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.: PACTR201905684437789 Date of Approval: 27/05/2019
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Bolus or continuous infusion if NTG in acute hypertensive heart failure
Official scientific title Bolus versus Continuous Infusion of Nitroglycerine for treatment of Acute hypertensive heart failure; a randomized clinical study
Brief summary describing the background and objectives of the trial Vasodilators are considered one of the mainstay therapies for acute heart failure (AHF) management. For hypertensive patients with AHF, existing guidelines recommend the use of vasodilators to provide preload and afterload reduction. Although vasodilators improve hemodynamics and symptoms in such patients, they provide no apparent benefit on mortality or hospital readmissions. For hypertensive AHF, nitroglycerin is the vasodilating agent of choice, and when given intravenously (IV), is typically administered as a continuous infusion (dose range, 5-400 μg/min). However, continuous infusions of nitroglycerin have been associated with increased health care costs and hospital length of stay (LOS) leading to questions about their utility in management of AHF. When administered in higher doses by intermittent bolus, nitrates result in greater arterial dilation and more substantial reduction in cardiac afterload leading to favorable changes in central pressure dynamics. Existing trial data on the use of bolus, high dose nitrates suggest that such hemodynamic effects may be a-companied by lower rates of endotracheal intubation, myocardial infarction, and intensive care unit (ICU) admission but the real-world impact of this approach on resource utilization has not been evaluated. Based on prior work by few research groups supporting the use of bolus nitroglycerin therapy, its use has become routine in clinical practice as part of the management of dyspneic, emergency department (ED) patients with hypertensive AHF at their institutions. Accordingly, we designed the present study hypothesizing that administration of nitroglycerin by intermittent bolus would be as effective and safe as continuous infusion when compared in a prospective randomized study. To the best of our knowledge, this is the 1st trial in the literature comparing both strategies for NTG use in patients with hypertensive AHF in a prospective randomized fashion.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) BCINAA
Disease(s) or condition(s) being studied Circulatory System
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Drugs
Anticipated trial start date 01/10/2018
Actual trial start date
Anticipated date of last follow up 01/10/2019
Actual Last follow-up date
Anticipated target sample size (number of participants) 200
Actual target sample size (number of participants)
Recruitment status Recruiting
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 Masking/blinding used Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group NTG in intermittent bolus 10 mg of nitroglycerin is prepared in a 10 mL syringe and given by IV push in increments up to 2 mg every 3 to 5 minutes every 3 to 5 minutes till occurrence of one of the endpoints or clinical improvement. NTG in intermittent bolus fashion 100
Control Group NTG continuous infusion starting dose of 0.3 to 0.5 ug/kg per minute. Titration of the nitroglycerin infusion was allowed in increments of 20 ug per minute every 1 to 3 minutes thereafter at the discretion of the treating emergency physician every 1 to 3 minutes up to occurrence of the defined endpoints or clinical improvement NTG continuous IV infusion 100 Dose Comparison
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. All adult patients presenting to the ED of either study site with hyper-tensive AHF. 2. The diagnosis of hypertensive AHF will be clinical and based on the presence of pulmonary rales, a portable chest radiograph determined by the treating physician to be consistent with pulmonary edema, and 1 or more of the following: a history of heart failure, tach-ypnea (respiratory rate [RR] > 30 breaths/min), significant dyspnea (use of accessory muscles of respiration or obvious air hunger), and significant hypoxia (defined as oxygen saturation [SpO2] < 90% on room air or < 95% on supplemental oxygen) or hypoxemia (partial pressure of arterial oxygen [PaO2] < 50 mm Hg on room air). 3. Ability to obtain written informed consent from the patient or a close family member. Any of the following: 1. Noncardiogenic pulmonary edema, requirement for immediate intubation or cardiopulmonary resuscitation, 2. Inability to obtain informed consent because of alteration in cognition or consciousness or no family or alternative consenting source available 3. Known or suspected pregnancy 4. Acute ST-segment elevation myocardial infarction. 5. Suspected right-sided ventricular ischemia (ST segment depression or new T-wave inversions in leads V1 or V2) 6. Known sensitivity or intolerance to sublingual, transdermal, or intravenous nitroglycerin. 80 and over: 80+ Year,Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 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 23/09/2018 Research Ethics Committee at Benha Faculty Of Medicine in Benha University REC FOMBU
Ethics Committee Address
Street address City Postal code Country
Fareed Nada Benha 13511 Egypt
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome The requirement for endotracheal intubation Within the first 6 hours of treatment
Primary Outcome Primary SAFETY outcome: 1. development of either neurologic complications (defined as presence of any new speech, sensory, or movement deficits de-fined as a transient ischemic attacks or stroke on clinical grounds or by subsequent computed tomography of the brain) or 2. cardiovascular complications, defined as hypotensive epi-sodes requiring intervention or the incidence of acute myocardi-al injury (defined as rise of Troponin level by at least 0.25 ng/ml). within the 1st 24 hours of presentation
Secondary Outcome 1. need for ICU admission, 2. Need for BiPAP 3. total hospital length of stay, 3. worsening of renal dysfunction (as determined by increase in serum creatinine level > 0.5 mg/dL). at 24 or 48 hours
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Benha University Hospital Fareed Nada Benha 13511 Egypt
FUNDING SOURCES
Name of source Street address City Postal code Country
Prof. Mohamed Ebrahim Fareed Nada Benha 13511 Egypt
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Cardiology department at Benha faculty of medicine in Benha University Fareed Nada Benha 13511 Egypt University
COLLABORATORS
Name Street address City Postal code Country
Dr. Mahmoud Shawky Fareed Nada Benha 13511 Egypt
Dr. Mohamed Bendary Kasr EL Eini Cairo 11796 Egypt
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Mohamed Ebrahim mohammed.eita.me@gmail.com +2001007231132 Fareed Nada
City Postal code Country Position/Affiliation
Benha 13511 Egypt Prof of cardiology and Head of Cardiology department at Benha Faculty of medicine in Benha University
Role Name Email Phone Street address
Public Enquiries Ahmed Bendary ahmed.bendari@fmed.bu.edu.eg +2001220778216 Fareed Nada
City Postal code Country Position/Affiliation
Benha 13511 Egypt Lecturer of Cardiology at Benha Faculty of medicine in Benha University
Role Name Email Phone Street address
Scientific Enquiries Ahmed Bendary ahmed.bendari@fmed.bu.edu.eg +200122077816 Fareed Nada
City Postal code Country Position/Affiliation
Benha 13511 Egypt Lecturer of Cardiology at Benha Faculty of medicine in Benha University
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes We are planing to share IPD through the final EXCEL sheet after completion of enrollment. This shall be done through a confidential authorized communication with the responsible correspondents. Study Protocol Six months after publication. Who may and how to request access: Anyone through a confidential and authorized communication (e.g. official emails) with the responsible correspondents. Third party: The Research Ethics Committee at Benha Faculty Of Medicine, Benha University (REC-FOMBU)
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information