Qt Interval, Variation inSSRIsNCT02492347
Effect of Antenatal SSRI Exposure on the QT Interval of Neonates
A study testing Electrocardiogram in people with Qt Interval, Variation in and Adverse Effect of Selective Serotonin Reuptake Inhibitors, run by University of Southampton at 1 site in United Kingdom.
Trial summary
Selective Serotonin Reuptake Inhibitors (SSRIs) are a group of antidepressants that suppress the re-absorption of a chemical called Serotonin in the brain, and improve mood. SSRI use in the treatment of mental health problems has increased greatly since their introduction in the 1980's. Read more about this study
- Who is it for?
- Ages 2 to 3 days
- Conditions the study is for
- Qt Interval, Variation in, Adverse Effect of Selective Serotonin Reuptake Inhibitors
- What is being tested?
- Electrocardiogram
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 88 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 18 Feb 2016to 18 Aug 2017
- Phase
- Interventional
- 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 2 to 3 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Neonates 37 weeks or more gestation at birth
- Age of parent/ person with parental responsibility being at least 16 years old
- Clinically well parent/ person with parental responsibility
- English Speaking parent/ person with parental responsibility
- Neonate at least 48 hours old
- Maternal SSRI use at any point in pregnancy
Show all 11Show fewer
- Neonate highlighted as at risk of infection and:-
- antibiotic therapy at less than 12 hours old;
- CRP x 2 <10mg/l;
- negative blood culture at 36-47 hours of age (depending on when antibiotic therapy was . commenced)
- clinically well on examination by ANNP/ Medical team.
Who cannot join
- Neonates less than 37 weeks gestation at birth
- Age of parent/ person with parental responsibility under 16 years old
- Neonate who is clinically unwell with risk of infection on examination
- Neonate with CRP greater than 10 mg/l
- Neonate with positive blood culture
- Neonate less than 48 hours old
Show all 14Show fewer
- Maternal cocaine misuse
- Maternal methadone use
- Maternal use of other antidepressants
- Known maternal or fetal structural cardiac abnormality
- Neonate with heart murmur at the time of the planned ECG
- Neonate presenting with congenital abnormality with a high incidence of associated cardiac malformations . . in current pregnancy (e.g., Trisomy 21)
- Neonate highlighted as at risk of infection and requiring antibiotic therapy.
- Maternal use of SSRIs in pregnancy
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University of Southampton
Southampton, Hampshire, SO17 1BJ
About this study
Official title: Is Antenatal Exposure to Selective Serotonin Reuptake Inhibitors (SSRIs) Associated With Prolongation of the QT Interval in Term Neonates (Greater Than 37 Complete Weeks Gestation)?
Selective Serotonin Reuptake Inhibitors (SSRIs) are a group of antidepressants that suppress the re-absorption of a chemical called Serotonin in the brain, and improve mood. SSRI use in the treatment of mental health problems has increased greatly since their introduction in the 1980's. When given in pregnancy they cause less fetal effects than other antidepressants. However they are still known to cause premature birth, heart defects and withdrawal symptoms in the baby. Withdrawal symptoms can occur in up to 30% of exposed babies, where as heart defects have been found to increase by 2-3 times against the normal rate of 1%. There is very limited information available, but it is also thought it may cause lengthening of a certain portion of the heart beat, the QT interval, which has been shown to lead to sudden death in adults. The QT interval will be looked at in this study, comparing babies exposed to SSRIs in pregnancy with unexposed babies.
The study will be based in the United Kingdom (UK), at the Maternity Unit of a District General Hospital, and will be carried out over 12-18 months.
Read more
A group of babies whose mothers took SSRIs whilst pregnant will have an Electrocardiogram (ECG) done when they are 2-3 days old. These will be compared with babies whose mothers did not, but whose babies were still in hospital because they were at risk of having an infection, but were found to be healthy.
The study hopes to see whether there is a link between SSRI use in pregnancy and lengthening of the QT interval and if so, extra surveillance may be considered for this group of babies.
Read the detailed description
The study will be carried out at the maternity unit of the local district general hospital. It is normal practice for women who have taken SSRIs in pregnancy to deliver at the local district general hospital, rather than at home or in the community, due to the possible problems with their babies.
Currently it is standard practice for a plan of care for after the baby is born (an ALERT) to be generated whilst the woman is pregnant. The ALERT form is developed by specialist nurses, Advanced Neonatal Nurse Practitioners (ANNPs) and Doctors specialising in newborn babies. The ALERT form details the recommended place of birth; length of expected hospital stay; known side effects of SSRIs; the monitoring that is done after birth and why; and whether breastfeeding is advised. This is returned to community midwifery staff to discuss with the woman ahead of delivery. When the woman who has taken SSRIs in her pregnancy comes to the maternity unit to deliver the ALERT form is activated. After birth she will be assessed by maternity staff and ANNPs to see if her baby is suitable for the study, and if so, she will be given an information leaflet and invitation letter when her baby is 12 hours old by these staff.
The other group of mothers that will be asked for the participation of their babies, will be those who require treatment with intravenous antibiotics for at least 36 hours, having been identified as being at risk of having an infection within 12 hours of being born. An infection marker, C-Reactive Protein (CRP) in their blood is measured, and if this remains normal after 18 hours and the baby is suitable for the study, the mother will be given an information leaflet and invitation letter by maternity staff/ ANNPs. Antibiotics will continue to be given to the baby for at least 36- 47 hours until a blood test shows whether they have an infection or not. If they don't have an infection and are healthy, they will be considered for this study.
Both groups of babies are regularly monitored by the staff in the maternity unit to make sure that any problems they have are acted on quickly. Both groups of babies would normally be in hospital for 36- 48 hours for this monitoring.
When the babies in both groups are 48-72 hours old, the ANNPs will ask the mother if she is happy for her baby to have an electrocardiogram (ECG) to look at their heart beat pattern. After consideration time, a consent form is signed, a data collection sheet completed, and the ECG is carried out on the baby. This will happen on the ward so there is minimal disruption to the mother and baby.
The ECG machine used is very accurate so if it shows the heart beat pattern is normal, the parents are told the result and can go home. The ANNPs and Doctors specialising in the care of newborn babies will check the result within 24 hours.
If the ECG machine says the heart beat pattern is not normal, then the baby remains in hospital, whilst the result is checked by the ANNPs and the Doctors specialising in the care of newborn babies, as soon as possible after it is taken. If the heart beat reading is abnormal, the ANNPs and Doctors specialising in the care of newborn babies will talk to the parents about further tests and other monitoring.
If the confirmed ECG result is known before discharge home, the General Practitioner (GP) / Community staff will be told of the study and the result, on the hospital discharge letter the mother takes home for them. If the family have gone home before this happens they will receive a confirmed normal result in the post. The confirmed result will also be added to the electronic hospital records.
In order to give statistically significant results, the study will be carried out over 12 -18 months, and involve 121 babies in each group. After 50 babies have had an ECG, the results will be reviewed to see what results are being seen and to see if the study is following the original plan/ time frame.
A statistician helped to determine how many babies would be needed for the study to show a difference between the two groups. However even if the difference is less than expected, the study may still point to the possibility of an association and provide useful data for future studies.
- Being tested
- Electrocardiogram
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ElectrocardiogramProcedure or surgery
The ECG is a non-invasive screening tool. It will be performed when the neonate is settled and comfortable. The electrodes used are made with soft jelly adhesive which is stored at room temperature. The procedure will be conducted in a timely manner, taking no longer than 15 minutes. The electrodes are easily removed, and the neonate redressed.
| Study group | Role | What they receive |
|---|---|---|
| Neonates exposed to AN SSRI use | Active comparator | A group of newborn babies who have been exposed to SSRIs in pregnancy will receive an Electrocardiogram at 48-72 hours of age. Receives: Procedure: Electrocardiogram |
| Neonates not exposed to AN SSRI use | Other | A group of newborn babies, who require treatment with intravenous antibiotics for at least 36 hours, having been identified as being at risk of having an infection within 12 hours of being born. They are subsequently confirmed as clinically well and will receive an Electrocardiogram at 48-72 hours of age. Receives: Procedure: Electrocardiogram |
What is being measured
The primary outcome is the main question the study is designed to answer.
QT interval on ECG of 48-72 hours old neonates
The range of QT intervals for this age group of neonates will be ascertained on ECG. Those outside the accepted norm of 2 deviations from the mean (>440msecs) will be highlighted as prolonged.
Measured: 48-72 hours old
Secondary outcomes (3)
SSRIs taken antenatally as stated on the data collection sheet.
The range of SSRIs taken in pregnancy locally will be extracted from the data collection sheet.
Measured: 48 -72 hours postpartum
Gestation at which SSRIs were taken as stated on the data collection sheet.
The timeline for SSRI use in pregnancy locally will be extracted from the data collection.
Measured: 48 -72 hours postpartum
Wellbeing as stated in hospital record at 6 months of age if prolonged QT interval on ECG at 48- 72 hours of age.
Mortality and morbidity assessment by reviewing the electronic patient record at 6 months of age of only those neonates who presented with early prolongation of the QT interval.
Measured: 6 months old
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2015 (estimated)
- Study start18 Feb 2016
- Primary completion18 Aug 2017
- Study completion18 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Qt Interval, Variation inStudies 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
- Screening
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Southampton
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02492347
- Sponsor's protocol ID
- 8442
- Acronym
- SSRIs
- Status last verified
- Nov 2017
- First submitted
- 17 Jun 2015
- Last updated
- 6 Nov 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided: Not personal details but details in questionnaire will be included in articles as a group. Undecided whether it will draw on individual aspects
Publications
Dubnov-Raz G, Juurlink DN, Fogelman R, Merlob P, Ito S, Koren G, Finkelstein Y. Antenatal use of selective serotonin-reuptake inhibitors and QT interval prolongation in newborns. Pediatrics. 2008 Sep;122(3):e710-5. doi: 10.1542/peds.2008-0658.
PubMed 18762507Lattimore KA, Donn SM, Kaciroti N, Kemper AR, Neal CR Jr, Vazquez DM. Selective serotonin reuptake inhibitor (SSRI) use during pregnancy and effects on the fetus and newborn: a meta-analysis. J Perinatol. 2005 Sep;25(9):595-604. doi: 10.1038/sj.jp.7211352.
PubMed 16015372Tuccori M, Testi A, Antonioli L, Fornai M, Montagnani S, Ghisu N, Colucci R, Corona T, Blandizzi C, Del Tacca M. Safety concerns associated with the use of serotonin reuptake inhibitors and other serotonergic/noradrenergic antidepressants during pregnancy: a review. Clin Ther. 2009 Jun;31 Pt 1:1426-53. doi: 10.1016/j.clinthera.2009.07.009.
PubMed 19698902Udechuku A, Nguyen T, Hill R, Szego K. Antidepressants in pregnancy: a systematic review. Aust N Z J Psychiatry. 2010 Nov;44(11):978-96. doi: 10.3109/00048674.2010.507543.
PubMed 21034181
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Is Antenatal Exposure to Selective Serotonin Reuptake Inhibitors (SSRIs) Associated With Prolongation of the QT Interval in Term Neonates (Greater Than 37 Complete Weeks Gestation)?
- ClinicalTrials.gov ID
- NCT02492347
- Acronym / sponsor ID
- SSRIs / 8442
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 88 participants (actual)
- Lead sponsor
- University of SouthamptonUniversity, hospital or other
- Study start
- 18 Feb 2016 (actual)
- Primary completion
- 18 Aug 2017 (actual)
- Study completion
- 18 Aug 2017 (actual)
- First posted
- 8 Jul 2015 (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.
Selective Serotonin Reuptake Inhibitors (SSRIs) are a group of antidepressants that suppress the re-absorption of a chemical called Serotonin in the brain, and improve mood. SSRI use in the treatment of mental health problems has increased greatly since their introduction in the 1980's. When given in pregnancy they cause less fetal effects than other antidepressants. However they are still known to cause premature birth, heart defects and withdrawal symptoms in the baby. Withdrawal symptoms can occur in up to 30% of exposed babies, where as heart defects have been found to increase by 2-3 times against the normal rate of 1%. There is very limited information available, but it is also thought it may cause lengthening of a certain portion of the heart beat, the QT interval, which has been shown to lead to sudden death in adults. The QT interval will be looked at in this study, comparing babies exposed to SSRIs in pregnancy with unexposed babies.
The study will be based in the United Kingdom (UK), at the Maternity Unit of a District General Hospital, and will be carried out over 12-18 months.
A group of babies whose mothers took SSRIs whilst pregnant will have an Electrocardiogram (ECG) done when they are 2-3 days old. These will be compared with babies whose mothers did not, but whose babies were still in hospital because they were at risk of having an infection, but were found to be healthy.
The study hopes to see whether there is a link between SSRI use in pregnancy and lengthening of the QT interval and if so, extra surveillance may be considered for this group of babies.
Detailed description
The study will be carried out at the maternity unit of the local district general hospital. It is normal practice for women who have taken SSRIs in pregnancy to deliver at the local district general hospital, rather than at home or in the community, due to the possible problems with their babies.
Currently it is standard practice for a plan of care for after the baby is born (an ALERT) to be generated whilst the woman is pregnant. The ALERT form is developed by specialist nurses, Advanced Neonatal Nurse Practitioners (ANNPs) and Doctors specialising in newborn babies. The ALERT form details the recommended place of birth; length of expected hospital stay; known side effects of SSRIs; the monitoring that is done after birth and why; and whether breastfeeding is advised. This is returned to community midwifery staff to discuss with the woman ahead of delivery. When the woman who has taken SSRIs in her pregnancy comes to the maternity unit to deliver the ALERT form is activated. After birth she will be assessed by maternity staff and ANNPs to see if her baby is suitable for the study, and if so, she will be given an information leaflet and invitation letter when her baby is 12 hours old by these staff.
The other group of mothers that will be asked for the participation of their babies, will be those who require treatment with intravenous antibiotics for at least 36 hours, having been identified as being at risk of having an infection within 12 hours of being born. An infection marker, C-Reactive Protein (CRP) in their blood is measured, and if this remains normal after 18 hours and the baby is suitable for the study, the mother will be given an information leaflet and invitation letter by maternity staff/ ANNPs. Antibiotics will continue to be given to the baby for at least 36- 47 hours until a blood test shows whether they have an infection or not. If they don't have an infection and are healthy, they will be considered for this study.
Both groups of babies are regularly monitored by the staff in the maternity unit to make sure that any problems they have are acted on quickly. Both groups of babies would normally be in hospital for 36- 48 hours for this monitoring.
When the babies in both groups are 48-72 hours old, the ANNPs will ask the mother if she is happy for her baby to have an electrocardiogram (ECG) to look at their heart beat pattern. After consideration time, a consent form is signed, a data collection sheet completed, and the ECG is carried out on the baby. This will happen on the ward so there is minimal disruption to the mother and baby.
The ECG machine used is very accurate so if it shows the heart beat pattern is normal, the parents are told the result and can go home. The ANNPs and Doctors specialising in the care of newborn babies will check the result within 24 hours.
If the ECG machine says the heart beat pattern is not normal, then the baby remains in hospital, whilst the result is checked by the ANNPs and the Doctors specialising in the care of newborn babies, as soon as possible after it is taken. If the heart beat reading is abnormal, the ANNPs and Doctors specialising in the care of newborn babies will talk to the parents about further tests and other monitoring.
If the confirmed ECG result is known before discharge home, the General Practitioner (GP) / Community staff will be told of the study and the result, on the hospital discharge letter the mother takes home for them. If the family have gone home before this happens they will receive a confirmed normal result in the post. The confirmed result will also be added to the electronic hospital records.
In order to give statistically significant results, the study will be carried out over 12 -18 months, and involve 121 babies in each group. After 50 babies have had an ECG, the results will be reviewed to see what results are being seen and to see if the study is following the original plan/ time frame.
A statistician helped to determine how many babies would be needed for the study to show a difference between the two groups. However even if the difference is less than expected, the study may still point to the possibility of an association and provide useful data for future studies.
Study design
- Primary purpose
- Screening
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Neonates exposed to AN SSRI use | Active comparator | Procedure: ElectrocardiogramA group of newborn babies who have been exposed to SSRIs in pregnancy will receive an Electrocardiogram at 48-72 hours of age. |
| Neonates not exposed to AN SSRI use | Other | Procedure: ElectrocardiogramA group of newborn babies, who require treatment with intravenous antibiotics for at least 36 hours, having been identified as being at risk of having an infection within 12 hours of being born. They are subsequently confirmed as clinically well and will receive an Electrocardiogram at 48-72 hours of age. |
Who may qualify
- Ages
- 2 to 3 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (11 listed)
- Neonates 37 weeks or more gestation at birth
- Age of parent/ person with parental responsibility being at least 16 years old
- Clinically well parent/ person with parental responsibility
- English Speaking parent/ person with parental responsibility
- Neonate at least 48 hours old
Key exclusion criteria (14 listed)
- Neonates less than 37 weeks gestation at birth
- Age of parent/ person with parental responsibility under 16 years old
- Neonate who is clinically unwell with risk of infection on examination
- Neonate with CRP greater than 10 mg/l
- Neonate with positive blood culture
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 |
|---|---|---|
| ElectrocardiogramThe ECG is a non-invasive screening tool. It will be performed when the neonate is settled and comfortable. The electrodes used are made with soft jelly adhesive which is stored at room temperature. The procedure will be conducted in a timely manner, taking no longer than 15 minutes. The electrodes are easily removed, and the neonate redressed. | Procedure or surgery | Neonates exposed to AN SSRI use, Neonates not exposed to AN SSRI use |
Primary outcome
QT interval on ECG of 48-72 hours old neonates
Time frame: 48-72 hours old
The range of QT intervals for this age group of neonates will be ascertained on ECG. Those outside the accepted norm of 2 deviations from the mean (>440msecs) will be highlighted as prolonged.
3 secondary outcomes
SSRIs taken antenatally as stated on the data collection sheet.
Time frame: 48 -72 hours postpartum
Gestation at which SSRIs were taken as stated on the data collection sheet.
Time frame: 48 -72 hours postpartum
Wellbeing as stated in hospital record at 6 months of age if prolonged QT interval on ECG at 48- 72 hours of age.
Time frame: 6 months old
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 6 Nov 2017.
- Background: PubMed 18762507Dubnov-Raz G, Juurlink DN, Fogelman R, Merlob P, Ito S, Koren G, Finkelstein Y. Antenatal use of selective serotonin-reuptake inhibitors and QT interval prolongation in newborns. Pediatrics. 2008 Sep;122(3):e710-5. doi: 10.1542/peds.2008-0658.
- Background: PubMed 16015372Lattimore KA, Donn SM, Kaciroti N, Kemper AR, Neal CR Jr, Vazquez DM. Selective serotonin reuptake inhibitor (SSRI) use during pregnancy and effects on the fetus and newborn: a meta-analysis. J Perinatol. 2005 Sep;25(9):595-604. doi: 10.1038/sj.jp.7211352.
- Background: PubMed 19698902Tuccori M, Testi A, Antonioli L, Fornai M, Montagnani S, Ghisu N, Colucci R, Corona T, Blandizzi C, Del Tacca M. Safety concerns associated with the use of serotonin reuptake inhibitors and other serotonergic/noradrenergic antidepressants during pregnancy: a review. Clin Ther. 2009 Jun;31 Pt 1:1426-53. doi: 10.1016/j.clinthera.2009.07.009.
- Background: PubMed 21034181Udechuku A, Nguyen T, Hill R, Szego K. Antidepressants in pregnancy: a systematic review. Aust N Z J Psychiatry. 2010 Nov;44(11):978-96. doi: 10.3109/00048674.2010.507543.
- Individual participant dataSharing planned: Undecided. Not personal details but details in questionnaire will be included in articles as a group. Undecided whether it will draw on individual aspects
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Electrocardiogram in people with Qt Interval, Variation in and Adverse Effect of Selective Serotonin Reuptake Inhibitors, run by University of Southampton at 1 site in United Kingdom.
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 11 inclusion and 14 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 6 Nov 2017. 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 United Kingdom. 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?
QT interval on ECG of 48-72 hours old neonates (time frame: 48-72 hours old). 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 NCT02492347, which also lists 4 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 6 Nov 2017.