Hypoxic Ischaemic Encephalopathy (HIE)NCT07763145
Effect of Citicoline on Neurological Severity Score and Cerebral Doppler Resistive Index in Neonatal Hypoxic Ischemic Encephalopathy
A study testing Citicoline and Standard medical treatment in people with Hypoxic Ischaemic Encephalopathy (HIE), run by Khyber Girls Medical College at 1 site in Pakistan.
Trial summary
To determine the efficacy of citicoline in improving cerebral blood flow parameters and neurological status among neonates with hypoxic-ischemic encephalopathy using Doppler resistive index and Sarnat-Sarnat score after 72 hours of therapy. Read more about this study
- Who is it for?
- Ages 0 to 24 hours
- Conditions the study is for
- Hypoxic Ischaemic Encephalopathy (HIE)
- What is being tested?
- Citicoline and Standard medical treatment
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 86 participants
- Where
- 1 sitePakistan
- Study dates
- 1 Sep 2026to 30 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 0 to 24 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- All inborn neonates diagnosed with APGAR score (Table 2) less then 8/10 at 5 min of life presenting to the emergency room within the first day of life.
- Outborn babies admitted in the last 24 hours with history or clinical features of perinatal asphyxia.
Who cannot join
- Neonates who have received therapeutic hypothermia
- Neonates with congenital, developmental or chromosomal malformations
- Significant antenatal risk factors leading to early-onset sepsis\DIC or CNS depression unrelated to asphyxia
- Preterm neonates <35 weeks
- No consent could be obtained
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Pakistan1 site
Hayatabad Medical Complex
Peshawar, KPK, 25000
Romisa Rehman, FCPS, MRCPCH, 00923219059305, measa_awan@hotmail.com
Romisa Rehman, MBBS, FCPS, MRCPCH
About this study
Official title: Effect of Citicoline on Neurological Severity Score and Cerebral Doppler Resistive Index in Neonatal Hypoxic Ischemic Encephalopathy: A Randomized Control Trial
To determine the efficacy of citicoline in improving cerebral blood flow parameters and neurological status among neonates with hypoxic-ischemic encephalopathy using Doppler resistive index and Sarnat-Sarnat score after 72 hours of therapy.
Read the detailed description
Hypoxic-ischemic encephalopathy (HIE) is a leading cause of neonatal brain injury worldwide. In the developed world, the incidence is estimated at up to 8 per 1,000 live births, while in developing countries, estimates are as high as 26 per 1,000 live births. Approximately 20-30% of infants with HIE die in the neonatal period, and 33-50% of survivors are left with permanent neurodevelopmental abnormalities.1 HIE can be classified into mild (Stage I), moderate (Stage II), and severe (Stage III) based on the Sarnat and Sarnat staging system(Table 1), with stage II and III being associated with the highest morbidity and mortality.
Therapeutic hypothermia remains the standard therapy for HIE. However, its availability, high costs, need for specialized equipment and monitoring limit its use in developing countries like Pakistan, therefore alternative neuroprotective agents are used however there is still no consensus regarding which agent is the most effective. Citicoline (cytidine diphosphate choline) has demonstrated several neuroprotective mechanisms. It helps preserve neuronal membrane integrity by maintaining phospholipids while decreasing phospholipase A2 activity and oxidative damage.2 It also enhances phosphatidylcholine synthesis and promotes glutathione production, thereby decreasing free-radical-mediated neuronal injury. Experimental studies further suggest neuroprotective roles of citicoline as it modulates excitotoxicity by decreasing glutamate levels.3,4 These combined effects may contribute to improved neuronal survival and recovery after hypoxic-ischemic insults. Long term effects have been studied however no study evaluates short term improvement from therapy.
Resistive Index is a parameter assessed on cranial doppler ultrasonography, it is difference between peak systolic and end diastolic pressures in the anterior cerebral arteries, normal value is 0.68-0.72 5it demonstrates cerebral blood flow changes due to hypoxia, lower values have been associated with worse neurological outcome.5 RI has been studied in comparison to MRI and also its changes pre and post therapeutic hypothermia, and has been found to be useful tool6,7. American Academy of Neurology and Practice Committee of the Child Neurology Society recommends RI and end diastolic flow velocity (EDFV) in the anterior cerebral artery to assess cerebral perfusion and early prediction of outcome.8 This study is therefore designed to assess the effect of citicoline on cerebral resistive index and neurological improvement using Sarnat-Sarnat scoring after 3 days of treatment in neonates with hypoxic-ischemic encephalopathy. The findings may contribute to establishing evidence for adjunctive therapeutic strategies aimed at reducing neurological morbidity in affected neonates. Despite its clinical use in some centers, there is limited published evidence regarding the efficacy of citicoline in neonates with HIE.
- Conditions
- Hypoxic Ischaemic Encephalopathy (HIE)
- Being tested
- Citicoline, Standard medical treatment
- Medical subject headings
- Hypoxia-Ischemia, Brain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CiticolineDrug
This group will receive drug and standard care
Standard medical treatmentOther
This group will receive only standard care
| Study group | Role | What they receive |
|---|---|---|
| Intervention Group | Experimental | This will receive medicine citicoline with standard care Receives: Drug: Citicoline |
| Control group | Placebo comparator | Only receive standard care Receives: Other: Standard medical treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sarnat and Sarnat scoring
Measured: enrollment to 72 hours
Cerebral Resistive Index
Measured: Enrollment to 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2026
- Study start1 Sep 2026 (estimated)
- Primary completion30 Dec 2026 (estimated)
- Study completion30 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Hypoxic Ischaemic Encephalopathy (HIE)Studies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 86 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Khyber Girls Medical College
- Sponsor type
- University, hospital or other
- Collaborators
- Hayatabad Medical Complex
- Responsible party
- Sponsor
- Investigators
- Romisa Rehman, Principal investigator, Hyatabad Medical Complex
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07763145
- Sponsor's protocol ID
- ASRD 411
- Status last verified
- Aug 2026
- First submitted
- 8 Aug 2026
- Last updated
- 24 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Salamah A, El Amrousy D, Elsheikh M, Mehrez M. Citicoline in hypoxic ischemic encephalopathy in neonates: a randomized controlled trial. Ital J Pediatr. 2023 May 12;49(1):55. doi: 10.1186/s13052-023-01452-5.
PubMed 37173784Edwards AD, Brocklehurst P, Gunn AJ, Halliday H, Juszczak E, Levene M, Strohm B, Thoresen M, Whitelaw A, Azzopardi D. Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: synthesis and meta-analysis of trial data. BMJ. 2010 Feb 9;340:c363. doi: 10.1136/bmj.c363.
PubMed 20144981Gerner GJ, Burton VJ, Poretti A, Bosemani T, Cristofalo E, Tekes A, Seyfert D, Parkinson C, Leppert M, Allen M, Huisman TA, Northington FJ, Johnston MV. Transfontanellar duplex brain ultrasonography resistive indices as a prognostic tool in neonatal hypoxic-ischemic encephalopathy before and after treatment with therapeutic hypothermia. J Perinatol. 2016 Mar;36(3):202-6. doi: 10.1038/jp.2015.169. Epub 2015 Nov 26.
PubMed 26609871Snyder EJ, Perin J, Chavez-Valdez R, Northington FJ, Lee JK, Tekes A. Head Ultrasound Resistive Indices Are Associated With Brain Injury on Diffusion Tensor Imaging Magnetic Resonance Imaging in Neonates With Hypoxic-Ischemic Encephalopathy. J Comput Assist Tomogr. 2020 Sep/Oct;44(5):687-691. doi: 10.1097/RCT.0000000000001069.
PubMed 32842070Hurtado O, Moro MA, Cardenas A, Sanchez V, Fernandez-Tome P, Leza JC, Lorenzo P, Secades JJ, Lozano R, Davalos A, Castillo J, Lizasoain I. Neuroprotection afforded by prior citicoline administration in experimental brain ischemia: effects on glutamate transport. Neurobiol Dis. 2005 Mar;18(2):336-45. doi: 10.1016/j.nbd.2004.10.006.
PubMed 15686962Adibhatla RM, Hatcher JF, Dempsey RJ. Citicoline: neuroprotective mechanisms in cerebral ischemia. J Neurochem. 2002 Jan;80(1):12-23. doi: 10.1046/j.0022-3042.2001.00697.x.
PubMed 11796739Cohen SS, Sprecher AJ, Acharya KK. Hypoxic-ischemic encephalopathy. In: Kliegman RM, St. Geme JW, Blum NJ, Tasker RC, Wilson KM, Schuh AM, Mack CL, editors. Nelson Textbook of Pediatrics. 22nd ed. Vol 1. Philadelphia: Elsevier; 2024. p. 1062.
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Citicoline on Neurological Severity Score and Cerebral Doppler Resistive Index in Neonatal Hypoxic Ischemic Encephalopathy: A Randomized Control Trial
- ClinicalTrials.gov ID
- NCT07763145
- Acronym / sponsor ID
- ASRD 411
- Conditions
- Hypoxic Ischaemic Encephalopathy (HIE)
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 86 participants (estimated)
- Lead sponsor
- Khyber Girls Medical CollegeUniversity, hospital or other
- Collaborators
- Hayatabad Medical Complex
- Study start
- 1 Sep 2026 (estimated)
- Primary completion
- 30 Dec 2026 (estimated)
- Study completion
- 30 Dec 2026 (estimated)
- First posted
- 13 Aug 2026 (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.
To determine the efficacy of citicoline in improving cerebral blood flow parameters and neurological status among neonates with hypoxic-ischemic encephalopathy using Doppler resistive index and Sarnat-Sarnat score after 72 hours of therapy.
Detailed description
Hypoxic-ischemic encephalopathy (HIE) is a leading cause of neonatal brain injury worldwide. In the developed world, the incidence is estimated at up to 8 per 1,000 live births, while in developing countries, estimates are as high as 26 per 1,000 live births. Approximately 20-30% of infants with HIE die in the neonatal period, and 33-50% of survivors are left with permanent neurodevelopmental abnormalities.1 HIE can be classified into mild (Stage I), moderate (Stage II), and severe (Stage III) based on the Sarnat and Sarnat staging system(Table 1), with stage II and III being associated with the highest morbidity and mortality.
Therapeutic hypothermia remains the standard therapy for HIE. However, its availability, high costs, need for specialized equipment and monitoring limit its use in developing countries like Pakistan, therefore alternative neuroprotective agents are used however there is still no consensus regarding which agent is the most effective. Citicoline (cytidine diphosphate choline) has demonstrated several neuroprotective mechanisms. It helps preserve neuronal membrane integrity by maintaining phospholipids while decreasing phospholipase A2 activity and oxidative damage.2 It also enhances phosphatidylcholine synthesis and promotes glutathione production, thereby decreasing free-radical-mediated neuronal injury. Experimental studies further suggest neuroprotective roles of citicoline as it modulates excitotoxicity by decreasing glutamate levels.3,4 These combined effects may contribute to improved neuronal survival and recovery after hypoxic-ischemic insults. Long term effects have been studied however no study evaluates short term improvement from therapy.
Resistive Index is a parameter assessed on cranial doppler ultrasonography, it is difference between peak systolic and end diastolic pressures in the anterior cerebral arteries, normal value is 0.68-0.72 5it demonstrates cerebral blood flow changes due to hypoxia, lower values have been associated with worse neurological outcome.5 RI has been studied in comparison to MRI and also its changes pre and post therapeutic hypothermia, and has been found to be useful tool6,7. American Academy of Neurology and Practice Committee of the Child Neurology Society recommends RI and end diastolic flow velocity (EDFV) in the anterior cerebral artery to assess cerebral perfusion and early prediction of outcome.8 This study is therefore designed to assess the effect of citicoline on cerebral resistive index and neurological improvement using Sarnat-Sarnat scoring after 3 days of treatment in neonates with hypoxic-ischemic encephalopathy. The findings may contribute to establishing evidence for adjunctive therapeutic strategies aimed at reducing neurological morbidity in affected neonates. Despite its clinical use in some centers, there is limited published evidence regarding the efficacy of citicoline in neonates with HIE.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention Group | Experimental | Drug: CiticolineThis will receive medicine citicoline with standard care |
| Control group | Placebo comparator | Other: Standard medical treatmentOnly receive standard care |
Who may qualify
- Ages
- 0 to 24 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- All inborn neonates diagnosed with APGAR score (Table 2) less then 8/10 at 5 min of life presenting to the emergency room within the first day of life.
- Outborn babies admitted in the last 24 hours with history or clinical features of perinatal asphyxia.
Key exclusion criteria (5 listed)
- Neonates who have received therapeutic hypothermia
- Neonates with congenital, developmental or chromosomal malformations
- Significant antenatal risk factors leading to early-onset sepsis\DIC or CNS depression unrelated to asphyxia
- Preterm neonates <35 weeks
- No consent could be obtained
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 |
|---|---|---|
| CiticolineThis group will receive drug and standard care | Drug | Intervention Group |
| Standard medical treatmentThis group will receive only standard care | Other | Control group |
Primary outcome
Sarnat and Sarnat scoring
Time frame: enrollment to 72 hours
Cerebral Resistive Index
Time frame: Enrollment to 72 hours
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2026.
- Background: PubMed 37173784Salamah A, El Amrousy D, Elsheikh M, Mehrez M. Citicoline in hypoxic ischemic encephalopathy in neonates: a randomized controlled trial. Ital J Pediatr. 2023 May 12;49(1):55. doi: 10.1186/s13052-023-01452-5.
- Background: PubMed 20144981Edwards AD, Brocklehurst P, Gunn AJ, Halliday H, Juszczak E, Levene M, Strohm B, Thoresen M, Whitelaw A, Azzopardi D. Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: synthesis and meta-analysis of trial data. BMJ. 2010 Feb 9;340:c363. doi: 10.1136/bmj.c363.
- Background: PubMed 26609871Gerner GJ, Burton VJ, Poretti A, Bosemani T, Cristofalo E, Tekes A, Seyfert D, Parkinson C, Leppert M, Allen M, Huisman TA, Northington FJ, Johnston MV. Transfontanellar duplex brain ultrasonography resistive indices as a prognostic tool in neonatal hypoxic-ischemic encephalopathy before and after treatment with therapeutic hypothermia. J Perinatol. 2016 Mar;36(3):202-6. doi: 10.1038/jp.2015.169. Epub 2015 Nov 26.
- Background: PubMed 32842070Snyder EJ, Perin J, Chavez-Valdez R, Northington FJ, Lee JK, Tekes A. Head Ultrasound Resistive Indices Are Associated With Brain Injury on Diffusion Tensor Imaging Magnetic Resonance Imaging in Neonates With Hypoxic-Ischemic Encephalopathy. J Comput Assist Tomogr. 2020 Sep/Oct;44(5):687-691. doi: 10.1097/RCT.0000000000001069.
- Background: PubMed 15686962Hurtado O, Moro MA, Cardenas A, Sanchez V, Fernandez-Tome P, Leza JC, Lorenzo P, Secades JJ, Lozano R, Davalos A, Castillo J, Lizasoain I. Neuroprotection afforded by prior citicoline administration in experimental brain ischemia: effects on glutamate transport. Neurobiol Dis. 2005 Mar;18(2):336-45. doi: 10.1016/j.nbd.2004.10.006.
- Background: PubMed 11796739Adibhatla RM, Hatcher JF, Dempsey RJ. Citicoline: neuroprotective mechanisms in cerebral ischemia. J Neurochem. 2002 Jan;80(1):12-23. doi: 10.1046/j.0022-3042.2001.00697.x.
- BackgroundCohen SS, Sprecher AJ, Acharya KK. Hypoxic-ischemic encephalopathy. In: Kliegman RM, St. Geme JW, Blum NJ, Tasker RC, Wilson KM, Schuh AM, Mack CL, editors. Nelson Textbook of Pediatrics. 22nd ed. Vol 1. Philadelphia: Elsevier; 2024. p. 1062.
- Individual participant dataSharing planned: Undecided
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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.
Romisa Rehman principal investigator
Hyatabad Medical Complex
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Citicoline and Standard medical treatment in people with Hypoxic Ischaemic Encephalopathy (HIE), run by Khyber Girls Medical College at 1 site in Pakistan.
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 5 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: opening soon, as of the sponsor's last update on 24 Aug 2026. 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 Pakistan. 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Romisa Rehman, FCPS, MRCPCH (00923219059305, measa_awan@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sarnat and Sarnat scoring (time frame: enrollment to 72 hours). The study lists 2 primary outcomes in all. 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 NCT07763145, which also lists 7 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 24 Aug 2026.