Prematurity; ExtremePhase 1/2ParasNCT03641209
Extremely Low Gestatonal Age Infants' Paracetamol Study
A Phase 1/2 study testing Paracetamol 10mg/mL infusion solution in people with Prematurity; Extreme and Low Birthweight, Extremely (999 Grams or Less), run by Outi Aikio at 1 site in Finland.
Trial summary
In the present trial, early, intravenous paracetamol is compared to placebo in extremely premature or low birth weight infants in order to evaluate the effect on ductal closure. Read more about this study
- Who is it for?
- Ages Up to 96 hours
- Conditions the study is for
- Prematurity; Extreme, Low Birthweight, Extremely (999 Grams or Less)
- What is being tested?
- Paracetamol 10mg/mL infusion solution
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteFinland
- Study dates
- 3 Sep 2018to 1 Mar 2024
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 96 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Premature infants born before 28+0 gestation weeks and/or birth weight less than 1000g
Who cannot join
- Severe malformation or suspected chromosomal defect or other very severe life-threatening disease (e.g. very severe birth asphyxia or persistent pulmonary hypertension, etc.)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Extremely Low Gestational Age Infants' Paracetamol Study: a Randomized Trial
In the present trial, early, intravenous paracetamol is compared to placebo in extremely premature or low birth weight infants in order to evaluate the effect on ductal closure.
Read the detailed description
The purpose of this randomized, placebo-controlled, double-blind, phase 2, one center clinical trial is to study the efficacy and safety of early (< 96 h) intravenous paracetamol in prophylactic closure of ductus arteriosus in extremely premature (gestational age <28+0 wk, ELGA) or low birth weight (<1000 g, ELBW) infants. The infants born extremely preterm or low birth weight are a focus of the study, since a small phase 2 study on paracetamol failed to demonstrate contraction of ductus arteriosus.
In the investigator's previous cohort of ELGA/ELBW infants, the numbers of patients who needed any therapies for patent ductus arteriosus (PDA) were 29 (23%) in the paracetamol exposed group, and 90 (54%) in the control group. As demonstrated in a phase 2 study, the early paracetamol treatment induced the closure of ductus arteriosus: the mean (SD) ductal closure age was 177 (338) h in the whole paracetamol group. However, in the subgroup of ELGA infants born before 28 gestation weeks (n=14), the mean (SD) ductal closure ages in the paracetamol and placebo groups were 491 (504) h and 858 (719) h, respectively.
- Being tested
- Paracetamol 10mg/mL infusion solution, Placebo
- Keywords
- acetaminophen, ductus arteriosus, NIRS, intravenous
- Medical subject headings
- Premature Birth, Ductus Arteriosus, Patent
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Paracetamol 10mg/mL infusion solutionDrug
Also called acetaminophen, Paracetamol Fresenius Kabi 10 mg/mL infusion solution
Intravenous paracetamol solution for infusion
PlaceboOther
Also called Natriumklorid Braun 4,5mg/mL solution for infusion
Half physiological saline solution as the non-active placebo solution
| Study group | Role | What they receive |
|---|---|---|
| Paracetamol | Experimental | Paracetamol 10 mg/mL infusion solution, intravenous loading dose 20 mg/kg, followed by maintenance dose 7.5 mg/kg every 6 h up to 9 days Receives: Drug: Paracetamol 10mg/mL infusion solution |
| Placebo | Placebo comparator | 0.45% sodium chloride (NaCl) solution, equal amounts in mL as would have been given the experimental drug Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ductal closure
Postnatal age of the observed closure of ductus arteriosus
Measured: Neonatal intensive care unit (NICU) treatment period up to 13 weeks
Secondary outcomes (9)
Near-infrared spectroscopy values
Near-infrared spectroscopy values
Measured: Study drug period up to 10 days
Paracetamol serum levels
Paracetamol serum levels
Measured: Study drug period up to 10 days
Paracetamol side effects
Any observed or detected paracetamol side effects
Measured: Neonatal intensive care unit (NICU) treatment period up to 13 weeks
PDA
Open ductus arteriosus without any traditional PDA therapies
Measured: Neonatal intensive care unit (NICU) treatment period up to 13 weeks
PDA, treated
The need for PDA therapies (ibuprofen, paracetamol, ligation)
Measured: Neonatal intensive care unit (NICU) treatment period up to 13 weeks
Ventilatory assist
The duration of any ventilation assist, days
Measured: Neonatal intensive care unit (NICU) treatment period up to 13 weeks
Complications of prematurity
The long term complications of prematurity (moderate-to-severe bronchopulmonary dysplasia (BPD), intraventricular hemorrhage gr 2-4, moderate to severe necrotizing enterocolitis, retinopathy of prematurity (ROP) needing therapy)
Measured: The first hospitalization period up to 19 weeks
Long term morbidity
Other long-term morbidity
Measured: The first hospitalization period up to 19 weeks
Mortality
Mortality
Measured: The first hospitalization period up to 19 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2018
- Study start3 Sep 2018
- Primary completion3 Nov 2023
- Study completion1 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Prematurity; ExtremeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, controlled, one center trial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Outi Aikio
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Outi Aikio, University of Oulu
- Investigators
- Outi Aikio, MD, PhD, Principal investigator, Oulu University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03641209
- Sponsor's protocol ID
- 39/2018
- Acronym
- Paras
- Status last verified
- Mar 2024
- First submitted
- 3 Aug 2018
- Last updated
- 15 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Juujarvi S, Saarela T, Hallman M, Aikio O. Intravenous paracetamol was associated with closure of the ductus arteriosus in extremely premature infants. Acta Paediatr. 2018 Apr;107(4):605-610. doi: 10.1111/apa.14137. Epub 2017 Nov 17.
PubMed 29105147Harkin P, Harma A, Aikio O, Valkama M, Leskinen M, Saarela T, Hallman M. Paracetamol Accelerates Closure of the Ductus Arteriosus after Premature Birth: A Randomized Trial. J Pediatr. 2016 Oct;177:72-77.e2. doi: 10.1016/j.jpeds.2016.04.066. Epub 2016 May 20.
PubMed 27215779Harma A, Aikio O, Hallman M, Saarela T. Intravenous Paracetamol Decreases Requirements of Morphine in Very Preterm Infants. J Pediatr. 2016 Jan;168:36-40. doi: 10.1016/j.jpeds.2015.08.003. Epub 2015 Aug 29.
PubMed 26323200Aikio O, Harkin P, Saarela T, Hallman M. Early paracetamol treatment associated with lowered risk of persistent ductus arteriosus in very preterm infants. J Matern Fetal Neonatal Med. 2014 Aug;27(12):1252-6. doi: 10.3109/14767058.2013.854327. Epub 2013 Oct 31.
PubMed 24111688
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Extremely Low Gestational Age Infants' Paracetamol Study: a Randomized Trial
- ClinicalTrials.gov ID
- NCT03641209
- Acronym / sponsor ID
- Paras / 39/2018
- Keywords
- acetaminophen, ductus arteriosus, NIRS, intravenous
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Outi AikioUniversity, hospital or other
- Study start
- 3 Sep 2018 (actual)
- Primary completion
- 3 Nov 2023 (actual)
- Study completion
- 1 Mar 2024 (actual)
- First posted
- 21 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In the present trial, early, intravenous paracetamol is compared to placebo in extremely premature or low birth weight infants in order to evaluate the effect on ductal closure.
Detailed description
The purpose of this randomized, placebo-controlled, double-blind, phase 2, one center clinical trial is to study the efficacy and safety of early (< 96 h) intravenous paracetamol in prophylactic closure of ductus arteriosus in extremely premature (gestational age <28+0 wk, ELGA) or low birth weight (<1000 g, ELBW) infants. The infants born extremely preterm or low birth weight are a focus of the study, since a small phase 2 study on paracetamol failed to demonstrate contraction of ductus arteriosus.
In the investigator's previous cohort of ELGA/ELBW infants, the numbers of patients who needed any therapies for patent ductus arteriosus (PDA) were 29 (23%) in the paracetamol exposed group, and 90 (54%) in the control group. As demonstrated in a phase 2 study, the early paracetamol treatment induced the closure of ductus arteriosus: the mean (SD) ductal closure age was 177 (338) h in the whole paracetamol group. However, in the subgroup of ELGA infants born before 28 gestation weeks (n=14), the mean (SD) ductal closure ages in the paracetamol and placebo groups were 491 (504) h and 858 (719) h, respectively.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Randomized, controlled, one center trial
| Arm | Type | Receives |
|---|---|---|
| Paracetamol | Experimental | Drug: Paracetamol 10mg/mL infusion solutionParacetamol 10 mg/mL infusion solution, intravenous loading dose 20 mg/kg, followed by maintenance dose 7.5 mg/kg every 6 h up to 9 days |
| Placebo | Placebo comparator | Other: Placebo0.45% sodium chloride (NaCl) solution, equal amounts in mL as would have been given the experimental drug |
Who may qualify
- Ages
- Up to 96 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- Premature infants born before 28+0 gestation weeks and/or birth weight less than 1000g
Key exclusion criteria (1 listed)
- Severe malformation or suspected chromosomal defect or other very severe life-threatening disease (e.g. very severe birth asphyxia or persistent pulmonary hypertension, etc.)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Paracetamol 10mg/mL infusion solutionAlso: acetaminophen, Paracetamol Fresenius Kabi 10 mg/mL infusion solutionIntravenous paracetamol solution for infusion | Drug | Paracetamol |
| PlaceboAlso: Natriumklorid Braun 4,5mg/mL solution for infusionHalf physiological saline solution as the non-active placebo solution | Other | Placebo |
Primary outcome
Ductal closure
Time frame: Neonatal intensive care unit (NICU) treatment period up to 13 weeks
Postnatal age of the observed closure of ductus arteriosus
9 secondary outcomes
Near-infrared spectroscopy values
Time frame: Study drug period up to 10 days
Paracetamol serum levels
Time frame: Study drug period up to 10 days
Paracetamol side effects
Time frame: Neonatal intensive care unit (NICU) treatment period up to 13 weeks
PDA
Time frame: Neonatal intensive care unit (NICU) treatment period up to 13 weeks
PDA, treated
Time frame: Neonatal intensive care unit (NICU) treatment period up to 13 weeks
Ventilatory assist
Time frame: Neonatal intensive care unit (NICU) treatment period up to 13 weeks
Complications of prematurity
Time frame: The first hospitalization period up to 19 weeks
Long term morbidity
Time frame: The first hospitalization period up to 19 weeks
Mortality
Time frame: The first hospitalization period up to 19 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2024.
- Background: PubMed 29105147Juujarvi S, Saarela T, Hallman M, Aikio O. Intravenous paracetamol was associated with closure of the ductus arteriosus in extremely premature infants. Acta Paediatr. 2018 Apr;107(4):605-610. doi: 10.1111/apa.14137. Epub 2017 Nov 17.
- Background: PubMed 27215779Harkin P, Harma A, Aikio O, Valkama M, Leskinen M, Saarela T, Hallman M. Paracetamol Accelerates Closure of the Ductus Arteriosus after Premature Birth: A Randomized Trial. J Pediatr. 2016 Oct;177:72-77.e2. doi: 10.1016/j.jpeds.2016.04.066. Epub 2016 May 20.
- Background: PubMed 26323200Harma A, Aikio O, Hallman M, Saarela T. Intravenous Paracetamol Decreases Requirements of Morphine in Very Preterm Infants. J Pediatr. 2016 Jan;168:36-40. doi: 10.1016/j.jpeds.2015.08.003. Epub 2015 Aug 29.
- Background: PubMed 24111688Aikio O, Harkin P, Saarela T, Hallman M. Early paracetamol treatment associated with lowered risk of persistent ductus arteriosus in very preterm infants. J Matern Fetal Neonatal Med. 2014 Aug;27(12):1252-6. doi: 10.3109/14767058.2013.854327. Epub 2013 Oct 31.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Outi Aikio, MD, PhD principal investigator
Oulu University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Paracetamol 10mg/mL infusion solution in people with Prematurity; Extreme and Low Birthweight, Extremely (999 Grams or Less), run by Outi Aikio at 1 site in Finland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Finland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ductal closure (time frame: Neonatal intensive care unit (NICU) treatment period up to 13 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03641209, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2024.