免费获得国外相关药品，最快 1 个工作日回馈药物信息
出境医 / 临床实验 / Indomethacin PK-PD in Extremely Preterm Neonates (INDO)
Indomethacin PK-PD in Extremely Preterm Neonates (INDO)
Study Description
Brief Summary:
This is a phase II open-label study evaluating the pharmacokinetics and pharmacodynamics of targeted early use of indomethacin for PDA treatment in preterm neonates <27 weeks' gestational age.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Patent Ductus Arteriosus After Premature Birth | Drug: Indomethacin Injection | Phase 2 |
Detailed Description:
Neonates will be enrolled following an echocardiogram performed within 12 hours after birth that confirms an open PDA (with no other contraindications for indomethacin treatment). After enrollment, neonates will receive intravenous indomethacin at a dose of 0.1mg/kg every 24 hours for 3 days. Indomethacin levels will be measured at regular intervals. Urine output and serum electrolytes will be monitored prior to each dose of indomethacin. An echocardiogram will be repeated after completion of indomethacin treatment (between 72-120 hours of age) to reassess the status of PDA.
Study Design
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 25 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Pharmacokinetics and Pharmacodynamics of Indomethacin Used for PDA Treatment in Extremely Preterm Neonates <27 Weeks Gestational Age |
| Estimated Study Start Date : | January 2020 |
| Estimated Primary Completion Date : | August 2021 |
| Estimated Study Completion Date : | February 2022 |
Arms and Interventions
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Neonates with an open PDA
Neonates born between 23 (0/7) and 26 (6/7) weeks gestational age with an open PDA, according to clinical protocol criteria, and no contraindication to the use of indomethacin.
|
Drug: Indomethacin Injection
The dose of indomethacin will be 0.1 mg/kg/dose, based on birth weight, intravenously every 24 hours for a total of 3 doses. Doses 2 and 3 may be administered between 23.5 and 24.5 hours after the previous dose. Doses will be rounded to two significant figures.
|
Outcome Measures
Primary Outcome Measures :
- Area under the curve from serial Indomethacin levels [ Time Frame: At 48 hour following the last dose ]Blood samples will be drawn from patients to determine the serum indomethacin levels to determine the area under the curve
Secondary Outcome Measures :
- Percentage of Participants with Patent Ductus Arteriosus Closure [ Time Frame: Within 48 hrs after the last dose ]Confirmed by echocardiogram
- Percentage of Participants with Intraventricular hemorrhage [ Time Frame: Within the first 7 days of life. ]Confirmed by cranial ultrasound performed and graded using Papile's classification system
- Duration of mechanical ventilation of each patient [ Time Frame: trough hospital discharge, an average of up to 36 weeks gestational age ]Number of days the infant was intubated and ventilated.
- Percentage of Participants with Adverse Events [ Time Frame: trough hospital discharge, an average of up to 36 weeks gestational age ]development of any type A adverse reactions in the infants receiving indomethacin therapy
Eligibility Criteria
| Ages Eligible for Study: | 23 Weeks to 26 Weeks (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Male or female infant born between 23 (0/7) and 26 (6/7) week GA
- Infant diagnosed with PDA according to clinical protocol criteria
- Able to adhere to indomethacin administration protocol
- The patient is born in the study center.
- Subject's parent(s)/legal guardian(s) has provided signed and dated informed consent and authorization to use protected health information, as required by national and local regulations.
- In the investigator's opinion, the subject's parent(s)/legal guardian(s) understand(s) and can comply with protocol requirements, instructions, and protocol-stated restrictions, and is likely to complete the study as planned.
Exclusion Criteria:
- known major congenital malformations (renal, cardiac, gastrointestinal and central nervous system)
- genetic syndromes-inborn errors of metabolism
- severe renal compromise
- intrauterine growth retardation with birth weight <3rd centile
- thrombocytopenia <50,000/mm3
- moderate to severe pulmonary hypertension
- clinical sepsis -meningitis- hepatitis
- anticipated drug-drug-interactions (specifically CYP2C9, CYP2C19 and UGT 1-1)
Contacts and Locations
Contacts
| Contact: Deepak Louis, MD | 2048981140 | dlouis@exchange.hsc.mb.ca | |
| Contact: Abin Chandrakumar, PharmD, MSc | 2045945359 | achandrakumar@chrim.ca |
Locations
| Canada, Manitoba | |
| St. Boniface General Hospital Research Centre | |
| Winnipeg, Manitoba, Canada, R2H 2A6 | |
| Health Sciences Centre | |
| Winnipeg, Manitoba, Canada, R3A 1R9 | |
Sponsors and Collaborators
University of Manitoba
St. Boniface Hospital
Health Sciences Centre, Winnipeg, Manitoba
University at Buffalo
Investigators
| Principal Investigator: | Deepak Louis, MD | University of Manitoba |
| Tracking Information | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| First Submitted Date ICMJE | May 27, 2019 | ||||||||
| First Posted Date ICMJE | July 18, 2019 | ||||||||
| Last Update Posted Date | September 25, 2019 | ||||||||
| Estimated Study Start Date ICMJE | January 2020 | ||||||||
| Estimated Primary Completion Date | August 2021 (Final data collection date for primary outcome measure) | ||||||||
| Current Primary Outcome Measures ICMJE |
Area under the curve from serial Indomethacin levels [ Time Frame: At 48 hour following the last dose ] Blood samples will be drawn from patients to determine the serum indomethacin levels to determine the area under the curve
|
||||||||
| Original Primary Outcome Measures ICMJE | Same as current | ||||||||
| Change History | |||||||||
| Current Secondary Outcome Measures ICMJE |
|
||||||||
| Original Secondary Outcome Measures ICMJE | Same as current | ||||||||
| Current Other Pre-specified Outcome Measures | Not Provided | ||||||||
| Original Other Pre-specified Outcome Measures | Not Provided | ||||||||
| Descriptive Information | |||||||||
| Brief Title ICMJE | Indomethacin PK-PD in Extremely Preterm Neonates | ||||||||
| Official Title ICMJE | Pharmacokinetics and Pharmacodynamics of Indomethacin Used for PDA Treatment in Extremely Preterm Neonates <27 Weeks Gestational Age | ||||||||
| Brief Summary | This is a phase II open-label study evaluating the pharmacokinetics and pharmacodynamics of targeted early use of indomethacin for PDA treatment in preterm neonates <27 weeks' gestational age. | ||||||||
| Detailed Description | Neonates will be enrolled following an echocardiogram performed within 12 hours after birth that confirms an open PDA (with no other contraindications for indomethacin treatment). After enrollment, neonates will receive intravenous indomethacin at a dose of 0.1mg/kg every 24 hours for 3 days. Indomethacin levels will be measured at regular intervals. Urine output and serum electrolytes will be monitored prior to each dose of indomethacin. An echocardiogram will be repeated after completion of indomethacin treatment (between 72-120 hours of age) to reassess the status of PDA. | ||||||||
| Study Type ICMJE | Interventional | ||||||||
| Study Phase ICMJE | Phase 2 | ||||||||
| Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
||||||||
| Condition ICMJE | Patent Ductus Arteriosus After Premature Birth | ||||||||
| Intervention ICMJE | Drug: Indomethacin Injection
The dose of indomethacin will be 0.1 mg/kg/dose, based on birth weight, intravenously every 24 hours for a total of 3 doses. Doses 2 and 3 may be administered between 23.5 and 24.5 hours after the previous dose. Doses will be rounded to two significant figures.
|
||||||||
| Study Arms ICMJE | Experimental: Neonates with an open PDA
Neonates born between 23 (0/7) and 26 (6/7) weeks gestational age with an open PDA, according to clinical protocol criteria, and no contraindication to the use of indomethacin.
Intervention: Drug: Indomethacin Injection
|
||||||||
| Publications * | Not Provided | ||||||||
|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
|||||||||
| Recruitment Information | |||||||||
| Recruitment Status ICMJE | Not yet recruiting | ||||||||
| Estimated Enrollment ICMJE |
25 | ||||||||
| Original Estimated Enrollment ICMJE | Same as current | ||||||||
| Estimated Study Completion Date ICMJE | February 2022 | ||||||||
| Estimated Primary Completion Date | August 2021 (Final data collection date for primary outcome measure) | ||||||||
| Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
|
||||||||
| Sex/Gender ICMJE |
|
||||||||
| Ages ICMJE | 23 Weeks to 26 Weeks (Child) | ||||||||
| Accepts Healthy Volunteers ICMJE | No | ||||||||
| Contacts ICMJE |
|
||||||||
| Listed Location Countries ICMJE | Canada | ||||||||
| Removed Location Countries | |||||||||
| Administrative Information | |||||||||
| NCT Number ICMJE | NCT04025177 | ||||||||
| Other Study ID Numbers ICMJE | B2018:095 | ||||||||
| Has Data Monitoring Committee | Yes | ||||||||
| U.S. FDA-regulated Product |
|
||||||||
| IPD Sharing Statement ICMJE |
|
||||||||
| Responsible Party | University of Manitoba | ||||||||
| Study Sponsor ICMJE | University of Manitoba | ||||||||
| Collaborators ICMJE |
|
||||||||
| Investigators ICMJE |
|
||||||||
| PRS Account | University of Manitoba | ||||||||
| Verification Date | May 2019 | ||||||||
|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
|||||||||
