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.: PACTR202306656398595 Date of Approval: 12/06/2023
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title Chest ultrasonographic evaluation after intrapleural Alteplase versus Streptokinase injection in Children with Empyema
Official scientific title Chest ultrasonographic evaluation after intrapleural Alteplase versus Streptokinase injection in Children with Empyema
Brief summary describing the background and objectives of the trial Empyema is the state in which purulent fluid is present in the pleural space. If pleural effusion is purulent, a diagnosis of empyema is given even if a microbial test is not positive (1). CPPE (complicated parapneumonic effusion) was defined as nonpurulent effusions in a patient with clinical evidence of infection such as fever and/or elevated blood leukocyte count and/or elevated CRP (C-reactive protein), with pleural fluid pH<7.2 (measured by blood-gas analyzer), pleural fluid glucose,60 mg/dl, or pleural-fluid lactate dehydrogenase (LDH).1,000 IU/L (2). Parapneumonic effusion or pleural empyema (PPE/PE) is a frequent complication of community-acquired pneumonia (CAP) in children. Different management approach exist for this condition(3). Parapneumonic pleural effusions may occur in 3657% of patients with pneumonia and about 1520% of this accumulated fluid becomes infected resulting in empyema (4). Drainage of the collection in early stage by intercostal tube with administration of proper antibiotics according to the culture and sensitivity is considered the cornerstone of treatment(5). Clinical guidelines recommend that empyema is to be treated with chest tube insertion and intrapleural fibrinolytics (6). Variety of fibrinolytic agents such as streptokinase, alteplase and urokinase had been administered selectively and safely in the management of pleural effusion and empyema (7). Intrapleural fibrinolytic therapy was often used in pediatric empyema, despite limitations with current evidence (8). The aim of this study is to compare the benefit of intrapleural injection of tissue plasminogen activator versus streptokinase in children with CPPE or empyema in length of stay in hospital following chest tube and need for additional surgical pleural drainage procedures. 1. Kanai E, Matsutani N. Management of empyema: A comprehensive review. Curr Chall Thorac Surg. 2020;2:38. 2. Kheir F, Thakore S, Mehta H, Jantz M, Parikh M, Chee A, et al. Intrapleural fibrinolytic
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Paediatrics,Respiratory
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Drugs
Anticipated trial start date 30/03/2023
Actual trial start date 30/04/2023
Anticipated date of last follow up 29/03/2025
Actual Last follow-up date 30/04/2025
Anticipated target sample size (number of participants) 75
Actual target sample size (number of participants) 75
Recruitment status Active, not 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 Central randomisation by phone/fax Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group intrapleural Alteplase or Streptokinase injection in Children with Empyema or conservative approach (1)Group 1 intrapleural tPA injection, 2-4 mg (dissolved in 10 to 40 mL of normal saline) every 24 hours or (2) Group 2 will receive intrapleural streptokinase injection at dose 15,000 unit/kg/dose in 100 ml (3)Group 3 will be managed with conservative approach through intercostal tube application. intrapleural tPA injection for 3 doses every 24 hours intrapleural streptokinase injection for maximum duration of 14 days but the patient may not require the whole course if there is a clinical resolution at an earlier stage. conservative approach through intercostal tube application and removed when drained fluid less than 1 ml/kg/day. Participants will be randomized to either (1)Group 1 will receive intrapleural tPA injection, 2-4 mg (dissolved in 10 to 40 mL of normal saline). The chest tube will be clamped for 1 hour and then allowed to drain underwater seal. The first dose will be typically given within 1 hour of chest tube insertion for 3 doses every 24 hours according to clinical and radiological response (chest ultrasonography) or (2) Group 2 will receive intrapleural streptokinase injection at dose 15,000 unit/kg/dose in 100 ml of normal saline within 24 hours of chest tube insertion which will be infused within one hour and clamped for four hours for maximum duration of 14 days but the patient may not require the whole course if there is a clinical resolution at an earlier stage. (3)Group 3 will be managed with conservative approach through intercostal tube application. 75 Placebo
Experimental Group intrapleural streptokinase injection 15,000 unit/kg/dose in 100 ml of normal saline maximum duration of 14 days but the patient may not require the whole course if there is a clinical resolution at an earlier stage. Group 2 will receive intrapleural streptokinase injection at dose 15,000 unit/kg/dose in 100 ml of normal saline within 24 hours of chest tube insertion which will be infused within one hour and clamped for four hours for maximum duration of 14 days but the patient may not require the whole course if there is a clinical resolution at an earlier stage. 25
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Age: from1 month to18 years. Gender: both sexes will be included in the study. Empyema or CPPE along with evidence of septated pleural effusion on chest ultrasonography. All patients will undergo chest tube insertion along with intravenous antibiotics. Age below 1 month. Patients with chronic empyema which is characterized by thickened visceral and parietal peels which hamper the ability of affected lung to re-expand and required definitive surgical intervention. Patients with bleeding tendency, recent trauma, recent operation and on anticoagulation. Children with pleural empyema from tuberculosis or malignancy. Children with allergy to tPA or streptokinase. Children with minimal parapneumonic effusion that do not require chest tube insertion. Presence of bronchopleural fistula or pyopneumothorax. Adolescent: 13 Year-18 Year,Child: 6 Year-12 Year,Infant: 13 Month(s)-24 Month(s),Preschool Child: 2 Year-5 Year 1 Month(s) 18 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 20/05/2023 Institutional review board faculty of medicine Assuit university
Ethics Committee Address
Street address City Postal code Country
Assuit Assuit 71515 Egypt
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Primary outcome is assessment of the benefit and possible complications of intrapleural injection of tissue plasminogen activator and streptokinase in children with CPPE or empyema. daily chest ultrasonography to measure the amount of intrapleural fluid and detect intrapleural adhesions according to their mobility into freely mobile septa, fixed, or mixed. Chest ultrasonography
Secondary Outcome To compare between intrapleural injection of tissue plasminogen activator versus streptokinase in children with CPPE or empyema in reducing the need of further surgical intervention. Chest ultrasonography will be done to all patients upon clinic follow-up to detect if any additional pleural interventions will be necessary.
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Assiut University Children Hospital. Assuit Assuit Egypt
FUNDING SOURCES
Name of source Street address City Postal code Country
Principal investigator Assuit Assuit Egypt
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Assiut University Children Hospital. Assuit University Hospital Assuit Egypt Hospital
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Public Enquiries Mohamed Sayed mohamed000@aun.edu.eg 01153999115 Assuit
City Postal code Country Position/Affiliation
Assuit Egypt Lecturer
Role Name Email Phone Street address
Scientific Enquiries Yasser Farouk yasser.rezk@med.au.edu.eg 01111168123 Assuit
City Postal code Country Position/Affiliation
Assuit Egypt Assistant Professor
Role Name Email Phone Street address
Principal Investigator Asmaa Tawfik asmaammt@gmail.com 01155096915 Assuit
City Postal code Country Position/Affiliation
Assuit Egypt Assistant lecturer
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Data obtained through this study may be provided to qualified researchers with academic interest in empyma in children. Data or samples shared will be coded, with no PHI included. Approval of the request and execution of all applicable agreements (i.e. a material transfer agreement) are prerequisites to the sharing of data with the requesting party. Informed Consent Form,Statistical Analysis Plan,Study Protocol Data requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis. Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA).
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