PDAPhase 3NCT01755728
Paracetamol (Acetaminophen) for Closure of PDA in Preterm Infants
A Phase 3 study testing Paracetamol, Ibuprofen and Closure of PDA in people with PDA, run by Hillel Yaffe Medical Center at 1 site in Israel.
Trial summary
There is a report that acetaminophen may have a role in pharmacological closure of PDA (Patent arterial duct) in preterm infants. The investigators conducted this open label non randomized and non control study to try to support that report. Read more about this study
- Who is it for?
- Ages Up to 4 months
- Conditions the study is for
- PDA
- What is being tested?
- Paracetamol, Ibuprofen and Closure of PDA
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteIsrael
- Study dates
- 1 Jan 2013to 31 Dec 2018
- Phase
- Phase 3
- 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 4 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Preterm infants with symptomatic PDA who could not be treated with ibuprofen
Who cannot join
- None
Trial locations and contacts
1 site in 1 country.
Israel1 site
Neonatal intensive care unit, Hillel Yaffe medical center
Hadera, 38100
About this study
There is a report that acetaminophen may have a role in pharmacological closure of PDA (Patent arterial duct) in preterm infants.
The investigators conducted this open label non randomized and non control study to try to support that report.
Read the detailed description
In-uteri, the arterial duct connects between the aorta and the main pulmonary artery, thus bypassing the lungs. Since the high pulmonary pressure and the low systemic pressure, the shunt trough the arterial duct in that time is right to left.
After birth, systemic pressure rises and pulmonary pressure declines. As oxygen saturation rises, and prostaglandin secretion, the arterial duct closes, usually. In preterm infants, the arterial duct may remain open after birth. At this tume the shunt would be left to right, that would cause pulmonary congestion, and systemic hypoperfusion.
Ibuprofen is the treatment of choice for PDA in preterm infants. Yet, ibuprofen is not effective after two weeks of age. Moreover, there are situations that prevent treatment with ibuprofen, such as thrombocytopenia or renal failure. Surgical closure of arterial duct is an alternative treatment, if ibuprofen is contraindicated, or if it fails.
Lastly, there was a report that acetaminophen may have a role in pharmacological closure of PDA in preterm infants.
The investigators conducted this open label non randomized and non control study to try to support that report.
- Conditions
- PDA
- Being tested
- Paracetamol, Ibuprofen, Closure of PDA
- Keywords
- Paracetamol, Acetaminophen, PDA, Preterm infants
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ParacetamolDrug
Also called Acetaminophen
Per gavage paracetamol 15 mg/kg every 6 hours, for up to 7 days.
IbuprofenDrug
Per Gavage ibuprofen 10mg/kg x 3/d for up to 5 days Gold standard per literature
Closure of PDAProcedure or surgery
Open surgery for closure of PDA
| Study group | Role | What they receive |
|---|---|---|
| No known PDA | No intervention | For all infants, we do echo cardiogram study only if they are suspected of having PDA, due to sings and symptoms. Hence, we do not do echo cardiogram study to most of the infants. |
| Ibuprofen | Active comparator | If there is a PDA, that should be treated, and the infant is less than 2 weeks of age, we use ibuprofen, as this is the gold standard in literature. Receives: Drug: Ibuprofen |
| Surgical closure of PDA | Active comparator | Infants with symptomatic PDA, who had to be treated, but could not be treated by ibuprofen, either due to age (> 2 weeks) or due ibuprofen contraindications (thrombocytopenia or renal failure), whose could not be treated by paracetamol (either because of parents' refuse or because they were on nothing per os protocol due to other disease), for whom surgery was the treatment of choice to close the arterial duct. Receives: Procedure: Closure of PDA |
| Paracetamol | Experimental | Infants with symptomatic PDA who could not be treated with ibuprofen, and their parents agreed and they could be treated with paracetamol. Receives: Drug: Paracetamol |
| DA closed spontaneously | No intervention | Infants with PDA, who did not get any treatment for it, and the duct was closed spontaneously. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Closure of arterial duct - yes / No
Echo-cardiogram that will give exact answer to the question: "was the arterial duct closed"?
Measured: 1 week
Secondary outcomes (1)
Need for surgical closure of arterial duct
The clinical state of the infant will guide the team to ask the parents and the chest surgeon to surgically close the arterial duct
Measured: 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2012 (estimated)
- Study start1 Jan 2013
- Primary completion31 Dec 2018
- Study completion31 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for PDAStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hillel Yaffe Medical Center
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Erez Nadir, MD, Hillel Yaffe Medical Center
- Investigators
- Erez Nadir, MD, Principal investigator, Hillel Yaffe medical center, Hadera, Israel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01755728
- Sponsor's protocol ID
- 77-12-HYMC-CTIL
- Status last verified
- Aug 2019
- First submitted
- 16 Dec 2012
- Last updated
- 6 Aug 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Hammerman C, Bin-Nun A, Markovitch E, Schimmel MS, Kaplan M, Fink D. Ductal closure with paracetamol: a surprising new approach to patent ductus arteriosus treatment. Pediatrics. 2011 Dec;128(6):e1618-21. doi: 10.1542/peds.2011-0359. Epub 2011 Nov 7.
PubMed 22065264Hammerman C, Bin-Nun A, Kaplan M. Managing the patent ductus arteriosus in the premature neonate: a new look at what we thought we knew. Semin Perinatol. 2012 Apr;36(2):130-8. doi: 10.1053/j.semperi.2011.09.023.
PubMed 22414884Oncel MY, Yurttutan S, Uras N, Altug N, Ozdemir R, Ekmen S, Erdeve O, Dilmen U. An alternative drug (paracetamol) in the management of patent ductus arteriosus in ibuprofen-resistant or contraindicated preterm infants. Arch Dis Child Fetal Neonatal Ed. 2013 Jan;98(1):F94. doi: 10.1136/archdischild-2012-302044. Epub 2012 May 18. No abstract available.
PubMed 22611117Peterson RG. Consequences associated with nonnarcotic analgesics in the fetus and newborn. Fed Proc. 1985 Apr;44(7):2309-13.
PubMed 3884385Rudolph AM. Effects of aspirin and acetaminophen in pregnancy and in the newborn. Arch Intern Med. 1981 Feb 23;141(3 Spec No):358-63. doi: 10.1001/archinte.141.3.358.
PubMed 7469626Simbi KA, Secchieri S, Rinaldo M, Demi M, Zanardo V. In utero ductal closure following near-term maternal self-medication with nimesulide and acetaminophen. J Obstet Gynaecol. 2002 Jul;22(4):440-1. doi: 10.1080/01443610220141489. No abstract available.
PubMed 12521476Weintraub A, Mankuta D. Dipyrone-induced oligohydramnios and ductus arteriosus restriction. Isr Med Assoc J. 2006 Oct;8(10):722-3. No abstract available.
PubMed 17125127Burdan F, Staroslawska E, Szumilo J. Prenatal tolerability of acetaminophen and other over-the-counter non-selective cyclooxygenase inhibitors. Pharmacol Rep. 2012;64(3):521-7. doi: 10.1016/s1734-1140(12)70847-2.
PubMed 22814005
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Paracetamol (Acetaminophen) for Closure of PDA in Preterm Infants
- ClinicalTrials.gov ID
- NCT01755728
- Acronym / sponsor ID
- 77-12-HYMC-CTIL
- Conditions
- PDA
- Keywords
- Paracetamol, Acetaminophen, PDA, Preterm infants
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Hillel Yaffe Medical CenterOther government
- Study start
- 1 Jan 2013 (actual)
- Primary completion
- 31 Dec 2018 (actual)
- Study completion
- 31 Dec 2018 (actual)
- First posted
- 24 Dec 2012 (estimated)
- 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.
There is a report that acetaminophen may have a role in pharmacological closure of PDA (Patent arterial duct) in preterm infants.
The investigators conducted this open label non randomized and non control study to try to support that report.
Detailed description
In-uteri, the arterial duct connects between the aorta and the main pulmonary artery, thus bypassing the lungs. Since the high pulmonary pressure and the low systemic pressure, the shunt trough the arterial duct in that time is right to left.
After birth, systemic pressure rises and pulmonary pressure declines. As oxygen saturation rises, and prostaglandin secretion, the arterial duct closes, usually. In preterm infants, the arterial duct may remain open after birth. At this tume the shunt would be left to right, that would cause pulmonary congestion, and systemic hypoperfusion.
Ibuprofen is the treatment of choice for PDA in preterm infants. Yet, ibuprofen is not effective after two weeks of age. Moreover, there are situations that prevent treatment with ibuprofen, such as thrombocytopenia or renal failure. Surgical closure of arterial duct is an alternative treatment, if ibuprofen is contraindicated, or if it fails.
Lastly, there was a report that acetaminophen may have a role in pharmacological closure of PDA in preterm infants.
The investigators conducted this open label non randomized and non control study to try to support that report.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| No known PDA | No intervention | –For all infants, we do echo cardiogram study only if they are suspected of having PDA, due to sings and symptoms. Hence, we do not do echo cardiogram study to most of the infants. |
| Ibuprofen | Active comparator | Drug: IbuprofenIf there is a PDA, that should be treated, and the infant is less than 2 weeks of age, we use ibuprofen, as this is the gold standard in literature. |
| Surgical closure of PDA | Active comparator | Procedure: Closure of PDAInfants with symptomatic PDA, who had to be treated, but could not be treated by ibuprofen, either due to age (> 2 weeks) or due ibuprofen contraindications (thrombocytopenia or renal failure), whose could not be treated by paracetamol (either because of parents' refuse or because they were on nothing per os protocol due to other disease), for whom surgery was the treatment of choice to close the arterial duct. |
| Paracetamol | Experimental | Drug: ParacetamolInfants with symptomatic PDA who could not be treated with ibuprofen, and their parents agreed and they could be treated with paracetamol. |
| DA closed spontaneously | No intervention | –Infants with PDA, who did not get any treatment for it, and the duct was closed spontaneously. |
Who may qualify
- Ages
- Up to 4 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- Preterm infants with symptomatic PDA who could not be treated with ibuprofen
Key exclusion criteria (1 listed)
- None
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 |
|---|---|---|
| ParacetamolAlso: AcetaminophenPer gavage paracetamol 15 mg/kg every 6 hours, for up to 7 days. | Drug | Paracetamol |
| IbuprofenPer Gavage ibuprofen 10mg/kg x 3/d for up to 5 days Gold standard per literature | Drug | Ibuprofen |
| Closure of PDAOpen surgery for closure of PDA | Procedure or surgery | Surgical closure of PDA |
Primary outcome
Closure of arterial duct - yes / No
Time frame: 1 week
Echo-cardiogram that will give exact answer to the question: "was the arterial duct closed"?
1 secondary outcome
Need for surgical closure of arterial duct
Time frame: 1 week
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 6 Aug 2019.
- Background: PubMed 22065264Hammerman C, Bin-Nun A, Markovitch E, Schimmel MS, Kaplan M, Fink D. Ductal closure with paracetamol: a surprising new approach to patent ductus arteriosus treatment. Pediatrics. 2011 Dec;128(6):e1618-21. doi: 10.1542/peds.2011-0359. Epub 2011 Nov 7.
- Background: PubMed 22414884Hammerman C, Bin-Nun A, Kaplan M. Managing the patent ductus arteriosus in the premature neonate: a new look at what we thought we knew. Semin Perinatol. 2012 Apr;36(2):130-8. doi: 10.1053/j.semperi.2011.09.023.
- Background: PubMed 22611117Oncel MY, Yurttutan S, Uras N, Altug N, Ozdemir R, Ekmen S, Erdeve O, Dilmen U. An alternative drug (paracetamol) in the management of patent ductus arteriosus in ibuprofen-resistant or contraindicated preterm infants. Arch Dis Child Fetal Neonatal Ed. 2013 Jan;98(1):F94. doi: 10.1136/archdischild-2012-302044. Epub 2012 May 18. No abstract available.
- Background: PubMed 3884385Peterson RG. Consequences associated with nonnarcotic analgesics in the fetus and newborn. Fed Proc. 1985 Apr;44(7):2309-13.
- Background: PubMed 7469626Rudolph AM. Effects of aspirin and acetaminophen in pregnancy and in the newborn. Arch Intern Med. 1981 Feb 23;141(3 Spec No):358-63. doi: 10.1001/archinte.141.3.358.
- Background: PubMed 12521476Simbi KA, Secchieri S, Rinaldo M, Demi M, Zanardo V. In utero ductal closure following near-term maternal self-medication with nimesulide and acetaminophen. J Obstet Gynaecol. 2002 Jul;22(4):440-1. doi: 10.1080/01443610220141489. No abstract available.
- Background: PubMed 17125127Weintraub A, Mankuta D. Dipyrone-induced oligohydramnios and ductus arteriosus restriction. Isr Med Assoc J. 2006 Oct;8(10):722-3. No abstract available.
- Background: PubMed 22814005Burdan F, Staroslawska E, Szumilo J. Prenatal tolerability of acetaminophen and other over-the-counter non-selective cyclooxygenase inhibitors. Pharmacol Rep. 2012;64(3):521-7. doi: 10.1016/s1734-1140(12)70847-2.
- 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.
Erez Nadir, MD principal investigator
Hillel Yaffe medical center, Hadera, Israel
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Paracetamol, Ibuprofen and Closure of PDA in people with PDA, run by Hillel Yaffe Medical Center at 1 site in Israel.
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 6 Aug 2019. 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 Israel. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Closure of arterial duct - yes / No (time frame: 1 week). 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 NCT01755728, which also lists 8 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 6 Aug 2019; AzTrials last refreshed its copy on 7 Nov 2026.