Asphyxia NeonatorumSANNI 1NCT03177980
Fentanyl and Clonidine for Analgesia During Hypothermia in Term Asphyxiated Infants
An observational study of Asphyxia Neonatorum, run by Region Skane at 2 sites in Sweden.
Trial summary
A prospective pharmacokinetic (PK), pharmacodynamic (PD) and pharmacogenetic (PG) observation study, including the PK/PD/PG relationship, in fentanyl and clonidine administered for analgesia and sedation to term newborn asphyxiated infants receiving hypothermic treatment in the NICU. Read more about this study
- Who is it for?
- Ages 36 weeks and older
- Conditions the study is for
- Asphyxia Neonatorum
- What is being tested?
- Fentanyl and Fentanyl and clonidine
- How many people
- 49 participants
- Where
- 2 sitesSweden
- Study dates
- 24 Apr 2017to 1 Apr 2021
- Phase
- Observational
- 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 36 weeks and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Term asphyxiated infants admitted to the NICU for hypothermic treatment according to national and international guidelines and in need for analgesia according to pain assessment scales.
Who may be able to join
- Term infants (≥ gw 36+0) who, according to national guidelines (6), will receive hypothermic treatment following perinatal asphyxia, and are in need for analgesic or sedative medication according to clinical judgment based on Thomsons score and ALPS-Neo.
- Existing arterial or venous cannulas/catheters for repeated non-traumatic blood sampling
- Informed and written parental consent.
Who cannot join
- Atrioventricular (AV)- block I-III or heart rate < 70 .
- Serious coronary heart disease with need for postnatal surgery
- Mean arterial blood pressure <35 mmHg despite adequate treatment.
Trial locations and contacts
2 sites in 1 country.
Sweden2 sites
Skåne Uniersity Hospital
Lund, 221 85
Karolinska University Hospital
Stockholm, 171 76
About this study
Official title: Fentanyl and Clonidine for Analgesia During Hypothermia in Term Asphyxiated Infants - a Prospective Pharmacokinetic/Pharmacodynamic/Pharmacogenetic Observational Study. Cohort 1 in The SANNI Project.
A prospective pharmacokinetic (PK), pharmacodynamic (PD) and pharmacogenetic (PG) observation study, including the PK/PD/PG relationship, in fentanyl and clonidine administered for analgesia and sedation to term newborn asphyxiated infants receiving hypothermic treatment in the NICU.
Read the detailed description
All patients that are admitted to the study neonatal intensive care units (NICUs) for hypothermic treatment due to perinatal asphyxia are potential study patients, and their parents will be asked for consent.
The patient will be treated according to clinical guidelines and will be included in the study if in need for fentanyl and clonidine according to clinical judgment (HIE and pain scores) and as decided by the responsible clinical doctor. The dosing and administration of the drugs will be implemented according to an algorithm based on pain scoring results.
Apart from extra blood sampling, the bedside monitoring, investigations (electroencephalography (EEG), echocardiography (ECG), ultrasound of the brain and magnetic resonance imaging, (MRI)) and follow-up (neurologic examination) are the same as for all infants receiving hypothermia according to national and international guidelines. A brief standardised pain stimulation will be performed as part of the pain and stress assessment.
In total 50 infants will be included.
- Conditions
- Asphyxia Neonatorum
- Being tested
- Fentanyl, Fentanyl and clonidine
- Keywords
- Term infants, Analgesia, fentanyl, clonidine, pharmacokinetics, sedation, pharmacodynamics, neurophysiology, pharmacogenetics, asphyxia, hypothermia
- Medical subject headings
- Asphyxia Neonatorum, Agnosia, Asphyxia, Hypothermia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FentanylDrug
The dosing and administration of fentanyl will serve as the first drug intervention in infants in need of analgesia according to an algorithm based on pain scoring results.
Fentanyl and clonidineDrug
In infants in need of further analgesia clonidine will be administered as an add on drug according to an algorithm based on pain scoring results.
| Study group | Role | What they receive |
|---|---|---|
| Fentanyl | All infants in need of analgesia according to an algorithm based on pain assessment results will receive fentanyl as the first analgesic drug. Receives: Drug: Fentanyl | |
| Fentanyl and Clonidine | Infants in need of further analgesia according to an algorithm based on pain assessment results will receive fentanyl and clonidine as the analgesic drugs. Receives: Drug: Fentanyl and clonidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics (PK) of fentanyl and clonidine
Analysed with NONMEM (Non-linear Mixed Effect Modelling) populationbased PK statistics
Measured: Repeated blood samples over a total of 4 - 7 days]
Neurophysiologic response; by single cortical events and their dynamics in relation to PK
Analyse of single cortical events and their dynamics based on burst detection and measuring features of individual bursts as well as their mass statistical behaviour over time.
Measured: From admission to the department until 4- 72 h after reaching normothermia.]
Neurophysiologic response; longer term brain function in relation to PK
Assessment of longer term brain function using measures of long range correlation and brain activity cycling.
Measured: From admission to the department until 4- 72 h after reaching normothermia
Neurophysiologic response; global brain network function in relation to PK
Assessment of global brain network function will be based on Activation Synchrony Index.
Measured: From admission to the department until 4- 72 h after reaching normothermia
Secondary outcomes (4)
Change in/association between physiological parameters (heart rate, blood pressure, peripheral oxygen saturation and NIRS (near-infrared reflectance spectroscopy near-infrared spectroscopy) parameters) in relation to PK parameters
Measured: From admission to the department until 4- 72 h after reaching normothermia.
Change in pain responses as measured by pain assessment score for continuous pain/stress (ALPS-Neo and Comfort Neo) in relation to PK
Measured: From admission to the department until 4- 72 h after reaching normothermia.
Procedural pain response at a short standardized pain stimulation; as assessed with change in galvanic skin response, change in serum-cortisol and scored by a procedural pain assessment scale (PIPP-R) in relation to PK.
Measured: Once during stable treatment with hypothermia and 6 hours of unchanged medication
Pharmacogenetic profile in relation to PK and PD results; how PK/PD phenotypes depend on pharmacogenetic (PG) profiles.
Measured: One blood sample during study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2017
- Study start24 Apr 2017
- Primary completion1 Apr 2021
- Study completion1 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Asphyxia NeonatorumStudies of the same condition, open and under way.
- More trials run by Region SkaneThe 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
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Region Skane
- Sponsor type
- University, hospital or other
- Collaborators
- Lund University, Karolinska Institutet, Helsinki University Central Hospital, Great Ormond Street Hospital for Children NHS Foundation Trust, Örebro University, Sweden, The Swedish Research Council, University of Colorado, Denver, University of Tartu
- Responsible party
- Sponsor
- Investigators
- Elisabeth Norman, MD, Principal investigator, Region Skane and Lunds University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03177980
- Sponsor's protocol ID
- 2015-002470-20
- Other IDs
- 2015
- Acronym
- SANNI 1
- Status last verified
- Jun 2021
- First submitted
- 21 Apr 2017
- Last updated
- 9 Jun 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fentanyl and Clonidine for Analgesia During Hypothermia in Term Asphyxiated Infants - a Prospective Pharmacokinetic/Pharmacodynamic/Pharmacogenetic Observational Study. Cohort 1 in The SANNI Project.
- ClinicalTrials.gov ID
- NCT03177980
- Acronym / sponsor ID
- SANNI 1 / 2015-002470-20
- Conditions
- Asphyxia Neonatorum
- Keywords
- Term infants, Analgesia, fentanyl, clonidine, pharmacokinetics, sedation, pharmacodynamics, neurophysiology
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Region SkaneUniversity, hospital or other
- Collaborators
- Lund University, Karolinska Institutet, Helsinki University Central Hospital, Great Ormond Street Hospital for Children NHS Foundation Trust, Örebro University, Sweden, The Swedish Research Council, University of Colorado, Denver, University of Tartu
- Study start
- 24 Apr 2017 (actual)
- Primary completion
- 1 Apr 2021 (actual)
- Study completion
- 1 Apr 2021 (actual)
- First posted
- 6 Jun 2017 (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.
A prospective pharmacokinetic (PK), pharmacodynamic (PD) and pharmacogenetic (PG) observation study, including the PK/PD/PG relationship, in fentanyl and clonidine administered for analgesia and sedation to term newborn asphyxiated infants receiving hypothermic treatment in the NICU.
Detailed description
All patients that are admitted to the study neonatal intensive care units (NICUs) for hypothermic treatment due to perinatal asphyxia are potential study patients, and their parents will be asked for consent.
The patient will be treated according to clinical guidelines and will be included in the study if in need for fentanyl and clonidine according to clinical judgment (HIE and pain scores) and as decided by the responsible clinical doctor. The dosing and administration of the drugs will be implemented according to an algorithm based on pain scoring results.
Apart from extra blood sampling, the bedside monitoring, investigations (electroencephalography (EEG), echocardiography (ECG), ultrasound of the brain and magnetic resonance imaging, (MRI)) and follow-up (neurologic examination) are the same as for all infants receiving hypothermia according to national and international guidelines. A brief standardised pain stimulation will be performed as part of the pain and stress assessment.
In total 50 infants will be included.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fentanyl | – | Drug: FentanylAll infants in need of analgesia according to an algorithm based on pain assessment results will receive fentanyl as the first analgesic drug. |
| Fentanyl and Clonidine | – | Drug: Fentanyl and clonidineInfants in need of further analgesia according to an algorithm based on pain assessment results will receive fentanyl and clonidine as the analgesic drugs. |
Who may qualify
- Ages
- 36 weeks and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Term asphyxiated infants admitted to the NICU for hypothermic treatment according to national and international guidelines and in need for analgesia according to pain assessment scales.
Key inclusion criteria (3 listed)
- Term infants (≥ gw 36+0) who, according to national guidelines (6), will receive hypothermic treatment following perinatal asphyxia, and are in need for analgesic or sedative medication according to clinical judgment based on Thomsons score and ALPS-Neo.
- Existing arterial or venous cannulas/catheters for repeated non-traumatic blood sampling
- Informed and written parental consent.
Key exclusion criteria (3 listed)
- Atrioventricular (AV)- block I-III or heart rate < 70 .
- Serious coronary heart disease with need for postnatal surgery
- Mean arterial blood pressure <35 mmHg despite adequate treatment.
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 |
|---|---|---|
| FentanylThe dosing and administration of fentanyl will serve as the first drug intervention in infants in need of analgesia according to an algorithm based on pain scoring results. | Drug | Fentanyl |
| Fentanyl and clonidineIn infants in need of further analgesia clonidine will be administered as an add on drug according to an algorithm based on pain scoring results. | Drug | Fentanyl and Clonidine |
Primary outcome
Pharmacokinetics (PK) of fentanyl and clonidine
Time frame: Repeated blood samples over a total of 4 - 7 days]
Analysed with NONMEM (Non-linear Mixed Effect Modelling) populationbased PK statistics
Neurophysiologic response; by single cortical events and their dynamics in relation to PK
Time frame: From admission to the department until 4- 72 h after reaching normothermia.]
Analyse of single cortical events and their dynamics based on burst detection and measuring features of individual bursts as well as their mass statistical behaviour over time.
Neurophysiologic response; longer term brain function in relation to PK
Time frame: From admission to the department until 4- 72 h after reaching normothermia
Assessment of longer term brain function using measures of long range correlation and brain activity cycling.
Neurophysiologic response; global brain network function in relation to PK
Time frame: From admission to the department until 4- 72 h after reaching normothermia
Assessment of global brain network function will be based on Activation Synchrony Index.
4 secondary outcomes
Change in/association between physiological parameters (heart rate, blood pressure, peripheral oxygen saturation and NIRS (near-infrared reflectance spectroscopy near-infrared spectroscopy) parameters) in relation to PK parameters
Time frame: From admission to the department until 4- 72 h after reaching normothermia.
Change in pain responses as measured by pain assessment score for continuous pain/stress (ALPS-Neo and Comfort Neo) in relation to PK
Time frame: From admission to the department until 4- 72 h after reaching normothermia.
Procedural pain response at a short standardized pain stimulation; as assessed with change in galvanic skin response, change in serum-cortisol and scored by a procedural pain assessment scale (PIPP-R) in relation to PK.
Time frame: Once during stable treatment with hypothermia and 6 hours of unchanged medication
Pharmacogenetic profile in relation to PK and PD results; how PK/PD phenotypes depend on pharmacogenetic (PG) profiles.
Time frame: One blood sample during study
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 9 Jun 2021.
- 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.
Elisabeth Norman, MD principal investigator
Region Skane and Lunds University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Asphyxia Neonatorum, run by Region Skane at 2 sites in Sweden.
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 3 inclusion and 3 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 9 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Sweden. 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.
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?
Pharmacokinetics (PK) of fentanyl and clonidine (time frame: Repeated blood samples over a total of 4 - 7 days]). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Jun 2021.