrome. Respiratory mechanics and bronchodilator responsiveness in patients with the adult respiratory distress syndrome. Crit Care Med ;— Inhaled beta-2 agonist salbutamol and acute lung injury: an association with improvement in acute lung injury.

Crit Care ;R Alveolar fluid clearance is impaired in the majority of patients with acute lung injury and the acute respiratory distress syndrome. The American-European Consensus Conference on ARDS, part 2: Ventilatory, pharmacologic, supportive therapy, study design strategies, and issues related to recovery and remodeling.

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Am J Obstet Gynecol ;—6. Harris L. Comparison of the effect on blood gases, ventilation, and perfusion of isoproterenol-phenylephrine and salbutamol aerosols in chronic bronchitis with asthma. J Allergy Clin Immunol ;— Metabolic effects of salbutamol: comparison of aerosol and intravenous administration.

British Medical Journal ;— Beta-mimetics in preterm labour: an overview of the randomized controlled trials. Br J Obstet Gynaecol ;— Etiology and prevention of pulmonary complications following beta-mimetic mediated tocolysis. The renin-angiotensin-aldosterone system, antidiuretic hormone levels and water balance under tocolytic therapy with Fenoterol and Verapamil.

Int J Gynaecol Obstet ;—5. Urinary excretion, osmolarity and electrolytes after bolus-injection of fenoterol in female rabbits. Gynecol Obstet Invest ;— Transient lactic acidosis as a side effect of inhaled salbutamol. Chest ;—6. The effect of dopamine and adrenaline infusion on acid-base balance and systemic haemodynamics in severe infection. Statistical evaluation of ventilator-free days as an efficacy measure in clinical trials of treatments for acute respiratory distress syndrome. Crit Care Med ;—7.

ARDSNet definitions and recommendations. Ref Type: Report. This work was produced by Gates et al. This issue may be freely reproduced for the purposes of private research and study and extracts or indeed, the full report may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising.

Appendix 2, Final study protocol. In this Page. Other titles in this collection. Health Technology Assessment. Related information. Recent Activity. A previous randomised controlled Phase II trial suggested that an intravenous i. To evaluate salbutamol's clinical effectiveness and its cost-effectiveness in subgroups of patients. Design: A multicentre, randomised, placebo-controlled trial. Results: Forty-six ICUs recruited patients to the trial.

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