DeliriumPhase 2NCT04382170
Dexmedetomidine Sublingual Film for the Management of Agitation in Delirium: Safety and Preliminary Efficacy
A Phase 2 study testing Dexmedetomidine sublingual film in people with Delirium, run by Jeff C. Huffman, MD.
Trial summary
The investigator will examine the safety, tolerability, optimal dose, and preliminary efficacy of dexmedetomidine sublingual film in a randomized, double-blind, controlled trial in 40 hospitalized patients with hyperactive delirium (i.e., delirium with agitation) in the Intensive Care Unit (ICU) setting. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Delirium
- What is being tested?
- Dexmedetomidine sublingual film
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jun 2020to Jun 2021
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults hospitalized on a medical or surgical intensive care unit at MGH
- Diagnosis of delirium, assessed according to DSM-5 criteria (DSM-5)
- Body mass index (BMI) between 18 and 30 kg/m2, inclusive, at screening
- Weight at least 60 kg (132 pounds), at screening
- In the opinion of the study and clinical teams, sufficiently physically healthy to receive dexmedetomidine sublingual film
Who cannot join
- Per medical record or team report, diagnoses of:
- Dementia
- Significant traumatic brain injury
- History of stroke, with persistent neurologic deficits
- Presence of any of the following cardiovascular comorbidities
- Sick sinus syndrome
Show all 21Show fewer
- A resting heart rate of < 55 beats per minutes or systolic blood pressure (BP) <100 mmHg or >160 mmHg or diastolic BP <70 mmHg or ˃ 95 mmHg at enrollment and prior to dosing.
- Evidence of cardiac ischemia on a 12-lead electrocardiogram (ECG)
- Corrected QT interval of > 450 msec
- Presence of a permanent pacemaker device
- Per medical record (notes, current medications, flowsheets):
- Second degree (or greater) Atrioventricular (AV) block without a pacemaker
- Known allergy or adverse reaction to dexmedetomidine
- Current use of dexmedetomidine
- Inability to take sublingual dexmedetomidine due to severe agitation, neurological impairment, nil per os (NPO) status, or other cause.
- Hepatic impairment (liver function tests > 3 times the upper limit of normal)
- Severe renal impairment (glomerular filtration rate (GFR) < 30 ml/min or on dialysis)
- Weight < 60 kg
- Pregnancy (in women; tested with serum or urine human chorionic gonadotropin [hCG])
- Non-fluency in English
- Prior enrollment in the study, with receipt of study medication, during the current or a previous hospitalization
About this study
The investigator will examine the safety, tolerability, optimal dose, and preliminary efficacy of dexmedetomidine sublingual film in a randomized, double-blind, controlled trial in 40 hospitalized patients with hyperactive delirium (i.e., delirium with agitation) in the Intensive Care Unit (ICU) setting.
Specific Aim #1 (safety and tolerability): To examine the incidence of cardiovascular and other side effects following the administration of dexmedetomidine sublingual film in patients hospitalized in the ICU with delirium and agitation in a randomized, double-blind trial (total N=80 patients with delirium [with or without agitation], with a goal of administering dexmedetomidine to at least 40 participants with agitation).
Read more
Hypothesis: Dexmedetomidine sublingual film will be associated with hypotension and/or bradycardia requiring clinical intervention in ≤ 20% (8 of 40) participants. Dexmedetomidine will not be associated with QTc prolongation or non-cardiac adverse events.
Specific Aim #2 (preliminary efficacy): To examine the impact of dexmedetomidine sublingual film on agitation and delirium severity.
Hypothesis: Dexmedetomidine will lead to reductions in agitation and delirium severity during the follow-up period (co-primary endpoints = 1 and 2 hours post-administration).
Specific Aim #3 (optimal dosing): To identify the minimum dose that is effective at reducing agitation and delirium severity without causing significant side effects.
Hypothesis: Participants receiving doses of 60 mcg of dexmedetomidine will have a faster time to a reduction in agitation and greater reductions in delirium severity than participants receiving 20 mcg of dexmedetomidine.
Read the detailed description
Study Intervention
Participants will be randomized to receive either 20 mcg or 60 mcg of dexmedetomidine sublingually. Participants will receive repeat dosing every 30 minutes for up to three additional doses, leading to maximum doses of 80 mcg and 240 mcg, respectively. Both investigators and clinicians will be blind to the participant's group, with only the study pharmacist aware of the dose of medication on the films.
Baseline monitoring: Following enrollment, the study team will record baseline measures of heart rate, blood pressure, and oxygen saturation. An electrocardiogram (ECG) will be performed, and agitation and delirium severity will be measured.
Medication administration: Dexmedetomidine sublingual film will be administered by the study physician or study nurse as per the manufacturer's instructions. Dexmedetomidine administration will be repeated every 30 minutes if the participant continues to have agitation and does not meet any cardiovascular stopping criteria.
Monitoring for side effects: Heart rate, blood pressure, oxygen saturation, use of supplemental oxygen, and use of pressors will be monitored continuously and recorded every 30 minutes for the 6 hours following the initial medication administration (baseline; Time 0). An ECG will be performed at 1.5, 3, 4.5, and 6 hours, and QTc will be calculated using the Fridericia formula. Study staff will also monitor the participant and speak with nursing staff at 6 hours to assess for any other side effects/complaints the patient may have had during the time since medication administration.
Monitoring of agitation and delirium severity: Agitation will be measured every 30 minutes and delirium severity at hours 1, 2, 3, 4, and 6.
Study Endpoints
Safety and Tolerability (Aim #1) The investigators will examine changes in heart rate, blood pressure, oxygen saturation, and QTc interval from baseline to the follow-up timepoints, as well as the incidence of self-reported and clinician-reported side effects during the 6-hour post-medication interval. They also will record the total dosage of medication each participant received and examine whether medication dose was associated with the incidence of side effects.
Preliminary Efficacy (Aim #2) The investigators will assess changes in agitation and delirium from baseline to the follow-up timepoints. One and two hours following medication administration will be considered the co-primary timepoints for these efficacy measures. They also will record the total dosage of medication each participant received and examine whether medication dose was associated with a reduction in agitation and delirium severity.
Minimum Dose of Administration (Aim #3) The investigators will measure the amount of time from the initial dexmedetomidine administration until agitation resolves. Then, they will compare between-group differences in time to agitation resolution, changes in agitation and delirium severity, and the incidence of side effects. The optimal dose will be chosen based on the dose that leads to the quickest resolution of agitation without leading to clinically significant side effects.
- Conditions
- Delirium
- Being tested
- Dexmedetomidine sublingual film
- Keywords
- agitation, delirium, dexmedetomidine
- Medical subject headings
- Delirium, Psychomotor Agitation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dexmedetomidine sublingual filmDrug
Also called Precedex
Dexmedetomidine sublingual film for the management of agitation in hospitalized patients with delirium.
| Study group | Role | What they receive |
|---|---|---|
| 20 mcg | Active comparator | Participants randomized to the 20mcg group will receive 20mcg of dexmedetomidine sublingual film every 30 minutes, if they continue to have agitation and do not meet any cardiovascular stopping criteria. The maximum dosing for this arm is 80mcg. Receives: Drug: Dexmedetomidine sublingual film |
| 60 mcg | Experimental | Participants randomized to the 60mcg group will receive 60mcg of dexmedetomidine sublingual film every 30 minutes, if they continue to have agitation and do not meet any cardiovascular stopping criteria. The maximum dosing for this arm is 240mcg. Receives: Drug: Dexmedetomidine sublingual film |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Heart Rate
Heart rate will be assessed participant's flowsheet or using the telemetry monitor for the 6 hours following the initial medication administration.
Measured: Baseline, Medication Administration (Hour 0), Hour 0.5, Hour 1, Hour 1.5, Hour 2, Hour 2.5, Hour 3, Hour 3.5, Hour 4, Hour 4.5, Hour 5, Hour 5.5, Hour 6
Change in Blood Pressure
Blood pressure will be assessed participant's flowsheet or using the telemetry monitor/automated blood pressure cuff for the 6 hours following the initial medication administration.
Measured: Baseline, Medication Administration (Hour 0), Hour 0.5, Hour 1, Hour 1.5, Hour 2, Hour 2.5, Hour 3, Hour 3.5, Hour 4, Hour 4.5, Hour 5, Hour 5.5, Hour 6
Change in Oxygen Saturation
Oxygen saturation will be assessed participant's Epic flowsheet or using the telemetry monitor/pulse oximter for the 6 hours following the initial medication administration.
Measured: Baseline, Medication Administration (Hour 0), Hour 0.5, Hour 1, Hour 1.5, Hour 2, Hour 2.5, Hour 3, Hour 3.5, Hour 4, Hour 4.5, Hour 5, Hour 5.5, Hour 6
Change in QTc Interval
An ECG will be performed intermittently over the 6 hour monitoring period, and QTc will be calculated using the Fridericia formula.
Measured: Baseline, Hour 1.5, Hour 3, Hour 4.5, Hour 6
Self-reported Side Effects
Incidence of side effects reported for dexmedetomidine in post-marketing surveillance
Measured: Hour 6
Secondary outcomes (3)
Change in Agitation
Agitation will be measured by the Richmond Agitation-Sedation Scale (RASS). RASS is a 10-point scale ranging from -5 to +4, with a more positive score indicating increased agitation.
Measured: Baseline, Hour 0.5, Hour 1, Hour 1.5, Hour 2, Hour 2.5, Hour 3, Hour 3.5, Hour 4, Hour 4.5, Hour 6
Change in Delirium Severity
Delirium severity will be measured by the Delirium Rating Scale-revised-98 (DRS-R-98). The maximum possible score for severity items is 39, while the maximum total score is 46. Higher scores indicate more severe delirium; score of 0 indicates no delirium.
Measured: Baseline, Hour 1, Hour 2, Hour 3, Hour 4, Hour 6
Time to resolution of agitation
Amount of time from the initial dexmedetomidine administration until agitation resolves measured by RASS score < 1
Measured: Hour 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2020
- Study startJun 2020 (estimated)
- Primary completionJun 2021 (estimated)
- Study completionJun 2021 (estimated)
Why it stopped: The study sponsor decided not to perform this study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DeliriumStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This study will be a randomized, controlled, 2-arm, double-blinded trial.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jeff C. Huffman, MD
- Sponsor type
- University, hospital or other
- Collaborators
- BioXcel Therapeutics Inc
- Responsible party
- Sponsor-investigator, Jeff C. Huffman, MD, Massachusetts General Hospital
- Investigators
- Jeff C Huffman, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04382170
- Sponsor's protocol ID
- 2019P002353
- Status last verified
- May 2024
- First submitted
- 25 Apr 2020
- Last updated
- 13 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dexmedetomidine Sublingual Film for the Management of Agitation in Delirium: Safety and Preliminary Efficacy
- ClinicalTrials.gov ID
- NCT04382170
- Acronym / sponsor ID
- 2019P002353
- Conditions
- Delirium
- Keywords
- agitation, delirium, dexmedetomidine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The study sponsor decided not to perform this study.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Jeff C. Huffman, MDUniversity, hospital or other
- Collaborators
- BioXcel Therapeutics Inc
- Study start
- Jun 2020 (estimated)
- Primary completion
- Jun 2021 (estimated)
- Study completion
- Jun 2021 (estimated)
- First posted
- 11 May 2020 (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.
The investigator will examine the safety, tolerability, optimal dose, and preliminary efficacy of dexmedetomidine sublingual film in a randomized, double-blind, controlled trial in 40 hospitalized patients with hyperactive delirium (i.e., delirium with agitation) in the Intensive Care Unit (ICU) setting.
Specific Aim #1 (safety and tolerability): To examine the incidence of cardiovascular and other side effects following the administration of dexmedetomidine sublingual film in patients hospitalized in the ICU with delirium and agitation in a randomized, double-blind trial (total N=80 patients with delirium [with or without agitation], with a goal of administering dexmedetomidine to at least 40 participants with agitation).
Hypothesis: Dexmedetomidine sublingual film will be associated with hypotension and/or bradycardia requiring clinical intervention in ≤ 20% (8 of 40) participants. Dexmedetomidine will not be associated with QTc prolongation or non-cardiac adverse events.
Specific Aim #2 (preliminary efficacy): To examine the impact of dexmedetomidine sublingual film on agitation and delirium severity.
Hypothesis: Dexmedetomidine will lead to reductions in agitation and delirium severity during the follow-up period (co-primary endpoints = 1 and 2 hours post-administration).
Specific Aim #3 (optimal dosing): To identify the minimum dose that is effective at reducing agitation and delirium severity without causing significant side effects.
Hypothesis: Participants receiving doses of 60 mcg of dexmedetomidine will have a faster time to a reduction in agitation and greater reductions in delirium severity than participants receiving 20 mcg of dexmedetomidine.
Detailed description
Study Intervention
Participants will be randomized to receive either 20 mcg or 60 mcg of dexmedetomidine sublingually. Participants will receive repeat dosing every 30 minutes for up to three additional doses, leading to maximum doses of 80 mcg and 240 mcg, respectively. Both investigators and clinicians will be blind to the participant's group, with only the study pharmacist aware of the dose of medication on the films.
Baseline monitoring: Following enrollment, the study team will record baseline measures of heart rate, blood pressure, and oxygen saturation. An electrocardiogram (ECG) will be performed, and agitation and delirium severity will be measured.
Medication administration: Dexmedetomidine sublingual film will be administered by the study physician or study nurse as per the manufacturer's instructions. Dexmedetomidine administration will be repeated every 30 minutes if the participant continues to have agitation and does not meet any cardiovascular stopping criteria.
Monitoring for side effects: Heart rate, blood pressure, oxygen saturation, use of supplemental oxygen, and use of pressors will be monitored continuously and recorded every 30 minutes for the 6 hours following the initial medication administration (baseline; Time 0). An ECG will be performed at 1.5, 3, 4.5, and 6 hours, and QTc will be calculated using the Fridericia formula. Study staff will also monitor the participant and speak with nursing staff at 6 hours to assess for any other side effects/complaints the patient may have had during the time since medication administration.
Monitoring of agitation and delirium severity: Agitation will be measured every 30 minutes and delirium severity at hours 1, 2, 3, 4, and 6.
Study Endpoints
Safety and Tolerability (Aim #1) The investigators will examine changes in heart rate, blood pressure, oxygen saturation, and QTc interval from baseline to the follow-up timepoints, as well as the incidence of self-reported and clinician-reported side effects during the 6-hour post-medication interval. They also will record the total dosage of medication each participant received and examine whether medication dose was associated with the incidence of side effects.
Preliminary Efficacy (Aim #2) The investigators will assess changes in agitation and delirium from baseline to the follow-up timepoints. One and two hours following medication administration will be considered the co-primary timepoints for these efficacy measures. They also will record the total dosage of medication each participant received and examine whether medication dose was associated with a reduction in agitation and delirium severity.
Minimum Dose of Administration (Aim #3) The investigators will measure the amount of time from the initial dexmedetomidine administration until agitation resolves. Then, they will compare between-group differences in time to agitation resolution, changes in agitation and delirium severity, and the incidence of side effects. The optimal dose will be chosen based on the dose that leads to the quickest resolution of agitation without leading to clinically significant side effects.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This study will be a randomized, controlled, 2-arm, double-blinded trial.
| Arm | Type | Receives |
|---|---|---|
| 20 mcg | Active comparator | Drug: Dexmedetomidine sublingual filmParticipants randomized to the 20mcg group will receive 20mcg of dexmedetomidine sublingual film every 30 minutes, if they continue to have agitation and do not meet any cardiovascular stopping criteria. The maximum dosing for this arm is 80mcg. |
| 60 mcg | Experimental | Drug: Dexmedetomidine sublingual filmParticipants randomized to the 60mcg group will receive 60mcg of dexmedetomidine sublingual film every 30 minutes, if they continue to have agitation and do not meet any cardiovascular stopping criteria. The maximum dosing for this arm is 240mcg. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adults hospitalized on a medical or surgical intensive care unit at MGH
- Diagnosis of delirium, assessed according to DSM-5 criteria (DSM-5)
- Body mass index (BMI) between 18 and 30 kg/m2, inclusive, at screening
- Weight at least 60 kg (132 pounds), at screening
- In the opinion of the study and clinical teams, sufficiently physically healthy to receive dexmedetomidine sublingual film
Key exclusion criteria (21 listed)
- Per medical record or team report, diagnoses of:
- Presence of any of the following cardiovascular comorbidities
- Per medical record (notes, current medications, flowsheets):
- Inability to take sublingual dexmedetomidine due to severe agitation, neurological impairment, nil per os (NPO) status, or other cause.
- Hepatic impairment (liver function tests > 3 times the upper limit of normal)
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 |
|---|---|---|
| Dexmedetomidine sublingual filmAlso: PrecedexDexmedetomidine sublingual film for the management of agitation in hospitalized patients with delirium. | Drug | 20 mcg, 60 mcg |
Primary outcome
Change in Heart Rate
Time frame: Baseline, Medication Administration (Hour 0), Hour 0.5, Hour 1, Hour 1.5, Hour 2, Hour 2.5, Hour 3, Hour 3.5, Hour 4, Hour 4.5, Hour 5, Hour 5.5, Hour 6
Heart rate will be assessed participant's flowsheet or using the telemetry monitor for the 6 hours following the initial medication administration.
Change in Blood Pressure
Time frame: Baseline, Medication Administration (Hour 0), Hour 0.5, Hour 1, Hour 1.5, Hour 2, Hour 2.5, Hour 3, Hour 3.5, Hour 4, Hour 4.5, Hour 5, Hour 5.5, Hour 6
Blood pressure will be assessed participant's flowsheet or using the telemetry monitor/automated blood pressure cuff for the 6 hours following the initial medication administration.
Change in Oxygen Saturation
Time frame: Baseline, Medication Administration (Hour 0), Hour 0.5, Hour 1, Hour 1.5, Hour 2, Hour 2.5, Hour 3, Hour 3.5, Hour 4, Hour 4.5, Hour 5, Hour 5.5, Hour 6
Oxygen saturation will be assessed participant's Epic flowsheet or using the telemetry monitor/pulse oximter for the 6 hours following the initial medication administration.
Change in QTc Interval
Time frame: Baseline, Hour 1.5, Hour 3, Hour 4.5, Hour 6
An ECG will be performed intermittently over the 6 hour monitoring period, and QTc will be calculated using the Fridericia formula.
Self-reported Side Effects
Time frame: Hour 6
Incidence of side effects reported for dexmedetomidine in post-marketing surveillance
3 secondary outcomes
Change in Agitation
Time frame: Baseline, Hour 0.5, Hour 1, Hour 1.5, Hour 2, Hour 2.5, Hour 3, Hour 3.5, Hour 4, Hour 4.5, Hour 6
Change in Delirium Severity
Time frame: Baseline, Hour 1, Hour 2, Hour 3, Hour 4, Hour 6
Time to resolution of agitation
Time frame: Hour 6
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2024.
- 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.
Jeff C Huffman, MD principal investigator
Massachusetts General Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dexmedetomidine sublingual film in people with Delirium, run by Jeff C. Huffman, MD.
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 21 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: withdrawn, as of the sponsor's last update on 13 May 2024. Status can change between updates, so confirm with the study contact before making plans.
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.
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 withdrawn before enrolling participants, so there are no results.
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 Heart Rate (time frame: Baseline, Medication Administration (Hour 0), Hour 0.5, Hour 1, Hour 1.5, Hour 2, Hour 2.5, Hour 3, Hour 3.5, Hour 4, Hour 4.5, Hour 5, Hour 5.5, Hour 6). The study lists 5 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 13 May 2024.