Intensive Care, NeonatalNCT04928651

Clonidine for Analgesia to Preterm Infants During Neonatal Intensive Care

An observational study of Intensive Care, Neonatal and Analgesia, run by Region Skane at 2 sites in Sweden.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

A prospective pharmacokinetic (PK), pharmacodynamic (PD) and pharmacogenetic (PG) observation study, including the PK/PD/PG relationship, in clonidine administered for analgesia and sedation to preterm newborn infants receiving neonatal intensive care. Phase 3 - therapeutic confirmatory study Read more about this study

Who is it for?: Ages Up to 37 weeks
Conditions the study is for: Intensive Care, Neonatal, Analgesia, Hypnotics and Sedatives
What is being tested?: Clonidine
How many people: 40 participants
Where: 2 sitesSweden
Study dates: 6 Apr 2018to 13 May 2022
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 Up to 37 weeks
All sexes
No healthy volunteers
Child

Study population: Sick preterm infants admitted to the NICU in need for analgesic or sedative medication according to clinical judgment.

Who may be able to join

Preterm infants (< gw 37+0) who are in need for analgesic or sedative medication according to clinical judgment (scoring with pain assessment scales; ALPS-Neo and Comfort-Neo)
Existing arterial or venous cannulas/catheters for repeated non-traumatic blood sampling
Informed and written parental consent

Who cannot join

Hemodynamic instability (same as in clinical routine).
Cardiac malformations in need for postnatal surgery.
Any serious medical condition or ethical issues that could, in the Investigators opinion, interfere with the study procedures.

Trial locations and contacts

2 sites in 1 country.

Sweden2 sites

Skane University Hospital
Lund, 221 85
Marco Bartocci
Stockholm, 171 76

Other trials in Sweden

About this study

Official title: Clonidine for Analgesia to Preterm Infants During Neonatal Intensive Care - a Prospective Pharmacokinetic/Pharmacodynamic/Pharmacogenetic Observational Study. Cohort 2 in The SANNI Project

Read the detailed description

All preterm infants that are admitted to the study neonatal intensive care units (NICUs) for neonatal intensive care 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 clonidine according to clinical judgment (pain scores) and as decided by the responsible clinical doctor. The dosing and administration of the drug 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 follow-up (neurologic examination and magnetic resonance imaging, MRI) are the same as for all preterm infants according to local and national guidelines.

In total 100 infants will be included.

Conditions: Intensive Care, Neonatal, Analgesia, Hypnotics and Sedatives
Being tested: Clonidine
Medical subject headings: Agnosia

What participants receive

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

ClonidineDrug
Clonidine will be administered to preterm infants in need of analgesia and sedation; either as the primary drug for comfort and light sedation or as an "add-on" drug to opioids according to an algorithm based on pain and sedative scoring results. Opioids are mostly given to postoperative patients. These drugs (morphine or fentanyl) will not be studied, but a baseline PK sample will be taken to correlate to the baseline aEEG.

Study groups in NCT04928651
Study group	Role	What they receive
Clonidine		Preterm infants (< gw 37+0) who are in need for analgesic or sedative medication will receive treatment with clonidine according to an algorithm based on pain and sedative scoring results Receives: Drug: Clonidine

What is being measured

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

Pharmacokinetics (PK) of clonidine; S-concentration
Clonidine analyses will be performed with LC-MS standard assay on a Waters ultra-pressure liquid chromatography (UPLC)-MS/MS system and then statistically analysed with NONMEM (Non-linear Mixed Effect Modelling) populationbased PK statistics
Measured: Repeated blood samples (5 minutes after the loading dose, just before start of the clonidine infusion and at 1 hour, 24 hours, 48 hours and 72 hours after start of the infusion
Pharmacokinetics (PK) of clonidine; elimination half-time
Statistical analyses will be performed with NONMEM (Non-linear Mixed Effect Modelling) populationbased PK statistics
Measured: Data from repeated blood samples (5 minutes after the loading dose, just before start of the clonidine infusion and at 1 hour, 24 hours, 48 hours and 72 hours after start of the infusion
Pharmacokinetics (PK) of clonidine; clearance
Statistical analyses will be performed with NONMEM (Non-linear Mixed Effect Modelling) populationbased PK statistics
Measured: Data from repeated blood samples (5 minutes after the loading dose, just before start of the clonidine infusion and at 1 hour, 24 hours, 48 hours and 72 hours after start of the infusion
Pharmacokinetics (PK) of clonidine; volume of distribution
Statistical analyses will be performed with NONMEM (Non-linear Mixed Effect Modelling) populationbased PK statistics
Measured: Data from repeated blood samples (5 minutes after the loading dose, just before start of the clonidine infusion and at 1 hour, 24 hours, 48 hours and 72 hours after start of the infusion
Neurophysiologic amplitude-integrated EEG response 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 30 minutes before start of treatment until 72 hours after start of treatment.
Neurophysiologic amplitude-integrated EEG 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 30 minutes before start of treatment until 72 hours after start of treatment.
Neurophysiologic amplitude-integrated EEG response; assessment of global brain network function in relation to PK
Assessment of global brain network function will be based on Activation Synchrony Index.
Measured: From 30 minutes before start of treatment until 72 hours after start of treatment.

Secondary outcomes (11)

Change in/association between heart rate in relation to PK .
The heart rate will be monitored 1/second according to clinical routine in the neonatal intensive care, and concomitantly downloaded into the aEEG (amplitude integrated electroencephalography) monitor. The change will be described as percentage increase/decrease
Measured: From 30 minutes before start of treatment until 72 hours.
Change in/association between blood pressure (systolic, diastolic and mean arterial blood pressure) in relation to PK .
The blood pressure will be monitored 1/second according to clinical routine in the neonatal intensive care, and concomitantly downloaded into the aEEG (amplitude integrated electroencephalography) monitor. The change will be described as percentage increase/decrease
Measured: From 30 minutes before start of treatment until 72 hours.
Change in/association between peripheral oxygen saturation in relation to PK .
The peripheral oxygenation will be monitored 1/second according to clinical routine in the neonatal intensive care, and concomitantly downloaded into the aEEG (amplitude integrated electroencephalography) monitor. The change will be described as percentage increase/decrease
Measured: From 30 minutes before start of treatment until 72 hours.
Change in NIRS (near-infrared spectroscopy) response in relation to PK .
The NIRS registration will be sampled into a USB and downloaded and analysed. The change will be described as percentage increase/decrease
Measured: From 30 minutes before start of treatment until 72 hours.
Change in pain, stress and behavioral state as assessed with a pain scale for continuous pain/stress (Astrid Lindgrens and Lund childrens hospitals Pain and stress assessment scale for Preterm and Sick newborn infants, ALPS-Neo) in relation to PK.
Change in pain responses as measured by pain assessment scores for continuous pain/stress, The Astrid Lindgren and Lund Children's Hospitals Pain and Stress Assessment Scale for Preterm and sick Newborn Infants (ALPS-Neo) in relation to PK. This scale evaluates facial expression, breathing pattern, tone of extremities, hand/foot activity and level of activity, rated 0-2. Will be assessed hourly according to clinical routine. The relation to PK will be analysed with the help of NONMEM statistics
Measured: From 30 minutes before start of treatment until 72 hours.
Change in pain, stress and behavioral state as assessed with a pain scale for continuous pain/stress (The COMFORT-Neo scale) in relation to PK
Change in pain responses as measured by pain assessment scores for continuous pain/stress, the Comfort Neo, in relation to PK. This scale evaluates alertness, calmness/agitation, respiratory response, crying, body movement, facial tension and muscle tone, rated 0-5. Will be assessed hourly according to clinical routine. The relation to PK will be analysed with the help of NONMEM statistics
Measured: From 30 minutes before start of treatment until 72 hours.
Procedural pain response in relation to PK: assessed with change in galvanic skin response
Procedural pain response at a short standardized pain stimulation; as assessed with change in galvanic skin response in relation to PK. The change will be described as percentage increase/decrease
Measured: At one occasion during the study period (72 hours) when the analgesic treatment has not been changed the last six hours.
Procedural pain response in relation to PK: change in serum-cortisol
Procedural pain response at a short standardized pain stimulation; change in serum-cortisol in relation to PK. The relation to PK will be analysed with NONMEM statistics.
Measured: At one occasion during the study period (72 hours) when the analgesic treatment has not been changed the last six hours.
Procedural pain response in relation to PK as assessed with the Premature Infant Pain Profile - revised, PIPP-R, a scale for assessment of procedural pain.
Procedural pain response at a short standardized pain stimulation; as scored by a procedural pain assessment scale (Premature Infant Pain Profile - revised, PIPP-R) in relation to PK. The relation to PK will be analysed with NONMEM statistics.
Measured: At one occasion during the study period (72 hours) when the analgesic treatment has not been changed the last six hours.
Pharmacogenetic profile in relation to PK results how PK phenotypes depend on pharmacogenetic (PG) profiles.
Whole exome sequencing will be conducted, specific pain related genes investigated and related to PK
Measured: One blood sample during the study period of 72 hours
Pharmacogenetic profile in relation to PD results
Whole exome sequencing will be conducted, specific pain related genes investigated and related to pain response as assessed with scores, serum cortisol and skin conductance.
Measured: One blood sample during the study period of 72 hours

Timeline

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

6 Apr 201813 May 2022

First posted16 Jun 2021
Study start6 Apr 2018
Primary completion13 May 2022
Study completion13 May 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Intensive Care, NeonatalStudies 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: 40 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04928651
Sponsor's protocol ID: 2017-005091-26
Other IDs: 2017
Status last verified: Feb 2023
First submitted: 23 Mar 2018
Last updated: 4 Aug 2023
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

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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Study at a glance

From the registry record, last updated by the sponsor on 4 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Clonidine for Analgesia to Preterm Infants During Neonatal Intensive Care - a Prospective Pharmacokinetic/Pharmacodynamic/Pharmacogenetic Observational Study. Cohort 2 in The SANNI Project
ClinicalTrials.gov ID: NCT04928651
Acronym / sponsor ID: 2017-005091-26
Conditions: Intensive Care, Neonatal, Analgesia, Hypnotics and Sedatives
Study type: Observational
Recruitment status: Completed
Enrolment: 40 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 Tartu, University of Colorado, Denver
Study start: 6 Apr 2018 (actual)
Primary completion: 13 May 2022 (actual)
Study completion: 13 May 2022 (actual)
First posted: 16 Jun 2021 (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.

Detailed description

All preterm infants that are admitted to the study neonatal intensive care units (NICUs) for neonatal intensive care are potential study patients, and their parents will be asked for consent.

In total 100 infants will be included.

Study design

Observational model: Case only
Time perspective: Prospective
Number of arms: 1

Arm	Type	Receives
Clonidine	–	Drug: ClonidinePreterm infants (< gw 37+0) who are in need for analgesic or sedative medication will receive treatment with clonidine according to an algorithm based on pain and sedative scoring results

Who may qualify

Ages: Up to 37 weeks
Sex: All
Healthy volunteers: Not accepted
Age groups: Child
Study population: Sick preterm infants admitted to the NICU in need for analgesic or sedative medication according to clinical judgment.

Key inclusion criteria (3 listed)

Preterm infants (< gw 37+0) who are in need for analgesic or sedative medication according to clinical judgment (scoring with pain assessment scales; ALPS-Neo and Comfort-Neo)
Existing arterial or venous cannulas/catheters for repeated non-traumatic blood sampling
Informed and written parental consent

Key exclusion criteria (3 listed)

Hemodynamic instability (same as in clinical routine).
Cardiac malformations in need for postnatal surgery.
Any serious medical condition or ethical issues that could, in the Investigators opinion, interfere with the study procedures.

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
ClonidineClonidine will be administered to preterm infants in need of analgesia and sedation; either as the primary drug for comfort and light sedation or as an "add-on" drug to opioids according to an algorithm based on pain and sedative scoring results. Opioids are mostly given to postoperative patients. These drugs (morphine or fentanyl) will not be studied, but a baseline PK sample will be taken to correlate to the baseline aEEG.	Drug	Clonidine

Primary outcome

Pharmacokinetics (PK) of clonidine; S-concentration
Time frame: Repeated blood samples (5 minutes after the loading dose, just before start of the clonidine infusion and at 1 hour, 24 hours, 48 hours and 72 hours after start of the infusion
Clonidine analyses will be performed with LC-MS standard assay on a Waters ultra-pressure liquid chromatography (UPLC)-MS/MS system and then statistically analysed with NONMEM (Non-linear Mixed Effect Modelling) populationbased PK statistics
Pharmacokinetics (PK) of clonidine; elimination half-time
Time frame: Data from repeated blood samples (5 minutes after the loading dose, just before start of the clonidine infusion and at 1 hour, 24 hours, 48 hours and 72 hours after start of the infusion
Statistical analyses will be performed with NONMEM (Non-linear Mixed Effect Modelling) populationbased PK statistics
Pharmacokinetics (PK) of clonidine; clearance
Time frame: Data from repeated blood samples (5 minutes after the loading dose, just before start of the clonidine infusion and at 1 hour, 24 hours, 48 hours and 72 hours after start of the infusion
Statistical analyses will be performed with NONMEM (Non-linear Mixed Effect Modelling) populationbased PK statistics
Pharmacokinetics (PK) of clonidine; volume of distribution
Time frame: Data from repeated blood samples (5 minutes after the loading dose, just before start of the clonidine infusion and at 1 hour, 24 hours, 48 hours and 72 hours after start of the infusion
Statistical analyses will be performed with NONMEM (Non-linear Mixed Effect Modelling) populationbased PK statistics
Neurophysiologic amplitude-integrated EEG response in relation to PK
Time frame: From 30 minutes before start of treatment until 72 hours after start of treatment.
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 amplitude-integrated EEG response; longer term brain function in relation to PK
Time frame: From 30 minutes before start of treatment until 72 hours after start of treatment.
Assessment of longer term brain function using measures of long range correlation and brain activity cycling.
Neurophysiologic amplitude-integrated EEG response; assessment of global brain network function in relation to PK
Time frame: From 30 minutes before start of treatment until 72 hours after start of treatment.
Assessment of global brain network function will be based on Activation Synchrony Index.

11 secondary outcomes

Change in/association between heart rate in relation to PK .
Time frame: From 30 minutes before start of treatment until 72 hours.
Change in/association between blood pressure (systolic, diastolic and mean arterial blood pressure) in relation to PK .
Time frame: From 30 minutes before start of treatment until 72 hours.
Change in/association between peripheral oxygen saturation in relation to PK .
Time frame: From 30 minutes before start of treatment until 72 hours.
Change in NIRS (near-infrared spectroscopy) response in relation to PK .
Time frame: From 30 minutes before start of treatment until 72 hours.
Change in pain, stress and behavioral state as assessed with a pain scale for continuous pain/stress (Astrid Lindgrens and Lund childrens hospitals Pain and stress assessment scale for Preterm and Sick newborn infants, ALPS-Neo) in relation to PK.
Time frame: From 30 minutes before start of treatment until 72 hours.
Change in pain, stress and behavioral state as assessed with a pain scale for continuous pain/stress (The COMFORT-Neo scale) in relation to PK
Time frame: From 30 minutes before start of treatment until 72 hours.
Procedural pain response in relation to PK: assessed with change in galvanic skin response
Time frame: At one occasion during the study period (72 hours) when the analgesic treatment has not been changed the last six hours.
Procedural pain response in relation to PK: change in serum-cortisol
Time frame: At one occasion during the study period (72 hours) when the analgesic treatment has not been changed the last six hours.
Procedural pain response in relation to PK as assessed with the Premature Infant Pain Profile - revised, PIPP-R, a scale for assessment of procedural pain.
Time frame: At one occasion during the study period (72 hours) when the analgesic treatment has not been changed the last six hours.
Pharmacogenetic profile in relation to PK results how PK phenotypes depend on pharmacogenetic (PG) profiles.
Time frame: One blood sample during the study period of 72 hours
Pharmacogenetic profile in relation to PD results
Time frame: One blood sample during the study period of 72 hours

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 4 Aug 2023.
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

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 Intensive Care, Neonatal and Analgesia, 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 4 Aug 2023. 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 clonidine; S-concentration (time frame: Repeated blood samples (5 minutes after the loading dose, just before start of the clonidine infusion and at 1 hour, 24 hours, 48 hours and 72 hours after start of the infusion). The study lists 7 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 NCT04928651.

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 4 Aug 2023.