Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202404531355476 Date of Approval: 26/04/2024
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title Effect Of Intravenous Metoprolol Tartrate On Mortality In Patients With Septic Shock Due To Ventilator-Associated Pneumonia
Official scientific title Effect Of Intravenous Metoprolol Tartrate On Mortality In Patients With Septic Shock Due To Ventilator-Associated Pneumonia
Brief summary describing the background and objectives of the trial Background: Septic shock, characterized by systemic inflammation and cardiovascular dysfunction, remains a leading cause of mortality in critically ill patients, particularly those with ventilator-associated pneumonia (VAP). Despite advances in management, mortality rates remain high, emphasizing the need for novel therapeutic approaches to improve outcomes. Beta-blockers, such as metoprolol, have been proposed as adjunctive therapy in septic shock due to their potential to modulate excessive sympathetic activity and reduce heart rate, thereby improving myocardial oxygen balance and organ perfusion. Objectives: The current randomized controlled trial aimed to evaluate the efficacy and safety of intravenous metoprolol administration in patients with septic shock secondary to VAP. The primary objective was to assess whether metoprolol could effectively lower heart rate below a predetermined threshold and evaluate its subsequent impact on systemic hemodynamics, organ function, adverse events, and 28-day mortality. Secondary objectives included examining the effects of metoprolol on the duration of mechanical ventilation, length of ICU stay, and hospital stay. The study sought to compare outcomes between patients receiving metoprolol and those receiving standard care for septic shock. This trial aimed to address the gap in current management strategies for septic shock by investigating the potential role of beta-blockade in improving hemodynamic stability and clinical outcomes in this high-risk patient population.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Circulatory System,Respiratory
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Drugs
Anticipated trial start date 01/10/2023
Actual trial start date 01/10/2023
Anticipated date of last follow up 29/02/2024
Actual Last follow-up date
Anticipated target sample size (number of participants) 100
Actual target sample size (number of participants)
Recruitment status Completed
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using a randomization table created by a computer software program Sealed opaque envelopes Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group intravenous metoprolol tartrate The dose of Metoprolol administered intravenously ranged from 2.5 to 5 mg of metoprolol tartrate every 2 to 5 minutes, with a maximum total dose of 15 mg given over 10 to 15 minutes to achieve a target heart rate of 70-80 beats per minute. Additional doses were administered as needed to maintain the target heart rate throughout the resuscitation period and until the resolution of the shock state. The duration of administration for Metoprolol was over a period of 2 to 10 days, till reaching and maintaining a target heart rate of 70-80/min. Metoprolol was administered to patients in the experimental group with a dose ranging from 2.5 to 5 mg of metoprolol tartrate every 2 to 5 minutes. The total dose administered did not exceed 15 mg and was given over a period of 10 to 15 minutes to achieve a target heart rate of 70-80 beats per minute. Additional doses were given as necessary to maintain the target heart rate throughout the resuscitation period and until the resolution of the shock state. Discontinuation criteria included MAP <65 mmHg, heart rate deviation from target, or severe arrhythmias. 50
Control Group routine management of septic shock according to surviving sepsis campaign without giving Metoprolol No additional drugs were given. No additional drugs were given. The patient received care as long as needed till resolution of shock state The intervention in the control group involved providing routine management for septic shock without administering Metoprolol. This would typically include standard care protocols such as fluid resuscitation, vasopressor therapy as needed to maintain hemodynamic stability, antibiotic administration, lung protective ventilation strategies, and other supportive measures recommended by clinical guidelines. The specific details of the intervention would align with the standard practices followed in the critical care department at Alexandria Main University Hospital where the trial was conducted. 50 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Adult patients (≥ 18 years old). Diagnosed with septic shock secondary to ventilator-associated pneumonia (VAP). Presenting with sinus tachycardia. Hemodynamically stabilized with mean arterial pressure (MAP) > 65 mmHg. Willingness to participate and provide informed consent. Contraindications to beta-blockers. History of heart failure. Previous use of beta-blockers prior to septic shock. Development of complications from beta-blocker administration. Adult: 19 Year-44 Year 18 Year(s) 80 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 18/11/2021 Ethics committee faculty of medicine alexandria university
Ethics Committee Address
Street address City Postal code Country
17 champlion street, El Messalah, Alexandria, Egypt Alexandria 00203 Egypt
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome 28-day mortality 28-day
Secondary Outcome Mechanical ventilation days Every day from the time of enrollment until the respective endpoints are reached.
Secondary Outcome Days of ICU stay Every day from the time of enrollment until the respective endpoints are reached.
Secondary Outcome Days of hospital saty Every day from the time of enrollment until the respective endpoints are reached.
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Alexandria Main university hospita 17 Champlion Street, Elmessalah, Alexandria, Egypt. Alexandria 21563 Egypt
FUNDING SOURCES
Name of source Street address City Postal code Country
Alexandria Main university hospital 17 champoilion street, El Messalah Alexandria 21563 Egypt
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Secondary Sponsor Safaa Fahmy Mohey Eldein Algeish street Desouk 33611 Egypt Individual
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Sherouk Rafik Hamad sheroukrafik@gmail.com 00201013459188 Elgeish street
City Postal code Country Position/Affiliation
Desouk 33611 Egypt Critical care resident
Role Name Email Phone Street address
Scientific Enquiries Akram Muhammad Fayed Amfayed@gmail.com 002035934095 55 port-said street, Camp Shizar
City Postal code Country Position/Affiliation
Alexandria Egypt Professor of Critical Care Medicine
Role Name Email Phone Street address
Public Enquiries Haytham Saber Meligy Hmeligy1@gmail.com 002035552030 Mohamed Naguib street, sidi beshr bahry
City Postal code Country Position/Affiliation
Alexandria Egypt Lecturer of Critical Care Medicine
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes IPD from this clinical trial encompass comprehensive datasets collected from each participant throughout the study period. These datasets include detailed information on participant demographics, medical history, baseline characteristics, treatment interventions, clinical outcomes, laboratory results, and adverse events. All data are anonymized to protect participant confidentiality and comply with data protection regulations. Study Protocol The IPD-sharing time frame will commence once the primary findings have been disseminated through publication or another recognized channel, approxiametly within one year and it will extend indefinitely thereafter IPD from this clinical trial is available to qualified researchers and investigators, who may submit requests for access to the Principal Investigator. Requests should include a detailed description of the proposed research objectives and analytical plan, along with documentation of ethical approval and a commitment to adhere to data protection regulations. Access criteria include considerations of scientific merit, feasibility, and ethical compliance, with decisions based on the fulfillment of these criteria. Permitted analyses encompass primary and secondary research objectives, as well as meta-analyses, promoting scientific collaboration and transparency while upholding participant confidentiality and data integrity. Contact information for inquiries regarding IPD access and the access criteria is provided through the Principal Investigator of the trial.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
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Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information