South African National Clinical Trials Registry
South African Medical Research Council, Cochrane South Africa
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: sactradmin@mrc.ac.za Website: sanctr.samrc.ac.za
Trial no.: DOH-27-032023-8464 Date of Approval: 02/03/2023
Trial Status: Approved
TRIAL DESCRIPTION
Public title APC-AF-CLN-004
Official scientific title A South African multicenter, phase 2, non-blinded, randomized controlled trial to determine if aerosolized surfactant plus continuous positive airway pressure (CPAP) compared to CPAP alone can improve the course of infants with respiratory distress syndrome (RDS) by decreasing their need for intratracheal bolus surfactant in the first 72 hours of age.
Brief summary describing the background and objectives of the trial A South African multicenter, phase 2, non-blinded, randomized controlled trial to determine if aerosolized surfactant plus continuous positive airway pressure (CPAP) compared to CPAP alone can improve the course of infants with respiratory distress syndrome (RDS) by decreasing their need for intratracheal bolus surfactant in the first 72 hours of age.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Respiratory
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Supportive care
Anticipated trial start date 16/01/2023
Actual trial start date
Anticipated date of last follow up 31/12/2026
Actual Last follow-up date
Anticipated target sample size (number of participants) 332
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
APC-AF-CLN-004 Aerogen Pharma Ltd
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 Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group SFR1 1 Surfactant 216mg/k per dose 2 - 32 hours of age As soon as possible following randomization to the Intervention group, infants will receive one dose of aerosolized SF-RI 1 surfactant of 216 mg/k per dose if they have: a persistent FiO2 of 0.25 – 0.35 on nCPAP at 5-7cmH2O0 to maintain peripheral oxygen saturation of 90 -95%. FiO2 requirement needs to be sustained for at least 15 minutes. The dose of SF-RI 1 will be calculated by the designated study staff member. The estimated time to deliver a single dose of SF-RI 1 by aerosolization is: 1000 g: 60 - 90 minutes 1500 g: 90 – 120 minutes 2000 g: 120- 180 minutes . Infants randomized to the Intervention group may receive one additional dose of aerosolized SF-RI 1 surfactant of 216 mg/kg per dose (for a total of two doses) if the following re-dosing criteria are met: 30 minutes have elapsed since the end of the first dose and an ongoing and persistent FiO2 of 0.30 – 0.40 on nCPAP at 5-7 cmH2O to maintain peripheral oxygen saturation of 90 -95%. FiO2 requirement needs to be sustained for at least 15 minutes. 116
Control Group Intratracheal bolus surfactant 100mg/kg Anytime from randomisation to 72 hours of age If an infant meets failure criteria the infant is eligible to receive intratracheal bolus surfactant. At each site, . An FiO2 > 0.40 is consistent with the unit protocol to administer intratracheal bolus surfactant and aligns with the current standard of care. However, bolus intratracheal surfactant instillation will not be mandated and will be at the discretion of the clinician, who is guided by the unit protocol. Bolus surfactant may be administered by LISA, INSURE or intubation for surfactant delivery and ongoing mechanical ventilation. At most study sites, Beractant 100 mg/kg (Survanta) via LISA would be the standard of care for delivering intratracheal bolus surfactant. 116 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Inborn Birth Weight of 900 - 1999 g 2 - 24 hours of age at time of randomization Persistent fractional inspired oxygen (FiO2) of 0.25 – 0.35 on nCPAP at 5-7 cmH20 to maintain peripheral oxygen saturation of 90 -95%. FiO2 requirement needs to be sustained for at least 15 minutes. Administration of inotropes and/or intubation in the delivery room Apgar score ≤ 5 at 5 minutes Need for mechanical ventilation prior to enrolment Prior instillation of intratracheal bolus surfactant Pneumothorax that requires insertion of intercostal chest drain or needle thoracocentesis Life- threatening congenital anomaly Known or suspected chromosomal abnormality Known or suspected congenital infection including syphilis, cytomegalovirus or toxoplasmosis Enrolment in another treatment study with competing outcomes New born: 0 Day-1 Month 0 Day(s) 1 Day(s) Both
APPROVALS
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 31/01/2023 SAHPRA
Ethics Committee Address
Street address City Postal code Country
CSIR Reception Building 38a Meiring Naudé Road Brummeria Pretoria Gauteng 0083 South Africa
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 10/02/2023 UCT HREC
Ethics Committee Address
Street address City Postal code Country
Anzio Road Cape Town 7925 South Africa
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 08/06/2023 Stellenbosch University HREC
Ethics Committee Address
Street address City Postal code Country
Stellenbosch University Stellenbosch 7602 South Africa
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 17/01/2023 Witwatersrand University HREC
Ethics Committee Address
Street address City Postal code Country
1 Jan Smuts Avenue Braamfontein Johannesburg 2000 South Africa
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 30/01/2024 SAHPRA
Ethics Committee Address
Street address City Postal code Country
Kirkness Road Pretoria 0083 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome To determine if aerosolized surfactant given to preterm infants with RDS on nCPAP, compared with nCPAP alone, reduces the need for intratracheal bolus surfactant instillation in the first 72 hours of age. 72 hours of age
Secondary Outcome To compare the need for repeat intratracheal bolus surfactant dosing between groups To compare the need for mechanical ventilation between groups To compare the duration of mechanical ventilation, CPAP, high flow nasal cannula (HFNC) and supplementary oxygen between groups To compare the rate of adverse events and usually reported selected comorbidities of prematurity between groups (see Appendix for definitions) To compare the incidence of Bronchopulmonary Dysplasia (BPD), defined as the need for respiratory support at 36 weeks postmenstrual age, between groups To compare the incidence of death at any time between groups To compare the incidence of death or BPD between groups 72 hours of age
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Groote Schuur Hospital Neonatal Unit Anzio Road Cape Town 7925 South Africa
Tygerberg Hospital Neonatal High Care Unit Francie van Zijl Drive Parow Cape Town 7500 South Africa
Chris Hani Baragwanath Hospital Neonatal Unit Mother and Child Facility 26 Chris Hani Road Deipkloof Soweto 2013 South Africa
Mowbray Maternity Hospital High Care Unit 12 Hornsey Road Mowbray Cape Town 7700 South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
Aerogen Pharma Ltd 1660 S Amphlett Boulevard, Suite 360,San Mateo California 94402 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Aerogen Pharma 1660 S Amphlett Boulevard, Suite 360 San Mateo CA94402 United States of America Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Lloyd Tooke lloyd.tooke@uct.ac.za +270214046022 Groote Schuur Hospital Anzio Rd, Observatory
City Postal code Country Position/Affiliation
Cape Town 7925 South Africa National PI
Role Name Email Phone Street address
Scientific Enquiries Nyeleti Bicky Mthombeni regulatory@onqsa.co.za +270114310791 OnQ House 250 Market Street Fairland
City Postal code Country Position/Affiliation
Johannebsurg 2170 South Africa Project Operations Director
Role Name Email Phone Street address
Public Enquiries Jeanelle De Villiers regulatory@onqsa.co.za +270114310791 250 Market Street Fairland
City Postal code Country Position/Affiliation
Johannesburg 2170 South Africa Regional Operations Lead Africa
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes We will publish the results of this in medical journals so that other doctors can learn about it. These CSR reports will not include any of your personal information. The patient information will be used if it is needed for the study and may be kept for longer, where required, by law. Study records will be archived up to 10 years from the end of the study. All Patient data collected for the study will be de-identified and a study number will be used as patient identification. All the relevant study data will be shared with the relevant parties as mandated in the protocol ensuring patient identification protection at all times. Clinical Study Report Immediately after the Clinical Study Report has been finalized Open- labelled
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 Trial type 16/02/2023 SANCTR update CCT RCT
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Anticipated date of last follow up 12/09/2024 Protocol Amendment 03 16 Jan 2025 31 Dec 2026
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Target no of participants 12/09/2024 Protocol Amendment 03 232 332
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 23/06/2023 started recruiting Not yet recruiting Recruiting
Section Name Field Name Date Reason Old Value Updated Value
SecondaryID SecondaryID List 16/02/2023 Updated information APC-AF-CLN-004, Aerogen Pharma Ltd, 4787
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 25/07/2023 Additional site approved by SAHPRA and Stellenbosch University HREC Tygerberg Hospital Neonatal High Care Unit, Francie van Zijl Drive, Parow Cape Town, 7500, South Africa
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 25/07/2023 Additional site approved by SAHPRA and Wits University HREC. Chris Hani Baragwanath Hospital Neonatal Unit Mother and Child Facility, 26 Chris Hani Road, Deipkloof Soweto, 2013, South Africa
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 03/05/2024 Additional site added Mowbray Maternity Hospital High Care Unit, 12 Hornsey Road, Mowbray Cape Town, 7700, South Africa
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 25/07/2023 Additional site. True, Stellenbosch University HREC, Stellenbosch University, Stellenbosch, 7602, South Africa, , 08 Jun 2023, +27219389075, blanchep@sun.ac.za, 7030_14023_4737.pdf, M23/02/004
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 25/07/2023 Additional site True, Witwatersrand University HREC , 1 Jan Smuts Avenue, Braamfontein Johannesburg, 2000, South Africa, , 17 Jan 2023, +27112749278, jbryce@witshealth.co.za, 7030_14024_4737.pdf, 221112
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 03/05/2024 additional site approved True, UCT Human Research Ethics Committee, Anzio Road, Cape Town, 7925, South Africa, , 06 Feb 2024, +27216506346, hrec-enquiries@uct.ac.za, 7030_16548_4737.pdf, 681/2022
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 03/05/2024 Additional site approved True, UCT Human Research Ethics Committee, Anzio Road, Cape Town, 7925, South Africa, , 06 Feb 2024, +27216506346, hrec-enquiries@uct.ac.za, 7030_16548_4737.pdf, 681/2022 True, SAHPRA, Kirkness Road, Pretoria, 0083, South Africa, , 30 Jan 2024, +27125010300, hellen.moropyane@sahpra.org.za, 7030_16548_4737.pdf, 20221016
Section Name Field Name Date Reason Old Value Updated Value
Funding Source FundingSources List 16/02/2023 Updated Information Aerogan. , xxx, xxx, xxx, United States of America, Commercial Sector / Industry, , xxx, Primary Funder Aerogen Pharma Ltd, 1660 S Amphlett Boulevard, Suite 360,San Mateo, California, 94402, United States of America, Commercial Sector / Industry, , R 9 980 467, Primary Funder
Section Name Field Name Date Reason Old Value Updated Value
Contact People Contacs List 03/05/2024 Change in staffing Public Enquiries, Nyeleti Bicky , Mthombeni, Ms., regulatory@onqsa.co.za, , +270114310791, 250 Market Street Fairland , Johannesburg, 2170, South Africa, Project Operations Director Public Enquiries, Jeanelle , De Villiers, Mrs., regulatory@onqsa.co.za, , +270114310791, 250 Market Street Fairland , Johannesburg, 2170, South Africa, Regional Operations Lead Africa
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD description 16/02/2023 Updated Information Private Statement Included In The Informed Consent All Patient data collected for the study will be de-identified and a study number will be used as patient identification. All the relevant study data will be shared with the relevant parties as mandated in the protocol ensuring patient identification protection at all times.
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD description 20/02/2023 Updated Information All Patient data collected for the study will be de-identified and a study number will be used as patient identification. All the relevant study data will be shared with the relevant parties as mandated in the protocol ensuring patient identification protection at all times. We will publish the results of this in medical journals so that other doctors can learn about it. These CSR reports will not include any of your personal information. The patient information will be used if it is needed for the study and may be kept for longer, where required, by law. Study records will be archived up to 10 years from the end of the study.
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD description 23/02/2023 SANCTR admin We will publish the results of this in medical journals so that other doctors can learn about it. These CSR reports will not include any of your personal information. The patient information will be used if it is needed for the study and may be kept for longer, where required, by law. Study records will be archived up to 10 years from the end of the study. We will publish the results of this in medical journals so that other doctors can learn about it. These CSR reports will not include any of your personal information. The patient information will be used if it is needed for the study and may be kept for longer, where required, by law. Study records will be archived up to 10 years from the end of the study. All Patient data collected for the study will be de-identified and a study number will be used as patient identification. All the relevant study data will be shared with the relevant parties as mandated in the protocol ensuring patient identification protection at all times.
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD-Sharing time frame 16/02/2023 Updated information xxx 12 months after study completion
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD-Sharing time frame 20/02/2023 Updated information 12 months after study completion Immediately after the Clinical Study Report has been finalized
Section Name Field Name Date Reason Old Value Updated Value
Reporting Key access criteria 16/02/2023 Updated Information Controlled Open- labelled
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD URL 20/02/2023 Updated information https://www.aerogenpharma.com
Section Name Field Name Date Reason Old Value Updated Value
Reporting Study protocol document 16/02/2023 Updated Information Study Protocol, Informed Consent Form Clinical Study Report