Fetal HypoxiaPhase 3NCT00189007

Antenatal Allopurinol During Fetal Hypoxia

A Phase 3 study testing Allopurinol sodium and Mannitol in people with Fetal Hypoxia and Reperfusion Injury, run by UMC Utrecht at 11 sites in Netherlands.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record

Search all trials

Trial summary

Who is it for?: Any age
Conditions the study is for: Fetal Hypoxia, Reperfusion Injury
What is being tested?: Allopurinol sodium and Mannitol
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 222 participants
Where: 11 sitesNetherlands
Study dates: Oct 2009to Dec 2016
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 Any age
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

Gestational age of 36 weeks or more
Non-reassuring CTG, significant events on the STAN-monitor AND/OR FBS < 7.20

Who cannot join

Chromosomal abnormalities

Trial locations and contacts

11 sites in 1 country.

City, postcode or hospital

11 sites in 1 country

Netherlands11 sites

Jeroen Bosch Hospital
's-Hertogenbosch
AMC
Amsterdam
VUmc
Amsterdam
Gelre hospitals
Apeldoorn
Groene Hart Hospital
Gouda
UMCG
Groningen
LUMC
Leiden
Maastricht University Medical Center
Maastricht
Wilhelmina Children's Hospital/UMC Utrecht
Utrecht, Utrecht, 3508AB
Diakonessenhuis
Utrecht
Maxima Medical Center
Veldhoven

Other trials in Netherlands

About this study

Official title: Does Antenatal Allopurinol Administration Reduce Post-hypoxic-ischemic Reperfusion Damage During Fetal Hypoxia in the Newborn?

A former study (submitted) in 32 severely asphyxiated infants participating in a randomized double blind study, in which early postnatal allopurinol or a placebo (within 4 hours after birth) was administered to reduce free radical formation and consequently reperfusion/reoxygenation injury to the newborn brain, showed an unaltered high mortality and no clinically relevant improvement in morbidity in infants treated with allopurinol. It was hypothesized that postnatal allopurinol treatment started too late to reduce reperfusion-induced free radical surge and that initiating allopurinol treatment of the fetus with (imminent) hypoxia already via the mother during labor will be more effective to reduce free radical-induced post-asphyxial brain damage.

Conditions: Fetal Hypoxia, Reperfusion Injury
Being tested: Allopurinol sodium, Mannitol
Keywords: allopurinol, neuroprotection, reperfusion injury, fetal hypoxia, post hypoxic-ischemic reperfusion damage
Medical subject headings: Fetal Hypoxia, Reperfusion Injury

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Allopurinol sodiumDrug
Also called Acepurin
Allopurinol sodium 500 mg / 50 mL, intravenously, single dose
MannitolDrug
Mannitol 500 mg/50 mL water for injection, intravenously, single dose

Study groups in NCT00189007
Study group	Role	What they receive
Allopurinol	Experimental	500 mg allopurinol/ 50 mL water for injection intravenously Receives: Drug: Allopurinol sodium
Placebo	Placebo comparator	500 mg mannitol/50 mL water for injection intravenously Receives: Drug: Mannitol

What is being measured

The primary outcome is the main question the study is designed to answer.

Free radical production and markers of neuronal damage
Measured: Up to 24 hours postpartum

Secondary outcomes (3)

Developmental outcome
Measured: Up to 5 years of age
Mortality
Measured: Up to 28 days postpartum
Severe composite morbidity
Measured: Up to 28 days postpartum

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2009Dec 2016

First posted16 Sep 2005 (estimated)
Study startOct 2009
Primary completionDec 2011
Study completionDec 2016 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (5)Papers the sponsor has linked to this study.
Other trials for Fetal HypoxiaStudies of the same condition, open and under way.
More trials run by UMC UtrechtThe sponsor's other registered studies.
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: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 222 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00189007
Sponsor's protocol ID: ZonMw 170991001
Other IDs: ALLO-trial, 2006-005796-18, 170991001, NTR-1383, NL26516.000.09
Status last verified: Mar 2012
First submitted: 11 Sep 2005
Last updated: 29 Mar 2012
Results posted: No
Data monitoring committee: Yes

Publications

Kaandorp JJ, Benders MJ, Rademaker CM, Torrance HL, Oudijk MA, de Haan TR, Bloemenkamp KW, Rijken M, van Pampus MG, Bos AF, Porath MM, Oetomo SB, Willekes C, Gavilanes AW, Wouters MG, van Elburg RM, Huisjes AJ, Bakker SC, van Meir CA, von Lindern J, Boon J, de Boer IP, Rijnders RJ, Jacobs CJ, Uiterwaal CS, Mol BW, Visser GH, van Bel F, Derks JB. Antenatal allopurinol for reduction of birth asphyxia induced brain damage (ALLO-Trial); a randomized double blind placebo controlled multicenter study. BMC Pregnancy Childbirth. 2010 Feb 18;10:8. doi: 10.1186/1471-2393-10-8.
PubMed 20167117
Klumper J, Kaandorp JJ, Schuit E, Groenendaal F, Koopman-Esseboom C, Mulder EJH, Van Bel F, Benders MJNL, Mol BWJ, van Elburg RM, Bos AF, Derks JB; ALLO-trial study group. Behavioral and neurodevelopmental outcome of children after maternal allopurinol administration during suspected fetal hypoxia: 5-year follow up of the ALLO-trial. PLoS One. 2018 Aug 23;13(8):e0201063. doi: 10.1371/journal.pone.0201063. eCollection 2018.
PubMed 30138355
Kaandorp JJ, Benders MJ, Schuit E, Rademaker CM, Oudijk MA, Porath MM, Oetomo SB, Wouters MG, van Elburg RM, Franssen MT, Bos AF, de Haan TR, Boon J, de Boer IP, Rijnders RJ, Jacobs CJ, Scheepers LH, Gavilanes DA, Bloemenkamp KW, Rijken M, van Meir CA, von Lindern JS, Huisjes AJ, Bakker SC, Mol BW, Visser GH, Van Bel F, Derks JB. Maternal allopurinol administration during suspected fetal hypoxia: a novel neuroprotective intervention? A multicentre randomised placebo controlled trial. Arch Dis Child Fetal Neonatal Ed. 2015 May;100(3):F216-23. doi: 10.1136/archdischild-2014-306769. Epub 2014 Dec 15.
PubMed 25512466
Kaandorp JJ, van den Broek MP, Benders MJ, Oudijk MA, Porath MM, Bambang Oetomo S, Wouters MG, van Elburg R, Franssen MT, Bos AF, Mol BW, Visser GH, van Bel F, Rademaker CM, Derks JB; ALLO-trial Study Group. Rapid target allopurinol concentrations in the hypoxic fetus after maternal administration during labour. Arch Dis Child Fetal Neonatal Ed. 2014 Mar;99(2):F144-8. doi: 10.1136/archdischild-2013-304876. Epub 2013 Dec 18.
PubMed 24352085
Torrance HL, Benders MJ, Derks JB, Rademaker CM, Bos AF, Van Den Berg P, Longini M, Buonocore G, Venegas M, Baquero H, Visser GH, Van Bel F. Maternal allopurinol during fetal hypoxia lowers cord blood levels of the brain injury marker S-100B. Pediatrics. 2009 Jul;124(1):350-7. doi: 10.1542/peds.2008-2228.
PubMed 19564319

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Sustained Cord Circulation at Emergency Cesarean Section
Asphyxia Neonatorum, Fetal Hypoxia
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Amnioinfusion for Chorioamnionitis: Targeting Neonatal Brain Injury Biomarkers
Chorioamnionitis Affecting Fetus or Newborn, Amnioinfusion
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Post Market Clinical Follow-up to Assess the Portable Nitric Oxide Generation and Delivery System (INOwill N200) for the Treatment of Neonatal Hypoxic Respiratory Failure Complicated by Pulmonary Hypertension
Persistent Pulmonary Hypertension of the Newborn, Hypoxic Respiratory Failure
Not yet recruitingObservational study
Gemini Flash 3.6 Versus Human Observers for FIGO-Based Interpretation of Intrapartum Cardiotocography
Fetal Hypoxia, Fetal Distress
Not yet recruitingObservational study
Evaluation of Neonatal Acute Hypoxia at Delivery Using Fetal Physiology and Eucapnic pH Assessment
Neonatal Acidemia and Hypoxia

All Fetal Hypoxia trials

Study at a glance

From the registry record, last updated by the sponsor on 29 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Does Antenatal Allopurinol Administration Reduce Post-hypoxic-ischemic Reperfusion Damage During Fetal Hypoxia in the Newborn?
ClinicalTrials.gov ID: NCT00189007
Acronym / sponsor ID: ZonMw 170991001
Conditions: Fetal Hypoxia, Reperfusion Injury
Keywords: allopurinol, neuroprotection, reperfusion injury, fetal hypoxia, post hypoxic-ischemic reperfusion damage
Phase: Phase 3
Study type: Interventional
Recruitment status: Unknown status
Enrolment: 222 participants (actual)
Lead sponsor: UMC UtrechtUniversity, hospital or other
Collaborators: ZonMw: The Netherlands Organisation for Health Research and Development
Study start: Oct 2009
Primary completion: Dec 2011 (actual)
Study completion: Dec 2016 (estimated)
First posted: 16 Sep 2005 (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.

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
Allopurinol	Experimental	Drug: Allopurinol sodium500 mg allopurinol/ 50 mL water for injection intravenously
Placebo	Placebo comparator	Drug: Mannitol500 mg mannitol/50 mL water for injection intravenously

Who may qualify

Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (2 listed)

Gestational age of 36 weeks or more
Non-reassuring CTG, significant events on the STAN-monitor AND/OR FBS < 7.20

Key exclusion criteria (1 listed)

Chromosomal abnormalities

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
Allopurinol sodiumAlso: AcepurinAllopurinol sodium 500 mg / 50 mL, intravenously, single dose	Drug	Allopurinol
MannitolMannitol 500 mg/50 mL water for injection, intravenously, single dose	Drug	Placebo

Primary outcome

Free radical production and markers of neuronal damage
Time frame: Up to 24 hours postpartum

3 secondary outcomes

Developmental outcome
Time frame: Up to 5 years of age
Mortality
Time frame: Up to 28 days postpartum
Severe composite morbidity
Time frame: Up to 28 days postpartum

Results and safety

Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2012.
Background: PubMed 20167117Kaandorp JJ, Benders MJ, Rademaker CM, Torrance HL, Oudijk MA, de Haan TR, Bloemenkamp KW, Rijken M, van Pampus MG, Bos AF, Porath MM, Oetomo SB, Willekes C, Gavilanes AW, Wouters MG, van Elburg RM, Huisjes AJ, Bakker SC, van Meir CA, von Lindern J, Boon J, de Boer IP, Rijnders RJ, Jacobs CJ, Uiterwaal CS, Mol BW, Visser GH, van Bel F, Derks JB. Antenatal allopurinol for reduction of birth asphyxia induced brain damage (ALLO-Trial); a randomized double blind placebo controlled multicenter study. BMC Pregnancy Childbirth. 2010 Feb 18;10:8. doi: 10.1186/1471-2393-10-8.
Derived from this study: PubMed 30138355Klumper J, Kaandorp JJ, Schuit E, Groenendaal F, Koopman-Esseboom C, Mulder EJH, Van Bel F, Benders MJNL, Mol BWJ, van Elburg RM, Bos AF, Derks JB; ALLO-trial study group. Behavioral and neurodevelopmental outcome of children after maternal allopurinol administration during suspected fetal hypoxia: 5-year follow up of the ALLO-trial. PLoS One. 2018 Aug 23;13(8):e0201063. doi: 10.1371/journal.pone.0201063. eCollection 2018.
Derived from this study: PubMed 25512466Kaandorp JJ, Benders MJ, Schuit E, Rademaker CM, Oudijk MA, Porath MM, Oetomo SB, Wouters MG, van Elburg RM, Franssen MT, Bos AF, de Haan TR, Boon J, de Boer IP, Rijnders RJ, Jacobs CJ, Scheepers LH, Gavilanes DA, Bloemenkamp KW, Rijken M, van Meir CA, von Lindern JS, Huisjes AJ, Bakker SC, Mol BW, Visser GH, Van Bel F, Derks JB. Maternal allopurinol administration during suspected fetal hypoxia: a novel neuroprotective intervention? A multicentre randomised placebo controlled trial. Arch Dis Child Fetal Neonatal Ed. 2015 May;100(3):F216-23. doi: 10.1136/archdischild-2014-306769. Epub 2014 Dec 15.
Derived from this study: PubMed 24352085Kaandorp JJ, van den Broek MP, Benders MJ, Oudijk MA, Porath MM, Bambang Oetomo S, Wouters MG, van Elburg R, Franssen MT, Bos AF, Mol BW, Visser GH, van Bel F, Rademaker CM, Derks JB; ALLO-trial Study Group. Rapid target allopurinol concentrations in the hypoxic fetus after maternal administration during labour. Arch Dis Child Fetal Neonatal Ed. 2014 Mar;99(2):F144-8. doi: 10.1136/archdischild-2013-304876. Epub 2013 Dec 18.
Derived from this study: PubMed 19564319Torrance HL, Benders MJ, Derks JB, Rademaker CM, Bos AF, Van Den Berg P, Longini M, Buonocore G, Venegas M, Baquero H, Visser GH, Van Bel F. Maternal allopurinol during fetal hypoxia lowers cord blood levels of the brain injury marker S-100B. Pediatrics. 2009 Jul;124(1):350-7. doi: 10.1542/peds.2008-2228.

Related trials for Fetal Hypoxia

Recruiting
Sustained Cord Circulation at Emergency Cesarean Section
Asphyxia Neonatorum, Fetal Hypoxia
Recruiting
Amnioinfusion for Chorioamnionitis: Targeting Neonatal Brain Injury Biomarkers
Chorioamnionitis Affecting Fetus or Newborn, Amnioinfusion
Not yet recruitingObservational study
Post Market Clinical Follow-up to Assess the Portable Nitric Oxide Generation and Delivery System (INOwill N200) for the Treatment of Neonatal Hypoxic Respiratory Failure Complicated by Pulmonary Hypertension
Persistent Pulmonary Hypertension of the Newborn, Hypoxic Respiratory Failure
Not yet recruitingObservational study
Gemini Flash 3.6 Versus Human Observers for FIGO-Based Interpretation of Intrapartum Cardiotocography
Fetal Hypoxia, Fetal Distress
Not yet recruitingObservational study
Evaluation of Neonatal Acute Hypoxia at Delivery Using Fetal Physiology and Eucapnic pH Assessment
Neonatal Acidemia and Hypoxia

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.

Frank van Bel, Prof MD PhD study director

Wilhelmina Children's Hospital/UMC Utrecht

Manon JN Benders, MD, PhD principal investigator

UMC Utrecht

Jan B Derks, MD, PhD principal investigator

UMC Utrecht

11 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Allopurinol sodium and Mannitol in people with Fetal Hypoxia and Reperfusion Injury, run by UMC Utrecht at 11 sites in Netherlands.

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 2 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 29 Mar 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in Netherlands. 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 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?

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?

Free radical production and markers of neuronal damage (time frame: Up to 24 hours postpartum). 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 NCT00189007, which also lists 5 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 29 Mar 2012.