DeliriumPhase 4NCT02118688
Efficacy and Safety of Risperidone and Trazodone Monotherapy and Combination Therapy in Critically Ill Patients With Delirium
A Phase 4 study testing Risperidone and Trazodone in people with Delirium and Agitation, run by Rochester General Hospital at 1 site in United States.
Trial summary
The purpose of this randomized clinical trial is to determine whether risperidone alone, trazodone alone, or a combination of risperidone and trazodone is superior for the treatment of ICU acquired delirium. Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- Risperidone and Trazodone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2011to Mar 2016
- Phase
- Phase 4
- 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
- Age greater than 18 years old who are admitted for more than 24 hours in the MICU or SICU
- Patients diagnosed with delirium by primary team (screened positive for delirium using the CAM-ICU or with clinical manifestations of delirium)
- Patients have an order for as-needed haloperidol or have received a one-time dose of haloperidol within 24 hours of randomization
- Patients must be tolerating enteral feeding (greater than 20 mL/hour for more than 12 hours)
Who cannot join
- Patients who are unlikely to survive 24 hours after admission to the ICU
- Patients who are admitted with a primary neurological condition or injury (i.e. stroke, active seizures, prolonged coma, overdose)
- Patients who can not actively participate in delirium assessment
- Patients actively withdrawing from alcohol or narcotics
- Patients who were treated with any antipsychotic or trazodone within 30 days prior to ICU admission
- Patients with a marked baseline prolongation of the QTc interval (repeated demonstration of QTc interval greater 500 milliseconds (msec))
Show all 13Show fewer
- Patients with a history of Torsades de Pointes
- Patients with current treatment with an agent having either the potential to affect or increase the risk of QTc prolongation (e.g. erythromycin, any class Ia, Ic, or III antiarrhythmics)
- Patients being treated with a neuromuscular blocker
- Patients in whom haloperidol, risperidone, or trazodone is contraindicated
- Pregnant patients or patients who are breast-feeding
- Patients with a modified Blessed dementia rating scale score ≥4 or an Informant Questionnaire of Cognitive Dysfunction in the Elderly Score ≥4
- Patients in which informed consent can not be obtained from the legally authorized representative
Trial locations and contacts
1 site in 1 country.
United States1 site
Rochester General Hospital
Rochester, New York, 14621
About this study
Official title: Efficacy and Safety of Risperidone and Trazodone Monotherapy and Combination Therapy in Critically Ill Patients With Delirium: A Four-arm Prospective, Randomized, Double-blind, Placebo-controlled Pilot Study
The purpose of this randomized clinical trial is to determine whether risperidone alone, trazodone alone, or a combination of risperidone and trazodone is superior for the treatment of ICU acquired delirium. The hypothesis is that combination therapy is superior to either agent alone in treating ICU acquired delirium and sustaining delirium free time.
Read the detailed description
Delirium is defined as a disturbance of consciousness characterized by an acute onset of impaired cognitive function. Although delirium is thought to be common in the Intensive Care Unit (ICU) there are few studies that have evaluated its incidences, risks and outcomes. It has been associated with increased morbidity, and mortality and increased cost to the healthcare system. In addition to the uncertainty of the incidence of ICU delirium, there is a lack of information about the effects that certain pharmacological treatments have on delirious patients.
The rationale for this study is to evaluate the efficacy and safety of risperidone alone, trazodone alone, and risperidone plus trazodone for the treatment of delirium in critically ill patients when compared to placebo.
- Being tested
- Risperidone, Trazodone, Placebo
- 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.
RisperidoneDrug
TrazodoneDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo
* Placebo suspension administered PO/NG/FT q12h to mimic risperidone
* Placebo suspension administered PO/NG/FT q8h to mimic trazodone Receives: Drug: Placebo |
| Risperidone alone | Active comparator | Drug: Risperidone
* Initiate risperidone at 1 mg PO/NG/FT q12h
* Risperidone dose can be titrated upwards every 24 hours by increments of 0.5 mg per dose
* Maximum risperidone daily dose of 6 mg per day (3 mg every 12 hours) Receives: Drug: Risperidone; Drug: Placebo |
| Trazodone alone | Active comparator | Drug: Trazodone
* Initiate trazodone dosing at 50 mg PO/NG/FT q8h
* Trazodone dose can be titrated upwards every 24 hours by 25 mg per dose
* Maximum trazodone daily dose 600 mg per day (200 mg every 8 hours) Receives: Drug: Trazodone; Drug: Placebo |
| Risperidone and Trazodone combination | Active comparator | Drug: Risperidone
* Initiate risperidone at 1 mg PO/NG/FT q12h
* Risperidone dose can be titrated upwards every 24 hours by increments of 0.5 mg per dose
* Maximum risperidone daily dose of 6 mg per day (3 mg every 12 hours)
Drug: Trazodone
* Initiate risperidone at 1 mg PO/NG/FT q12h
* Risperidone dose can be titrated upwards every 24 hours by increments of 0.5 mg per dose
* Maximum risperidone daily dose of 6 mg per day (3 mg every 12 hours) Receives: Drug: Risperidone; Drug: Trazodone |
What is being measured
The primary outcome is the main question the study is designed to answer.
The number of days patients are without delirium during the study period (delirium-free days)
The number of days patients are without delirium during the study period (delirium-free days)
Measured: Every 24 hours (up to 14 days)
Secondary outcomes (12)
Daily prevalence of delirium as indicated by a positive Confusion Assessment Method in the ICU (CAM-ICU)
Measured: Every 24 hours (up to 14 days)
Resolution of delirium as indicated by a negative Confusion Assessment Method in the ICU (CAM-ICU) for more than 24 hours
Measured: Every 24 hours (up to 14 days)
The number of patients who require rescue medications, the type of rescue medications utilized, and the amount of rescue medications per day
Measured: Every 24 hours (up to 14 days)
The number of patients who receive sedative agents, amount of midazolam equivalents per day, and the number of days in which patients receive a sedative agent
Measured: Every 24 hours (up to 14 days)
The number of patients who receive pain medications, amount of fentanyl equivalents per day, and the number of days in which patients receive a pain medication
Measured: Every 24 hours (up to 24 hours)
The number of hours spent agitated (RASS score between +4 and +2) as a percent of the time that the study drug was administered
Measured: Every 24 hours (up to 14 days)
The number of hours spent excessively sedated or in a coma state (RASS score between -4 to -5) as a percent of the time that the study drug was administered
Measured: Every 24 hours (up to 14 days)
The duration of mechanical ventilation from initial intubation to extubation as long as the patient remained extubated for more than 48 hours.
Measured: Time (hours) from initial intubation to extubation (as long as patient not reintubated within 48 hours)
The number of days that the patients were alive and breathing without assistance during the study period (ventilator-free days)
Measured: Time (days) from extubation to patient discharge (as long as patient not reintubated within 48 hours)
The number of episodes and number of patients who experience clinically significant QTc prolongation (≥ 500 msec or an increase of more than 60 msec from baseline)
Measured: QTc interval evaluated q12h during period of study drug administration (up to 14 days)
The number of episodes and number of patients who experience clinically significant extrapyramidal effects (as evidenced by a positive Simpson-Angus Scale Score)
Measured: Extrapyramidal effects evaluated by bedside nurse q12h during period of study drug administration (up to 14 days). Investigator will confirm RN suspicion of extrapyramidal effects using Simpson-Angus Score.
All-cause mortality and 28-day mortality
Measured: At 14 and 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2014 (estimated)
- Study startMar 2011
- Primary completionMar 2016
- Study completionMar 2016
Why it stopped: Lack of enrollment
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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rochester General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mindee S. Hite, Rochester General Hospital
- Investigators
- Mindee S Hite, Pharm.D., Principal investigator, Rochester General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02118688
- Sponsor's protocol ID
- ICUDelirium
- Status last verified
- Sep 2019
- First submitted
- 9 Apr 2014
- Last updated
- 10 Sep 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Risperidone and Trazodone Monotherapy and Combination Therapy in Critically Ill Patients With Delirium: A Four-arm Prospective, Randomized, Double-blind, Placebo-controlled Pilot Study
- ClinicalTrials.gov ID
- NCT02118688
- Acronym / sponsor ID
- ICUDelirium
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of enrollment
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Rochester General HospitalUniversity, hospital or other
- Study start
- Mar 2011
- Primary completion
- Mar 2016 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 21 Apr 2014 (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.
The purpose of this randomized clinical trial is to determine whether risperidone alone, trazodone alone, or a combination of risperidone and trazodone is superior for the treatment of ICU acquired delirium. The hypothesis is that combination therapy is superior to either agent alone in treating ICU acquired delirium and sustaining delirium free time.
Detailed description
Delirium is defined as a disturbance of consciousness characterized by an acute onset of impaired cognitive function. Although delirium is thought to be common in the Intensive Care Unit (ICU) there are few studies that have evaluated its incidences, risks and outcomes. It has been associated with increased morbidity, and mortality and increased cost to the healthcare system. In addition to the uncertainty of the incidence of ICU delirium, there is a lack of information about the effects that certain pharmacological treatments have on delirious patients.
The rationale for this study is to evaluate the efficacy and safety of risperidone alone, trazodone alone, and risperidone plus trazodone for the treatment of delirium in critically ill patients when compared to placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboDrug: Placebo * Placebo suspension administered PO/NG/FT q12h to mimic risperidone * Placebo suspension administered PO/NG/FT q8h to mimic trazodone |
| Risperidone alone | Active comparator | Drug: Risperidone, Drug: PlaceboDrug: Risperidone * Initiate risperidone at 1 mg PO/NG/FT q12h * Risperidone dose can be titrated upwards every 24 hours by increments of 0.5 mg per dose * Maximum risperidone daily dose of 6 mg per day (3 mg every 12 hours) |
| Trazodone alone | Active comparator | Drug: Trazodone, Drug: PlaceboDrug: Trazodone * Initiate trazodone dosing at 50 mg PO/NG/FT q8h * Trazodone dose can be titrated upwards every 24 hours by 25 mg per dose * Maximum trazodone daily dose 600 mg per day (200 mg every 8 hours) |
| Risperidone and Trazodone combination | Active comparator | Drug: Risperidone, Drug: TrazodoneDrug: Risperidone * Initiate risperidone at 1 mg PO/NG/FT q12h * Risperidone dose can be titrated upwards every 24 hours by increments of 0.5 mg per dose * Maximum risperidone daily dose of 6 mg per day (3 mg every 12 hours) Drug: Trazodone * Initiate risperidone at 1 mg PO/NG/FT q12h * Risperidone dose can be titrated upwards every 24 hours by increments of 0.5 mg per dose * Maximum risperidone daily dose of 6 mg per day (3 mg every 12 hours) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age greater than 18 years old who are admitted for more than 24 hours in the MICU or SICU
- Patients diagnosed with delirium by primary team (screened positive for delirium using the CAM-ICU or with clinical manifestations of delirium)
- Patients have an order for as-needed haloperidol or have received a one-time dose of haloperidol within 24 hours of randomization
- Patients must be tolerating enteral feeding (greater than 20 mL/hour for more than 12 hours)
Key exclusion criteria (13 listed)
- Patients who are unlikely to survive 24 hours after admission to the ICU
- Patients who are admitted with a primary neurological condition or injury (i.e. stroke, active seizures, prolonged coma, overdose)
- Patients who can not actively participate in delirium assessment
- Patients actively withdrawing from alcohol or narcotics
- Patients who were treated with any antipsychotic or trazodone within 30 days prior to ICU admission
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 |
|---|---|---|
| Risperidone | Drug | Risperidone alone, Risperidone and Trazodone combination |
| Trazodone | Drug | Risperidone and Trazodone combination, Trazodone alone |
| Placebo | Drug | Placebo, Risperidone alone, Trazodone alone |
Primary outcome
The number of days patients are without delirium during the study period (delirium-free days)
Time frame: Every 24 hours (up to 14 days)
The number of days patients are without delirium during the study period (delirium-free days)
12 secondary outcomes
Daily prevalence of delirium as indicated by a positive Confusion Assessment Method in the ICU (CAM-ICU)
Time frame: Every 24 hours (up to 14 days)
Resolution of delirium as indicated by a negative Confusion Assessment Method in the ICU (CAM-ICU) for more than 24 hours
Time frame: Every 24 hours (up to 14 days)
The number of patients who require rescue medications, the type of rescue medications utilized, and the amount of rescue medications per day
Time frame: Every 24 hours (up to 14 days)
The number of patients who receive sedative agents, amount of midazolam equivalents per day, and the number of days in which patients receive a sedative agent
Time frame: Every 24 hours (up to 14 days)
The number of patients who receive pain medications, amount of fentanyl equivalents per day, and the number of days in which patients receive a pain medication
Time frame: Every 24 hours (up to 24 hours)
The number of hours spent agitated (RASS score between +4 and +2) as a percent of the time that the study drug was administered
Time frame: Every 24 hours (up to 14 days)
The number of hours spent excessively sedated or in a coma state (RASS score between -4 to -5) as a percent of the time that the study drug was administered
Time frame: Every 24 hours (up to 14 days)
The duration of mechanical ventilation from initial intubation to extubation as long as the patient remained extubated for more than 48 hours.
Time frame: Time (hours) from initial intubation to extubation (as long as patient not reintubated within 48 hours)
The number of days that the patients were alive and breathing without assistance during the study period (ventilator-free days)
Time frame: Time (days) from extubation to patient discharge (as long as patient not reintubated within 48 hours)
The number of episodes and number of patients who experience clinically significant QTc prolongation (≥ 500 msec or an increase of more than 60 msec from baseline)
Time frame: QTc interval evaluated q12h during period of study drug administration (up to 14 days)
The number of episodes and number of patients who experience clinically significant extrapyramidal effects (as evidenced by a positive Simpson-Angus Scale Score)
Time frame: Extrapyramidal effects evaluated by bedside nurse q12h during period of study drug administration (up to 14 days). Investigator will confirm RN suspicion of extrapyramidal effects using Simpson-Angus Score.
All-cause mortality and 28-day mortality
Time frame: At 14 and 28 days
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 10 Sep 2019.
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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.
Mindee S Hite, Pharm.D. principal investigator
Rochester General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Risperidone and Trazodone in people with Delirium and Agitation, run by Rochester General Hospital at 1 site in United States.
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 4 inclusion and 13 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 10 Sep 2019. 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 States. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
The number of days patients are without delirium during the study period (delirium-free days) (time frame: Every 24 hours (up to 14 days)). 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 10 Sep 2019.