Withdrawal SyndromePhase 2TIP-15-01NCT03645603
Efficacy and Safety of Dexmedetomidine During Weaning From Analgesia and Sedation in PICU (TIP-15-01)
A Phase 2 study testing Dexmedetomidine in people with Withdrawal Syndrome, run by IRCCS Azienda Ospedaliero-Universitaria di Bologna at 1 site in Italy.
Trial summary
This interventional study evaluates the efficacy of dexmedetomidine during weaning from analgesic and sedative drugs in reducing the occurrence of the withdrawal syndrome in PICU. All enrolled patients will undergo the same weaning regimen one half will receive dexmedetomidine while the other will receive a placebo. Read more about this study
- Who is it for?
- Ages 7 days to 18 years
- Conditions the study is for
- Withdrawal Syndrome
- What is being tested?
- Dexmedetomidine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 1 siteItaly
- Study dates
- 30 Aug 2018to 18 Jan 2020
- Phase
- Phase 2
- 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 7 days to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Continuous analgesic and sedative endovenous treatment for at least 5 days
- Invasive or non-invasive mechanical ventilation
- Clinical conditions that allow by clinical judgment the start of analgosedation weaning
- Post-natal age ≥ 7 days and PMA beyond the 37 weeks
- Written informed consent obtained
Who cannot join
- Hemodynamic instability
- Cardiac bundle-branch block of 2 or 3 degree
- Hypersensitivity to the alpha-agonists
- Persistent fever of unknown origin or sensitivity to malignant hyperthermia
- Use of alpha-agonist (clonidine or dexmedetomidine) in the last 30 days
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Efficacy and Safety of Dexmedetomidine During Weaning From Analgesia and Sedation in Pediatric Intensive Care Unit. A Multicenter, Double-blind, Randomized Controlled Trial.
This interventional study evaluates the efficacy of dexmedetomidine during weaning from analgesic and sedative drugs in reducing the occurrence of the withdrawal syndrome in PICU. All enrolled patients will undergo the same weaning regimen one half will receive dexmedetomidine while the other will receive a placebo.
Read the detailed description
Children admitted to PICU need of analgesic and sedative drugs. Prolonged treatment can lead to undesirable effects as dependence and tolerance. Patients that have developed dependence may develop the withdrawal syndrome (WS) during the analgesics and sedatives weaning process.
Withdrawal symptoms are due to central nervous system excitement, gastrointestinal disturbance, and sympathetic system activation. The incidence of withdrawal syndrome is variable between 17 and 57% a recent study reported an incidence of 64.6% of WS in Italian PICUs. The prevention strategies are addressed to the restriction of drug exposure and to the gradual tapering of infusion. However, these strategies have weak evidence of effectiveness. In this study, the investigators hypothesize that dexmedetomidine may be useful and effective during the weaning of analgosedation drugs in PICU, in preventing the withdrawal syndrome. The primary aim of the study is to evaluate the efficacy of dexmedetomidine in reducing the occurrence of the WS. Secondary aims are to evaluate the dexmedetomidine safety during the weaning, the effective dose range, and the efficacy in reducing the duration of the weaning, of the mechanical ventilation, and of the length of PICU stay. Efficacy will be compared among pediatric age groups, gender, race, Pediatric Index of Mortality (PIM3) score, and length of the analgosedation treatment.
Patients admitted to the PICU that meets the inclusion criteria, will be randomly assigned to one of the two treatment groups: treatment A (dexmedetomidine) or treatment B (placebo).
Twenty-four hours before the start of the weaning an intravenous infusion of dexmedetomidine/placebo will start. After 24 hours of dexmedetomidine infusion, the weaning regimen will begin following the subsequent indications: 10% reduction of the dose every 12 hours. The withdrawal assessment tool version 1 (WAT-1) is the selected scale to evaluate the occurrence of the WS. Patients with a score of WAT-1 <3 continue the weaning regimen. Patients with a score ≥3 increase the dose of dexmedetomidine/placebo until the next WAT-1 score control and temporarily stop the planned 10% dose reduction. If the next WAT-1 score decreased by at least 1 point from the previous score, the weaning program restarted (10% reduction) without further changes in the dose of dexmedetomidine/placebo until the subsequent score. The 'acute withdrawal crisis' will be treated with a rescue dose of the opioid and/or benzodiazepine in use repeatable until resolution of the crisis. Once analgesics and sedatives weaning is complete, dexmedetomidine will gradually discontinue. Five days after discharge from PICU, a follow-up visit will be performed.
The sample size estimate is 80 participants for each of the two groups for a total of 160 patients recruited within a period of two years.
- Conditions
- Withdrawal Syndrome
- Being tested
- Dexmedetomidine, Placebo
- Keywords
- pediatrics, dexmedetomidine, analgesia, sedation, pediatric intensive care unit, abstinence syndrome, assessment tool
- Medical subject headings
- Substance Withdrawal Syndrome, Agnosia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexmedetomidineDrug
Also called Dexdor, Precedex
intravenous infusion
PlaceboDrug
Also called physiological saline solution
intravenous infusion of physiological saline solution to mimic dexmedetomidine infusion
| Study group | Role | What they receive |
|---|---|---|
| Dexmedetomidine | Experimental | Dexmedetomidine 100 mcg/ml concentrate solution. Continuous iv infusion. Start dose 0.4 mcg/kg/h, increases by 0.2 mcg/kg/h until 0.8 mcg/kg/h (half dose for neonates). If withdrawal symptoms appear the dose can be increased to a maximum of 1.4 mcg/Kg/h. Receives: Drug: Dexmedetomidine |
| Placebo | Placebo comparator | saline solution for IV infusion. The administration of infusion will follow the experimental drug. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Withdrawal Assessment Tool (WAT-1) scale
WAT-1 score recorded every 12 hours.The score ranges from 0 to 12, a score ≥3 indicates the presence of signs/symptoms of withdrawal.
Measured: time 0 start dexmedetomidine and every 12 hours post-start dexmedetomidine for 7 days
Secondary outcomes (3)
Change in heart rate
changes in heart rate will be recorded when their value differs more than 20% by the patient's baseline values.
Measured: 0,1, 2, 12, 24 hours post-start dexmedetomidine and then every 12 hours for 7 days
Change in Systolic Blood Pressure
changes in Systolic Blood Pressure will be recorded when their value differs more than 20% by the patient's baseline values.
Measured: 0,1, 2, 12, 24 hours post-start dexmedetomidine and then every 12 hours for 7 days
Change in Diastolic Blood Pressure
changes in Diastolic Blood Pressure will be recorded when their value differs more than 20% by the patient's baseline values.
Measured: 0,1, 2, 12, 24 hours post-start dexmedetomidine and then every 12 hours for 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2018
- Study start30 Aug 2018
- Primary completion18 Jan 2020
- Study completion18 Jan 2020
Why it stopped: futility reasons
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Withdrawal SyndromeStudies of the same condition, open and under way.
- More trials run by IRCCS Azienda Ospedaliero-Universitaria di BolognaThe 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Azienda Ospedaliera di Padova, Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Responsible party
- Principal investigator, Maria Cristina Mondardini, IRCCS Azienda Ospedaliero-Universitaria di Bologna
- Investigators
- Maria C. Mondardini, MD, Study chair, Azienda Ospedaliero Universitaria di Bologna Policlinico S.Orsola-Malpighi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03645603
- Sponsor's protocol ID
- EudraCT 2015-002114-80 OsSC
- Acronym
- TIP-15-01
- Status last verified
- Oct 2021
- First submitted
- 17 Aug 2018
- Last updated
- 2 Nov 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Amigoni A, Mondardini MC, Vittadello I, Zaglia F, Rossetti E, Vitale F, Ferrario S, Savron F, Coffaro G, Brugnaro L, Amato R, Wolfler A, Franck LS; Network of Paediatric Intensive Care Unit Study Group (TIPNet). Withdrawal Assessment Tool-1 Monitoring in PICU: A Multicenter Study on Iatrogenic Withdrawal Syndrome. Pediatr Crit Care Med. 2017 Feb;18(2):e86-e91. doi: 10.1097/PCC.0000000000001054.
PubMed 28157809Mondardini MC, Daverio M, Caramelli F, Conti G, Zaggia C, Lazzarini R, Muscheri L, Azzolina D, Gregori D, Sperotto F, Amigoni A. Dexmedetomidine for prevention of opioid/benzodiazepine withdrawal syndrome in pediatric intensive care unit: Interim analysis of a randomized controlled trial. Pharmacotherapy. 2022 Feb;42(2):145-153. doi: 10.1002/phar.2654. Epub 2021 Dec 21.
PubMed 34882826Mondardini MC, Sperotto F, Daverio M, Caramelli F, Gregori D, Caligiuri MF, Vitale F, Cecini MT, Piastra M, Mancino A, Pettenazzo A, Conti G, Amigoni A. Efficacy and safety of dexmedetomidine for prevention of withdrawal syndrome in the pediatric intensive care unit: protocol for an adaptive, multicenter, randomized, double-blind, placebo-controlled, non-profit clinical trial. Trials. 2019 Dec 11;20(1):710. doi: 10.1186/s13063-019-3793-6.
PubMed 31829274
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Dexmedetomidine During Weaning From Analgesia and Sedation in Pediatric Intensive Care Unit. A Multicenter, Double-blind, Randomized Controlled Trial.
- ClinicalTrials.gov ID
- NCT03645603
- Acronym / sponsor ID
- TIP-15-01 / EudraCT 2015-002114-80 OsSC
- Conditions
- Withdrawal Syndrome
- Keywords
- pediatrics, dexmedetomidine, analgesia, sedation, pediatric intensive care unit, abstinence syndrome, assessment tool
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: futility reasons
- Enrolment
- 45 participants (actual)
- Lead sponsor
- IRCCS Azienda Ospedaliero-Universitaria di BolognaUniversity, hospital or other
- Collaborators
- Azienda Ospedaliera di Padova, Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Study start
- 30 Aug 2018 (actual)
- Primary completion
- 18 Jan 2020 (actual)
- Study completion
- 18 Jan 2020 (actual)
- First posted
- 24 Aug 2018 (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.
This interventional study evaluates the efficacy of dexmedetomidine during weaning from analgesic and sedative drugs in reducing the occurrence of the withdrawal syndrome in PICU. All enrolled patients will undergo the same weaning regimen one half will receive dexmedetomidine while the other will receive a placebo.
Detailed description
Children admitted to PICU need of analgesic and sedative drugs. Prolonged treatment can lead to undesirable effects as dependence and tolerance. Patients that have developed dependence may develop the withdrawal syndrome (WS) during the analgesics and sedatives weaning process.
Withdrawal symptoms are due to central nervous system excitement, gastrointestinal disturbance, and sympathetic system activation. The incidence of withdrawal syndrome is variable between 17 and 57% a recent study reported an incidence of 64.6% of WS in Italian PICUs. The prevention strategies are addressed to the restriction of drug exposure and to the gradual tapering of infusion. However, these strategies have weak evidence of effectiveness. In this study, the investigators hypothesize that dexmedetomidine may be useful and effective during the weaning of analgosedation drugs in PICU, in preventing the withdrawal syndrome. The primary aim of the study is to evaluate the efficacy of dexmedetomidine in reducing the occurrence of the WS. Secondary aims are to evaluate the dexmedetomidine safety during the weaning, the effective dose range, and the efficacy in reducing the duration of the weaning, of the mechanical ventilation, and of the length of PICU stay. Efficacy will be compared among pediatric age groups, gender, race, Pediatric Index of Mortality (PIM3) score, and length of the analgosedation treatment.
Patients admitted to the PICU that meets the inclusion criteria, will be randomly assigned to one of the two treatment groups: treatment A (dexmedetomidine) or treatment B (placebo).
Twenty-four hours before the start of the weaning an intravenous infusion of dexmedetomidine/placebo will start. After 24 hours of dexmedetomidine infusion, the weaning regimen will begin following the subsequent indications: 10% reduction of the dose every 12 hours. The withdrawal assessment tool version 1 (WAT-1) is the selected scale to evaluate the occurrence of the WS. Patients with a score of WAT-1 <3 continue the weaning regimen. Patients with a score ≥3 increase the dose of dexmedetomidine/placebo until the next WAT-1 score control and temporarily stop the planned 10% dose reduction. If the next WAT-1 score decreased by at least 1 point from the previous score, the weaning program restarted (10% reduction) without further changes in the dose of dexmedetomidine/placebo until the subsequent score. The 'acute withdrawal crisis' will be treated with a rescue dose of the opioid and/or benzodiazepine in use repeatable until resolution of the crisis. Once analgesics and sedatives weaning is complete, dexmedetomidine will gradually discontinue. Five days after discharge from PICU, a follow-up visit will be performed.
The sample size estimate is 80 participants for each of the two groups for a total of 160 patients recruited within a period of two years.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dexmedetomidine | Experimental | Drug: DexmedetomidineDexmedetomidine 100 mcg/ml concentrate solution. Continuous iv infusion. Start dose 0.4 mcg/kg/h, increases by 0.2 mcg/kg/h until 0.8 mcg/kg/h (half dose for neonates). If withdrawal symptoms appear the dose can be increased to a maximum of 1.4 mcg/Kg/h. |
| Placebo | Placebo comparator | Drug: Placebosaline solution for IV infusion. The administration of infusion will follow the experimental drug. |
Who may qualify
- Ages
- 7 days to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- Continuous analgesic and sedative endovenous treatment for at least 5 days
- Invasive or non-invasive mechanical ventilation
- Clinical conditions that allow by clinical judgment the start of analgosedation weaning
- Post-natal age ≥ 7 days and PMA beyond the 37 weeks
- Written informed consent obtained
Key exclusion criteria (5 listed)
- Hemodynamic instability
- Cardiac bundle-branch block of 2 or 3 degree
- Hypersensitivity to the alpha-agonists
- Persistent fever of unknown origin or sensitivity to malignant hyperthermia
- Use of alpha-agonist (clonidine or dexmedetomidine) in the last 30 days
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 |
|---|---|---|
| DexmedetomidineAlso: Dexdor, Precedexintravenous infusion | Drug | Dexmedetomidine |
| PlaceboAlso: physiological saline solutionintravenous infusion of physiological saline solution to mimic dexmedetomidine infusion | Drug | Placebo |
Primary outcome
Change in Withdrawal Assessment Tool (WAT-1) scale
Time frame: time 0 start dexmedetomidine and every 12 hours post-start dexmedetomidine for 7 days
WAT-1 score recorded every 12 hours.The score ranges from 0 to 12, a score ≥3 indicates the presence of signs/symptoms of withdrawal.
3 secondary outcomes
Change in heart rate
Time frame: 0,1, 2, 12, 24 hours post-start dexmedetomidine and then every 12 hours for 7 days
Change in Systolic Blood Pressure
Time frame: 0,1, 2, 12, 24 hours post-start dexmedetomidine and then every 12 hours for 7 days
Change in Diastolic Blood Pressure
Time frame: 0,1, 2, 12, 24 hours post-start dexmedetomidine and then every 12 hours for 7 days
Results and safety
The study was stopped early (reason given: futility reasons). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2021.
- Results publication: PubMed 28157809Amigoni A, Mondardini MC, Vittadello I, Zaglia F, Rossetti E, Vitale F, Ferrario S, Savron F, Coffaro G, Brugnaro L, Amato R, Wolfler A, Franck LS; Network of Paediatric Intensive Care Unit Study Group (TIPNet). Withdrawal Assessment Tool-1 Monitoring in PICU: A Multicenter Study on Iatrogenic Withdrawal Syndrome. Pediatr Crit Care Med. 2017 Feb;18(2):e86-e91. doi: 10.1097/PCC.0000000000001054.
- Derived from this study: PubMed 34882826Mondardini MC, Daverio M, Caramelli F, Conti G, Zaggia C, Lazzarini R, Muscheri L, Azzolina D, Gregori D, Sperotto F, Amigoni A. Dexmedetomidine for prevention of opioid/benzodiazepine withdrawal syndrome in pediatric intensive care unit: Interim analysis of a randomized controlled trial. Pharmacotherapy. 2022 Feb;42(2):145-153. doi: 10.1002/phar.2654. Epub 2021 Dec 21.
- Derived from this study: PubMed 31829274Mondardini MC, Sperotto F, Daverio M, Caramelli F, Gregori D, Caligiuri MF, Vitale F, Cecini MT, Piastra M, Mancino A, Pettenazzo A, Conti G, Amigoni A. Efficacy and safety of dexmedetomidine for prevention of withdrawal syndrome in the pediatric intensive care unit: protocol for an adaptive, multicenter, randomized, double-blind, placebo-controlled, non-profit clinical trial. Trials. 2019 Dec 11;20(1):710. doi: 10.1186/s13063-019-3793-6.
- 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.
Maria C. Mondardini, MD study chair
Azienda Ospedaliero Universitaria di Bologna Policlinico S.Orsola-Malpighi
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dexmedetomidine in people with Withdrawal Syndrome, run by IRCCS Azienda Ospedaliero-Universitaria di Bologna at 1 site in Italy.
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 5 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: stopped early, as of the sponsor's last update on 2 Nov 2021. 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 Italy. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 was stopped early (reason given: futility reasons). Results are not available in the source record.
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?
Change in Withdrawal Assessment Tool (WAT-1) scale (time frame: time 0 start dexmedetomidine and every 12 hours post-start dexmedetomidine for 7 days). 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 NCT03645603, which also lists 3 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 2 Nov 2021; AzTrials last refreshed its copy on 8 Nov 2026.