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: www.pactr.org
Trial no.: PACTR202007606032743 Date of Approval: 07/07/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Nebulized heparin in patients with mainly moderate coronavirus disease 2019: Randomized controlled trial. COVID-19
Official scientific title Nebulized heparin in patients with mainly moderate coronavirus disease 2019: Randomized controlled trial. COVID-19
Brief summary describing the background and objectives of the trial Introduction The COVID-19 pandemic has quickly spread throughout the world and threatens to overwhelm our critical care bed supply in Egypt in the upcoming weeks. Salvage use of therapeutics targeted at attenuating acute respiratory distress syndrome (ARDS) as a sequalae COVID-19-related mortality is of high interest (1). There is growing evidence that lethal COVID-19 ARDS is associated with disseminated intravascular fibrin deposition and in the alveolar sac (2). Current therapeutic strategy to decrease ARDS associated mortality is to utilize protective mechanical ventilation in combination with low tidal volume. However, morbidity and mortality remain high, both exceeding 40% (3). The need for new specific pharmacological therapies has carried to examine the role of altered coagulation and fibrinolysis in the pathogenesis of ARDS. Nebulization of heparin may offer benefits over systemic administration because nebulization enhances delivery to the bronchial tree and the alveolar sacs and reduces the potential for systemic bleeding associated with intravenous administration. Furthermore, nebulized heparin has been shown to reduce levels of coagulation activation in the lungs both in animal studies and in patients with ALI (4). As Heparin prevents further fibrin deposition but ineffective in the removal of pre-existing fibrin plug, so early use of heparin during the course of the disease may limit the complications of ARDS and/or reduce the burden on ventilatory support in intensive care units.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied COVID 19
Purpose of the trial Treatment: Drugs
Anticipated trial start date 15/06/2020
Actual trial start date
Anticipated date of last follow up 31/07/2020
Actual Last follow-up date
Anticipated target sample size (number of participants) 100
Actual target sample size (number of participants) 100
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
Factorial: participants randomly allocated to either no, one, some or all interventions simultaneously Randomised Simple randomization using by using procedures such as coin-tossing or dice-rolling Sealed opaque envelopes Masking/blinding used Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group standard of care group 24 hour after randomization and will continue for one week. patients will be managed with standard of care aligned with the indications from the updated national clinical practice guidelines of ministry of health in Egypt 50 Active-Treatment of Control Group
Experimental Group Standard of care plus nebulized heparin patients will be managed with the same standard care plus nebulized heparin (1,000 IU/kg) every 6 hours started 24 hour after randomization and will continue for one week 50
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Age:18-60 years old, recently diagnosed (within 24 h) and moderate symptoms of the disease ongoing SARS-CoV-2 infection confirmed in upper or lower respiratory tract specimens with real time reverse transcriptase polymerase chain reaction (RT-PCR), willingness to participate. Pneumonia on computed tomography of the chest will not be mandatory for inclusion. age below 18 years, severe conditions including malignancies, heart, liver, or kidney disease, poorly controlled metabolic diseases, pregnancy or lactation, severe hepatic impairment (e.g. Child Pugh grade C, alanine aminotransferase more than fivefold the upper limit), severe renal impairment (estimated glomerular filtration rate ≤30 mL/min/1.73 m2) , receipt of continuous renal replacement therapy, hemodialysis, peritoneal dialysis, allergy to heparin (including any history of heparin-induced thrombocytopenia), pulmonary hemorrhage in the previous 3 months, uncontrolled bleeding or a significant bleeding disorder, an intracranial hemorrhage in the past 12 months and patients with mild and severe COVID-19 will be excluded. Adult: 19 Year-44 Year,Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 60 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 21/05/2020 Ethics committee Faculty of medicine Alexandria University
Ethics Committee Address
Street address City Postal code Country
7 Champollion Street, El Messalah, Alexandria, Egypt. Alexandria 21568 Egypt
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome The primary outcome will be the average daily ratio of partial pressure of oxygen to FiO2 (PaO2/FiO2) while the patient on room air for 7 days. daily for 7 days
Secondary Outcome Secondary outcomes will be Levels in pulmonary lavage fluid of fibrin degradation products (FDPs) as a marker of coagulation activation, measured at baseline and on study Days 3 and 7, it will be measured through mini bronchoalveolar lavage (BAL) fluid samples as patients remained non ventilated. Daily APPT levels in seconds and Platelet count (×109/L) will be recorded to assess the systemic effects of nebulized heparin. Incidence of serious respiratory events that need further respiratory support from randomization to 14 days. FDPs will be measured at baseline and on study Days 3 and 7, APPT will be measured daily, serious respiratory event will be assessed from start of trial till 14 days after randomization
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
15 May hospital 15th of May City, 3rd Mogawra , Cairo 1111 Egypt
FUNDING SOURCES
Name of source Street address City Postal code Country
Tarek ismail 152 tiba st. sporting alexandria Egypt
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Dr Tarek Ismail 152 tiba st. sporting alexandria 21617 Egypt Individual
Secondary Sponsor Dr Rabab S. Mahrous Faculty of Medicine el sultan Hussein st., El shatby alexandria Egypt Individual
COLLABORATORS
Name Street address City Postal code Country
Dr Rabab Mahrous Anesthesia Department, El Sultan Hussein El shatby, Faculty of Medicine, Alexandria University Alexandria Egypt
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Tarek Ismail drtarek.anesth@gmail.com 00201001467166 152 tiba st. sporting
City Postal code Country Position/Affiliation
alexandria 21617 Egypt Lecturer of Anesthesia and Surgical Intensive Care Helwan University Egyp
Role Name Email Phone Street address
Public Enquiries Amal Mohamed amalasaic@gmail.com +201281560053 Faculty of Medicine, El Sultan Hussein St. Anesthesia Department
City Postal code Country Position/Affiliation
Alexandria Egypt Secretary of Research and opinion in Anesthesia and intensive care Journal
Role Name Email Phone Street address
Scientific Enquiries Tarek Salem tareksalem00@gmail.com 00201112277417 Al Gamaa, Al Masaken Al Iqtisadeyah, Qism Helwan
City Postal code Country Position/Affiliation
Cairo Egypt Vice dean of graduate studies and Research
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes excel sheets with patient data Statistical Analysis Plan,Study Protocol additional documents will be available within 12 months after completion of the study. open access to IPD to reviewers. Data will be send directly by email upon request.
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
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Public title 02/07/2020 edit Nebulized heparin in patients with mainly moderate coronavirus disease 2019: Randomized controlled trial Nebulized heparin in patients with mainly moderate coronavirus disease 2019: Randomized controlled trial. COVID-19
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Official scientific title 02/07/2020 edit Nebulized heparin in patients with mainly moderate coronavirus disease 2019: Randomized controlled trial Nebulized heparin in patients with mainly moderate coronavirus disease 2019: Randomized controlled trial. COVID-19
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 02/07/2020 edit Experimental Group, Standard of care plus, , patients will be managed with the same standard care plus nebulized heparin (1,000 IU/kg) , every 6 hours started 24 hour after randomization and will continue for one week, 50, Experimental Group, Standard of care plus nebulized heparin, , patients will be managed with the same standard care plus nebulized heparin (1,000 IU/kg) , every 6 hours started 24 hour after randomization and will continue for one week, 50,
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 04/07/2020 English version of the approval document showing the name of the institution, as well as the date of approval. TRUE, Ethics committee Faculty of medicine Alexandria University, 7 Champollion Street, El Messalah, Alexandria, Egypt., Alexandria, 21568, Egypt, , 21 May 2020, 00201287740750, ecthics.comm@alexmed.edu.eg, 12158_11456_4737.pdf TRUE, Ethics committee Faculty of medicine Alexandria University, 7 Champollion Street, El Messalah, Alexandria, Egypt., Alexandria, 21568, Egypt, , 21 May 2020, 00201287740750, ecthics.comm@alexmed.edu.eg, 12158_11456_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Funding Source FundingSources List 04/07/2020 to identify that the study is self-funded Tarek ismail, 152 tiba st. sporting, alexandria, , Egypt, Self Funded,
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 04/07/2020 English version of the approval document showing the name of the institution, as well as the date of approval. TRUE, Ethics committee Faculty of medicine Alexandria University, 7 Champollion Street, El Messalah, Alexandria, Egypt., Alexandria, 21568, Egypt, , 21 May 2020, 00201287740750, ecthics.comm@alexmed.edu.eg, 12158_11456_4737.pdf TRUE, Ethics committee Faculty of medicine Alexandria University, 7 Champollion Street, El Messalah, Alexandria, Egypt., Alexandria, 21568, Egypt, , 21 May 2020, 00201287740750, ecthics.comm@alexmed.edu.eg, 12158_11456_4737.pdf