Canadian National PDA Treatment Study

NCT04347720 | Completed FDA Drug

• 1 other identifier: 1025627
• Study Type: observational
• Target: 1,663
• Locations: 1 country
• Sites: 22

Brief Summary

Patent ductus arteriosus (PDA) is the most common cardiovascular problem that develops in preterm infants. Persistent PDA may result in higher rates of death, chronic lung disease (CLD), pulmonary hemorrhage, necrotizing enterocolitis (NEC), acute kidney injury (AKI), intraventricular hemorrhage (IVH) and cerebral palsy. Currently available options to treat a PDA include indomethacin, ibuprofen or acetaminophen followed by surgical or interventional closure of the PDA if medical therapy fails. Wide variation exists in PDA treatment practices across Canada. A survey conducted through the Canadian Neonatal Network (CNN) in 2019 showed that the most common choice of initial pharmacotherapy is standard dose ibuprofen. In view of the high pharmacotherapy failure rate with standard dose ibuprofen, there is a growing use of higher doses of ibuprofen with increasing postnatal age (with 32% of respondents currently adopting this practice) in spite of the fact that effectiveness and safety of higher ibuprofen doses have not been established in extremely preterm infants \[\<29 weeks gestational age (GA)\]. In view of this large practice variation across Canadian neonatal intensive care units (NICUs), we are planning a comparative effectiveness study of the different primary pharmacotherapeutic agents used to treat the PDA in preterm infants. Aims Primary: To compare the primary pharmacotherapeutic practices for PDA closure and evaluate their impact on clinical outcomes in extremely preterm infants (\<29 weeks GA) Secondary: To understand the relevance of pharmacotherapeutic PDA treatment with respect to clinical outcomes in the real world. Methods: Participants: Extremely preterm infants (\<29 weeks gestational age) with an echocardiography confirmed PDA who will be treated according to attending team Interventions:

1. 1.Standard dose ibuprofen \[10-5-5 regimen, i.e., 10mg/kg followed by 2 doses of 5mg/kg at 24h intervals\]
2. 2.Adjustable dose ibuprofen \[10-5-5 regimen if treated within the first week. Higher doses of ibuprofen up to a 20-10-10 regimen if treated after the postnatal age cut-off for lower dose as per the local center policy\]
3. 3.Intravenous indomethacin \[0.1-0.3mg/kg every 12-24h for a total of 3 doses\].
4. 4.Acetaminophen \[Oral/intravenous\] (15mg/kg every 6h) for 3-7 days

Conditions

Patent Ductus Arteriosus; Extreme Prematurity

Keywords

indomethacin; ibuprofen; acetaminophen

Outcome Measures

Primary Outcomes (1)

• Failure of primary pharmacotherapy

  Receipt of further medical and/or surgical/interventional treatment following an initial course of pharmacotherapy

  through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)

Secondary Outcomes (10)

• Receipt of 2nd course of pharmacotherapy

  through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)

• Surgical/interventional PDA closure

  through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)

• Chronic lung disease

  birth through 36 weeks post menstrual age

• Necrotizing enterocolitis

  through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)

• Severe intraventricular hemorrhage

  through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)

Study Arms (6)

Indomethacin Arm

Intravenous indomethacin at 0.1-0.3 mg/kg IV every 12-24h for a total of 3 doses as choice of initial pharmacotherapy.

Drug: Indomethacin

Standard dose ibuprofen Arm

Standard dose ibuprofen \[Oral/intravenous\] at 10 mg/kg followed by 2 doses of 5mg/kg at 24 h intervals irrespective of postnatal age as choice of initial pharmacotherapy.

Drug: Ibuprofen

Adjustable dose ibuprofen Arm

Adjustable dose ibuprofen \[Oral/intravenous\] as choice of initial pharmacotherapy. The dose of ibuprofen will be 10 mg/kg followed by 2 doses of 5 mg/kg at 24 h intervals if treated within the first 7 days after birth. Higher doses of ibuprofen up to 20 mg/kg followed by 2 doses of 10 mg/kg at 24 h intervals if treated after the postnatal age cut-off for lower dose as per the local center policy

Drug: Ibuprofen

Acetaminophen Arm

Acetaminophen \[Oral/intravenous\] at 15mg/kg every 6h for 3-7 days as choice of initial pharmacotherapy.

Drug: Acetaminophen

Control group

Infants \<29 weeks GA with echocardiography-confirmed PDA but never received any pharmacotherapy

Reference group

Infants \<29 weeks GA who were never diagnosed with PDA

Interventions

Indomethacin DRUG

Intravenous formulation

Also known as: indocid

Indomethacin Arm

Ibuprofen DRUG

Intravenous and oral formulations

Also known as: Advil, NeoProfen

Adjustable dose ibuprofen Arm; Standard dose ibuprofen Arm

Acetaminophen DRUG

Intravenous and oral formulations

Also known as: paracetamol

Acetaminophen Arm

Eligibility Criteria

• Age: Up to 12 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study Population

All infants born less than 29 weeks of gestation admitted to the participating sites will be included in the study. The population of interest will be those preterm infants \<29 weeks gestational age (including outborns) with echocardiography confirmed PDA who will be treated according to attending team. Infants \<29 weeks GA with echocardiography-confirmed PDA but never received treatment will be included as the control population. Infants \<29 weeks GA who were never diagnosed with PDA will be included as the reference population

You may qualify if:

• Extremely preterm infants (\<29 weeks gestational age) with an echocardiography confirmed PDA who will be treated according to attending team

You may not qualify if:

• Any infant who received pharmacotherapy for a clinically symptomatic PDA without prior echocardiographic confirmation of the presence of PDA will be excluded from all analyses.

Sponsors & Collaborators

• IWK Health Centre: lead
• Provincial Health Services Authority British Columbia: collaborator
• Children's Hospital of Eastern Ontario: collaborator
• CHU de Quebec-Universite Laval: collaborator
• Foothills Medical Centre: collaborator
• Victoria General Hospital: collaborator
• The Hospital for Sick Children: collaborator
• Health Sciences Centre, Winnipeg, Manitoba: collaborator
• St. Justine's Hospital: collaborator
• Queen's University: collaborator
• MOUNT SINAI HOSPITAL: collaborator
• Royal Alexandra Hospital: collaborator
• Regina General Hospital: collaborator
• Royal University Hospital Foundation: collaborator
• St. Boniface Hospital: collaborator
• The Moncton Hospital: collaborator
• Horizon Health Network: collaborator
• Sunnybrook Health Sciences Centre: collaborator
• Windsor Regional Hospital: collaborator
• Royal Columbian Hospital Foundation: collaborator
• Centre de recherche du Centre hospitalier universitaire de Sherbrooke: collaborator
• London Health Sciences Centre: collaborator
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (22)

Foothills Medical Centre

Calgary, Alberta, Canada

Location

Royal Alexandra Hospital

Edmonton, Alberta, Canada

Location

Royal Columbian Hospital

New Westminster, British Columbia, Canada

Location

British Columbia Women's Hospital

Vancouver, British Columbia, Canada

Location

Victoria General Hospital

Victoria, British Columbia, Canada

Location

Health Sciences Centre

Winnipeg, Manitoba, Canada

Location

St. Boniface General Hospital

Winnipeg, Manitoba, Canada

Location

The Moncton Hospital

Moncton, New Brunswick, Canada

Location

Saint John Regional Hospital

Saint John, New Brunswick, Canada

Location

IWK Health Center

Halifax, Nova Scotia, B3K 6R8, Canada

Location

Kingston Health Sciences Centre

Kingston, Ontario, Canada

Location

London Health Sciences Centre

London, Ontario, Canada

Location

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada

Location

Hospital for Sick Children

Toronto, Ontario, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Location

Windsor Regional Hospital

Windsor, Ontario, Canada

Location

CHU Sainte-Justine

Montreal, Quebec, Canada

Location

Centre Hospitalier Universitaire de Quebec

Québec, Quebec, Canada

Location

Centre Hospitalier Universitaire de Sherbrooke

Sherbrooke, Quebec, Canada

Location

Regina General Hospital

Regina, Saskatchewan, Canada

Location

Royal University Hospital

Saskatoon, Saskatchewan, Canada

Location

Related Publications (1)

• Mitra S, Jain A, Ting JY, Ben Fadel N, Drolet C, Abou Mehrem A, Soraisham A, Jasani B, Louis D, Lapointe A, Dorling J, Khurshid F, Hyderi A, Kumaran K, Bodani J, Weisz D, Alvaro R, Adie M, Stavel M, Morin A, Bhattacharya S, Kanungo J, Canning R, Ye XY, Hatfield T, Gardner CE, Shah P. Relative effectiveness and safety of pharmacotherapeutic agents for patent ductus arteriosus (PDA) in preterm infants: a protocol for a multicentre comparative effectiveness study (CANRxPDA). BMJ Open. 2021 May 5;11(5):e050682. doi: 10.1136/bmjopen-2021-050682.

  PMID: 33952559 DERIVED

Related Links

• Project funding information on the Canadian Institutes of Health Research (CIHR) Funding Decision Database

MeSH Terms

Conditions

Ductus Arteriosus, Patent

Interventions

Indomethacin; Ibuprofen; Acetaminophen

Condition Hierarchy (Ancestors)

Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Acetanilides; Anilides; Amides; Aniline Compounds; Amines

Study Officials

• Souvik Mitra, MD, MSc

  IWK Health Center, Halifax, Canada

  PRINCIPAL INVESTIGATOR

• Amish Jain, MBBS, PhD

  Mount Sinai Hospital, Canada

  PRINCIPAL INVESTIGATOR

• Prakeshkumar Shah, MD, FRCPC

  Mount Sinai Hospital, Canada

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 20 Weeks
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: April 12, 2020
• First Posted: April 15, 2020
• Study Start: January 1, 2020
• Primary Completion: July 31, 2023
• Study Completion: December 31, 2023
• Last Updated: June 21, 2024

Record last verified: 2024-06

Locations

CA (22)