Neonatal EncephalopathyPhase 1SANE-01NCT02812433
Sildenafil Administration to Treat Neonatal Encephalopathy
A Phase 1 study testing Sildenafil and Ora-Blend in people with Neonatal Encephalopathy, run by McGill University Health Centre/Research Institute of the McGill University Health Centre at 1 site in Canada.
Trial summary
Despite improvements in neonatal care, birth asphyxia in term newborns remains a serious condition causing significant mortality and long-term morbidity, including cerebral palsy and mental retardation. Currently, no treatment exists to repair brain injuries secondary to neonatal asphyxia. Read more about this study
- Who is it for?
- Ages 0 minutes to 48 hours
- Conditions the study is for
- Neonatal Encephalopathy
- What is being tested?
- Sildenafil and Ora-Blend
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- 1 siteCanada
- Study dates
- Jul 2016to Jan 2022
- Phase
- Phase 1
- 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 0 minutes to 48 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Male and female asphyxiated newborns meeting the criteria for induced hypothermia:
- Gestational age ≥ 36 weeks and birth weight ≥ 1800 g
- Evidence of fetal distress, such as a history of an acute perinatal event, a cord pH ≤ 7.0 or base deficit ≤ - 16 mEq/L
- Evidence of neonatal distress, such as an Apgar score ≤ 5 at 10 minutes, a postnatal blood gas pH obtained within the first hour of life ≤ 7.0 or base deficit ≤ - 16 mEq/L, or a continued need for ventilation initiated at birth and continued for at least 10 minutes
- Evidence of moderate to severe neonatal encephalopathy by an abnormal neurological exam and/or an amplitude-integrated electroencephalogram (aEEG) These newborns will receive whole-body cooling to an esophageal temperature of 33.5°C, initiated within the first 6 hours of life, continued for 72 hours, and then they were slowly rewarmed using standard protocol .
- Evidence on a brain MRI performed on day 2 of life (while they are treated with hypothermia) of any type of brain parenchymal injury patterns typically encountered in asphyxiated newborns.
- If they meet the criteria for hypothermia treatment and demonstrate brain injury on day 2 of life, they will be randomized to sildenafil or placebo treatment.
Who cannot join
- Newborns with complex congenital heart disease
- Newborns with cerebral malformations
- Newborns with genetic syndrome
- Newborns with intraventricular and/or intraparenchymal hemorrhage on the MRI performed on day 2 of life
- Moribund infants not expected to survive
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Sildenafil Administration to Treat Neonatal Encephalopathy (SANE) and Repair Brain Injury Secondary to Birth Asphyxia: A Randomized, Double-blind, Placebo-controlled Pilot Phase Ib Study
Despite improvements in neonatal care, birth asphyxia in term newborns remains a serious condition causing significant mortality and long-term morbidity, including cerebral palsy and mental retardation. Currently, no treatment exists to repair brain injuries secondary to neonatal asphyxia. The only available treatment for this condition is hypothermia that may prevent but not repair the development of brain injury. The success of this therapy is limited.
Sildenafil already is used with some newborns for other purposes (i.e., persistent pulmonary hypertension), but, surprisingly, its effect on the newborn brain has never been studied systematically. The findings of the investigators in the rat model of term neonatal encephalopathy demonstrated that the administration of sildenafil following asphyxia promotes brain injury recovery. Thus, the investigators hypothesize that sildenafil may improve neurodevelopmental outcome in term asphyxiated newborns, in whom hypothermia treatment has failed to prevent the development of brain injury.
Read the detailed description
Before being able to run a large multicenter randomized trial to prove this hypothesis, the investigators need to run a phase Ib pilot trial to ensure the feasibility and safety of using sildenafil in this population of newborns. Thus, for this phase Ib study, the investigators hypothesize that sildenafil can be safely used with term asphyxiated newborns treated with hypothermia. The investigators will test this hypothesis with the following specific aims:
- Safety (primary): ensure that sildenafil can be safely used in asphyxiated newborns treated with hypothermia;
- Tolerability (secondary): study the pharmacokinetics and pharmacodynamics of sildenafil in these newborns;
- Efficacy (exploratory): determine whether sildenafil improves neurodevelopment at 2 years of age, decreases brain injury on day 30 of life and decreases neuroinflammation.
- Conditions
- Neonatal Encephalopathy
- Being tested
- Sildenafil, Ora-Blend
- Keywords
- birth asphyxia, brain, hypoxic-ischemic encephalopathy, neonate, neuroprotection, neurorestoration, newborn, sildenafil
- Medical subject headings
- Asphyxia Neonatorum, Hypoxia-Ischemia, Brain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SildenafilDrug
sildenafil 2 mg/kg/dose per os twice a day for seven consecutive days (from day 2 of life to day 9 of life) if brain injury on day 2 of life
Ora-BlendDrug
Ora-Blend, 2 mg/kg/dose per os twice a day for seven consecutive days (from day 2 of life to day 9 of life) if brain injury on day 2 of life
| Study group | Role | What they receive |
|---|---|---|
| Sildenafil | Active comparator | Sildenafil 2 mg/kg/dose per os twice a day for seven consecutive days (from day 2 of life to day 9 of life) if brain injury on day 2 of life Receives: Drug: Sildenafil |
| Ora-Blend | Placebo comparator | Ora-Blend 2 mg/kg/dose per os twice a day for seven consecutive days (from day 2 of life to day 9 of life) if brain injury on day 2 of life Receives: Drug: Ora-Blend |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serious adverse events
Close monitoring for adverse events such as death, hypotension, persistent pulmonary hypertension, altered renal or hepatic function, etc to assess the safety of sildenafil
Measured: Day 1 to 14 of life
Secondary outcomes (1)
Plasmatic concentrations of sildenafil and N-desmethyl sildenafil
To determine the tolerability of sildenafil (pharmacokinetics/pharmacodynamics)
Measured: Day 2 to 10 of life
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2016 (estimated)
- Study startJul 2016
- Primary completionJan 2019
- Study completionJan 2022
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 Neonatal EncephalopathyStudies of the same condition, open and under way.
- More trials run by McGill University Health Centre/Research Institute of the McGill University Health CentreThe 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- McGill University Health Centre/Research Institute of the McGill University Health Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Pia Wintermark, McGill University Health Centre/Research Institute of the McGill University Health Centre
- Investigators
- Pia Wintermark, Pia, Principal investigator, McGill University Health Centre/Research Institute of the McGill University Health Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02812433
- Sponsor's protocol ID
- SANE-01
- Acronym
- SANE-01
- Status last verified
- Feb 2022
- First submitted
- 19 Jun 2016
- Last updated
- 8 Feb 2022
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Wintermark P, Lapointe A, Steinhorn R, Rampakakis E, Burhenne J, Meid AD, Bajraktari-Sylejmani G, Khairy M, Altit G, Adamo MT, Poccia A, Gilbert G, Saint-Martin C, Toffoli D, Vachon J, Hailu E, Colin P, Haefeli WE. Feasibility and Safety of Sildenafil to Repair Brain Injury Secondary to Birth Asphyxia (SANE-01): A Randomized, Double-blind, Placebo-controlled Phase Ib Clinical Trial. J Pediatr. 2024 Mar;266:113879. doi: 10.1016/j.jpeds.2023.113879. Epub 2023 Dec 22.
PubMed 38142044Fei Q, Wang D, Yuan T. Comparison of Different Adjuvant Therapies for Hypothermia in Neonates with Hypoxic-Ischemic Encephalopathy: A Systematic Review and Network Meta-Analysis. Indian J Pediatr. 2024 Mar;91(3):235-241. doi: 10.1007/s12098-023-04563-3. Epub 2023 May 18.
PubMed 37199820
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sildenafil Administration to Treat Neonatal Encephalopathy (SANE) and Repair Brain Injury Secondary to Birth Asphyxia: A Randomized, Double-blind, Placebo-controlled Pilot Phase Ib Study
- ClinicalTrials.gov ID
- NCT02812433
- Acronym / sponsor ID
- SANE-01 / SANE-01
- Conditions
- Neonatal Encephalopathy
- Keywords
- birth asphyxia, brain, hypoxic-ischemic encephalopathy, neonate, neuroprotection, neurorestoration, newborn, sildenafil
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- McGill University Health Centre/Research Institute of the McGill University Health CentreUniversity, hospital or other
- Study start
- Jul 2016 (actual)
- Primary completion
- Jan 2019 (actual)
- Study completion
- Jan 2022 (actual)
- First posted
- 24 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.
Despite improvements in neonatal care, birth asphyxia in term newborns remains a serious condition causing significant mortality and long-term morbidity, including cerebral palsy and mental retardation. Currently, no treatment exists to repair brain injuries secondary to neonatal asphyxia. The only available treatment for this condition is hypothermia that may prevent but not repair the development of brain injury. The success of this therapy is limited.
Sildenafil already is used with some newborns for other purposes (i.e., persistent pulmonary hypertension), but, surprisingly, its effect on the newborn brain has never been studied systematically. The findings of the investigators in the rat model of term neonatal encephalopathy demonstrated that the administration of sildenafil following asphyxia promotes brain injury recovery. Thus, the investigators hypothesize that sildenafil may improve neurodevelopmental outcome in term asphyxiated newborns, in whom hypothermia treatment has failed to prevent the development of brain injury.
Detailed description
Before being able to run a large multicenter randomized trial to prove this hypothesis, the investigators need to run a phase Ib pilot trial to ensure the feasibility and safety of using sildenafil in this population of newborns. Thus, for this phase Ib study, the investigators hypothesize that sildenafil can be safely used with term asphyxiated newborns treated with hypothermia. The investigators will test this hypothesis with the following specific aims:
- Safety (primary): ensure that sildenafil can be safely used in asphyxiated newborns treated with hypothermia;
- Tolerability (secondary): study the pharmacokinetics and pharmacodynamics of sildenafil in these newborns;
- Efficacy (exploratory): determine whether sildenafil improves neurodevelopment at 2 years of age, decreases brain injury on day 30 of life and decreases neuroinflammation.
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 |
|---|---|---|
| Sildenafil | Active comparator | Drug: SildenafilSildenafil 2 mg/kg/dose per os twice a day for seven consecutive days (from day 2 of life to day 9 of life) if brain injury on day 2 of life |
| Ora-Blend | Placebo comparator | Drug: Ora-BlendOra-Blend 2 mg/kg/dose per os twice a day for seven consecutive days (from day 2 of life to day 9 of life) if brain injury on day 2 of life |
Who may qualify
- Ages
- 0 minutes to 48 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- Male and female asphyxiated newborns meeting the criteria for induced hypothermia:
- Evidence on a brain MRI performed on day 2 of life (while they are treated with hypothermia) of any type of brain parenchymal injury patterns typically encountered in asphyxiated newborns.
- If they meet the criteria for hypothermia treatment and demonstrate brain injury on day 2 of life, they will be randomized to sildenafil or placebo treatment.
Key exclusion criteria (5 listed)
- Newborns with complex congenital heart disease
- Newborns with cerebral malformations
- Newborns with genetic syndrome
- Newborns with intraventricular and/or intraparenchymal hemorrhage on the MRI performed on day 2 of life
- Moribund infants not expected to survive
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 |
|---|---|---|
| Sildenafilsildenafil 2 mg/kg/dose per os twice a day for seven consecutive days (from day 2 of life to day 9 of life) if brain injury on day 2 of life | Drug | Sildenafil |
| Ora-BlendOra-Blend, 2 mg/kg/dose per os twice a day for seven consecutive days (from day 2 of life to day 9 of life) if brain injury on day 2 of life | Drug | Ora-Blend |
Primary outcome
Serious adverse events
Time frame: Day 1 to 14 of life
Close monitoring for adverse events such as death, hypotension, persistent pulmonary hypertension, altered renal or hepatic function, etc to assess the safety of sildenafil
1 secondary outcome
Plasmatic concentrations of sildenafil and N-desmethyl sildenafil
Time frame: Day 2 to 10 of life
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 8 Feb 2022.
- Derived from this study: PubMed 38142044Wintermark P, Lapointe A, Steinhorn R, Rampakakis E, Burhenne J, Meid AD, Bajraktari-Sylejmani G, Khairy M, Altit G, Adamo MT, Poccia A, Gilbert G, Saint-Martin C, Toffoli D, Vachon J, Hailu E, Colin P, Haefeli WE. Feasibility and Safety of Sildenafil to Repair Brain Injury Secondary to Birth Asphyxia (SANE-01): A Randomized, Double-blind, Placebo-controlled Phase Ib Clinical Trial. J Pediatr. 2024 Mar;266:113879. doi: 10.1016/j.jpeds.2023.113879. Epub 2023 Dec 22.
- Derived from this study: PubMed 37199820Fei Q, Wang D, Yuan T. Comparison of Different Adjuvant Therapies for Hypothermia in Neonates with Hypoxic-Ischemic Encephalopathy: A Systematic Review and Network Meta-Analysis. Indian J Pediatr. 2024 Mar;91(3):235-241. doi: 10.1007/s12098-023-04563-3. Epub 2023 May 18.
- Related InfoLink provided by the sponsor.
- 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.
Pia Wintermark, Pia principal investigator
McGill University Health Centre/Research Institute of the McGill University Health Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Sildenafil and Ora-Blend in people with Neonatal Encephalopathy, run by McGill University Health Centre/Research Institute of the McGill University Health Centre at 1 site in Canada.
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 7 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: finished, as of the sponsor's last update on 8 Feb 2022. 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 Canada. 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 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.
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?
Serious adverse events (time frame: Day 1 to 14 of life). 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 NCT02812433, 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 8 Feb 2022.