Patent Ductus ArteriosusPhase 2NCT02819414
Paracetamol Treatment of the Borderline Significant PDA
A Phase 2 study testing Paracetamol drops in people with Patent Ductus Arteriosus, run by Shaare Zedek Medical Center at 1 site in Israel.
Trial summary
The therapeutic approach to the patent ductus arteriosus (PDA) in the premature neonate remains controversial. Currently it is generally accepted to treat only hemodynamically significant PDAs. Read more about this study
- Who is it for?
- Ages 3 to 6 days
- Conditions the study is for
- Patent Ductus Arteriosus
- What is being tested?
- Paracetamol drops
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteIsrael
- Study dates
- Jun 2016to Jan 2019
- Phase
- Phase 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 3 to 6 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Preterm neonates < 30 weeks' gestational age PDA of borderline significance
Who cannot join
- Infants not deemed likely to survive more than one week Infants with congenital heart malformations Infants with pulmonary hypertension and right to left ductal shunting
Trial locations and contacts
1 site in 1 country.
About this study
Official title: TIME TO RE-EVALUATE THE KINDER GENTLER APPROACH TO PATENT DUCTUS ARTERIOSUS (PDA) IN THE PRETERM NEONATE
The therapeutic approach to the patent ductus arteriosus (PDA) in the premature neonate remains controversial. Currently it is generally accepted to treat only hemodynamically significant PDAs. The current investigation aims to study the effect of treatment on PDAs of borderline significance via a prospective, randomized controlled trial of paracetamol in this group.
Read the detailed description
In the neonatal intensive care unit of the Shaare Zedek Medical Center, preterm babies <30 wks. GA, are studied echocardiographically on day of life 3-4. Pending parental informed consent, those diagnosed with a PDA of borderline significance will be randomized to receive either paracetamol or placebo for three days, followed by a repeat echocardiogram. If the PDA remains of borderline significance, the treatment will be continued for an additional 4 days (1 week total). Paracetamol levels and liver functions will be assessed after the third day. Babies will be followed until discharge for subsequent PDA pathology; respiratory distress and chronic lung disease [CLD]; necrotizing enterocolitis [NEC]; retinopathy of prematurity [ROP].
The investigators' primary goal is to demonstrate a decrease in the composite outcome of death or severe morbidity chronic lung disease [CLD], as shown by decreased time on supplemental oxygen and assisted ventilation.
Secondary goals:
- To demonstrate a decrease in subsequently diagnosed hs PDA, including
- Decrease in the need for subsequent therapy for PDA closure
- Decrease in surgical PDA ligations
- To demonstrate a decrease in necrotizing enterocolitis (NEC) and/or ROP with treatment.
- To demonstrate no adverse effect on blood flow in anterior cerebral, superior mesenteric and renal arteries.
- Conditions
- Patent Ductus Arteriosus
- Being tested
- Paracetamol drops, Placebo
- Medical subject headings
- Ductus Arteriosus, Patent
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Paracetamol dropsDrug
Also called Novimol
15 mg/kg/dose x 4/day diluted 1:15 yielding dose of 2.25 ml/kg/dose to be given for three days
PlaceboOther
2.25 ml/kg/dose x 4/day of sterile water to be given for three days
| Study group | Role | What they receive |
|---|---|---|
| Control Group | Placebo comparator | Treatment with placebo at a volume of 2.25 cc/kg/dose x 4/day to be given with feeds, or in place of feed when baby is receiving <2 cc/kg/feed. Receives: Other: Placebo |
| Treatment Group | Active comparator | Treatment with paracetamol drops at 15 mg/kg/dose x 4/day. Drops will be diluted 1:15 in order to reduce osmolality. This will yield a dose of 2.25 ml/kg/dose, to be given with feeds, or in place of feed when baby is receiving <2 cc/kg/feed. Receives: Drug: Paracetamol drops |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite outcome of death or severe morbidity chronic lung disease [CLD]
Chronic lung disease will be assessed by time on supplemental oxygen and assisted ventilation.
Measured: Day of life 3 until 40 weeks post-conception
Secondary outcomes (2)
Subsequently diagnosed hs PDA
Will be assessed by subsequent need for medical or surgical intervention for closure of PDA
Measured: Completion of study intervention until 40 weeks post-conception
Subsequent incidence of necrotizing enterocolitis (NEC) and/or retinopathy of prematurity (ROP)
Study infants will be followed clinically and any occurrence of NEC or ROP will be recorded with its level of significance (Bell staging for NEC and Stage of ROP)
Measured: Completion of study intervention until 40 weeks post-conception
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2016 (estimated)
- Study startJun 2016
- Primary completionJun 2018 (estimated)
- Study completionJan 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Patent Ductus ArteriosusStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shaare Zedek Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Cathy Hammerman, Shaare Zedek Medical Center
- Investigators
- Cathy Hammerman, MD, Principal investigator, Shaare Zedek Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02819414
- Sponsor's protocol ID
- 0174-16-SZMC
- Status last verified
- Jul 2016
- First submitted
- 28 Jun 2016
- Last updated
- 6 Jul 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Terrin G, Conte F, Oncel MY, Scipione A, McNamara PJ, Simons S, Sinha R, Erdeve O, Tekgunduz KS, Dogan M, Kessel I, Hammerman C, Nadir E, Yurttutan S, Jasani B, Alan S, Manguso F, De Curtis M. Paracetamol for the treatment of patent ductus arteriosus in preterm neonates: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2016 Mar;101(2):F127-36. doi: 10.1136/archdischild-2014-307312. Epub 2015 Aug 17.
PubMed 26283668Hammerman 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 22065264
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TIME TO RE-EVALUATE THE KINDER GENTLER APPROACH TO PATENT DUCTUS ARTERIOSUS (PDA) IN THE PRETERM NEONATE
- ClinicalTrials.gov ID
- NCT02819414
- Acronym / sponsor ID
- 0174-16-SZMC
- Conditions
- Patent Ductus Arteriosus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Shaare Zedek Medical CenterUniversity, hospital or other
- Study start
- Jun 2016
- Primary completion
- Jun 2018 (estimated)
- Study completion
- Jan 2019 (estimated)
- First posted
- 30 Jun 2016 (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.
The therapeutic approach to the patent ductus arteriosus (PDA) in the premature neonate remains controversial. Currently it is generally accepted to treat only hemodynamically significant PDAs. The current investigation aims to study the effect of treatment on PDAs of borderline significance via a prospective, randomized controlled trial of paracetamol in this group.
Detailed description
In the neonatal intensive care unit of the Shaare Zedek Medical Center, preterm babies <30 wks. GA, are studied echocardiographically on day of life 3-4. Pending parental informed consent, those diagnosed with a PDA of borderline significance will be randomized to receive either paracetamol or placebo for three days, followed by a repeat echocardiogram. If the PDA remains of borderline significance, the treatment will be continued for an additional 4 days (1 week total). Paracetamol levels and liver functions will be assessed after the third day. Babies will be followed until discharge for subsequent PDA pathology; respiratory distress and chronic lung disease [CLD]; necrotizing enterocolitis [NEC]; retinopathy of prematurity [ROP].
The investigators' primary goal is to demonstrate a decrease in the composite outcome of death or severe morbidity chronic lung disease [CLD], as shown by decreased time on supplemental oxygen and assisted ventilation.
Secondary goals:
- To demonstrate a decrease in subsequently diagnosed hs PDA, including
- Decrease in the need for subsequent therapy for PDA closure
- Decrease in surgical PDA ligations
- To demonstrate a decrease in necrotizing enterocolitis (NEC) and/or ROP with treatment.
- To demonstrate no adverse effect on blood flow in anterior cerebral, superior mesenteric and renal arteries.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control Group | Placebo comparator | Other: PlaceboTreatment with placebo at a volume of 2.25 cc/kg/dose x 4/day to be given with feeds, or in place of feed when baby is receiving <2 cc/kg/feed. |
| Treatment Group | Active comparator | Drug: Paracetamol dropsTreatment with paracetamol drops at 15 mg/kg/dose x 4/day. Drops will be diluted 1:15 in order to reduce osmolality. This will yield a dose of 2.25 ml/kg/dose, to be given with feeds, or in place of feed when baby is receiving <2 cc/kg/feed. |
Who may qualify
- Ages
- 3 to 6 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- Preterm neonates < 30 weeks' gestational age PDA of borderline significance
Key exclusion criteria (1 listed)
- Infants not deemed likely to survive more than one week Infants with congenital heart malformations Infants with pulmonary hypertension and right to left ductal shunting
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 dropsAlso: Novimol15 mg/kg/dose x 4/day diluted 1:15 yielding dose of 2.25 ml/kg/dose to be given for three days | Drug | Treatment Group |
| Placebo2.25 ml/kg/dose x 4/day of sterile water to be given for three days | Other | Control Group |
Primary outcome
Composite outcome of death or severe morbidity chronic lung disease [CLD]
Time frame: Day of life 3 until 40 weeks post-conception
Chronic lung disease will be assessed by time on supplemental oxygen and assisted ventilation.
2 secondary outcomes
Subsequently diagnosed hs PDA
Time frame: Completion of study intervention until 40 weeks post-conception
Subsequent incidence of necrotizing enterocolitis (NEC) and/or retinopathy of prematurity (ROP)
Time frame: Completion of study intervention until 40 weeks post-conception
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2016.
- Results publication: PubMed 26283668Terrin G, Conte F, Oncel MY, Scipione A, McNamara PJ, Simons S, Sinha R, Erdeve O, Tekgunduz KS, Dogan M, Kessel I, Hammerman C, Nadir E, Yurttutan S, Jasani B, Alan S, Manguso F, De Curtis M. Paracetamol for the treatment of patent ductus arteriosus in preterm neonates: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2016 Mar;101(2):F127-36. doi: 10.1136/archdischild-2014-307312. Epub 2015 Aug 17.
- Results publication: 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.
- 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.
Cathy Hammerman, MD principal investigator
Shaare Zedek Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Paracetamol drops in people with Patent Ductus Arteriosus, run by Shaare Zedek 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: status not confirmed, as of the sponsor's last update on 6 Jul 2016. 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. 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 phase mean?
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?
Results are not available in the source record.
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?
Composite outcome of death or severe morbidity chronic lung disease [CLD] (time frame: Day of life 3 until 40 weeks post-conception). 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 NCT02819414, which also lists 2 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 Jul 2016.