DeliriumPhase 4PRODEONCT03199950
PROfylactic Haloperidol in Patients Defined as High Risk for DElirium With Delirium Risk mOdel
A Phase 4 study testing Haloperidol in people with Delirium, run by Zuyderland Medisch Centrum at 1 site in Netherlands.
Trial summary
The hospital pharmacy at the Zuyderland Medical Centre developed the DElirium MOdel (DEMO) to predict which patients are at risk of developing a delirium in patients aged 60 or older. Read more about this study
- Who is it for?
- Ages 60 years and olderHealthy volunteers can take part
- Conditions the study is for
- Delirium
- What is being tested?
- Haloperidol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,366 participants
- Where
- 1 siteNetherlands
- Study dates
- 23 Jun 2017to 23 Nov 2018
- 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 60 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age >60 years
- Planned elective surgery
- General surgery or orthopaedic surgery
- At least one night postsurgical admission
- High-risk developing delirium according to the DEMO-model
- Absence of delirium pre-operatively
Who cannot join
- Less than 1-day postoperative admission in hospital
- Hypersensitivity to butyrophenone derivates
- Use of antipsychotics
- Not being able to take oral medication
- Presence of contraindications (lesions of basal ganglia, clinical significant heart disease (eg. recent acute myocardial infarction, non-compensated heart failure, arrythmias treated with drugs out of the NYHA(New York Heart Association)-class Ia and II anti-arrythmics), known prolongation of the QT interval, history of ventricular arrythmia and torsades de pointes, uncorrected hypokalemia.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
Zuyderland Medisch Centrum
Sittard, Limburg, 6162BG
Site sub-investigator, 088-4595947, prodeo@zuyderland.nl
Bauke Jansen, Bsc
About this study
Official title: Delirium: Is Prophylactic Drug Therapy Useful in High Risk Patients as Defined by the Delirium Risk Prediction Model?
The hospital pharmacy at the Zuyderland Medical Centre developed the DElirium MOdel (DEMO) to predict which patients are at risk of developing a delirium in patients aged 60 or older. With this delirium risk prediction model we aim to predict more accurately which patients are at high risk of developing a delirium and want to investigate if these patients can benefit from prophylactic haloperidol.
Read the detailed description
Intro: Delirium is a common postoperative complication within geriatric patients. It is described delirium as a very stressful experience for the patient which can lead to prolonged hospital stay, higher cost, additional morbidity and increased mortality.
In 2013 the hospital pharmacy at the Zuyderland Medical Center developed the delirium risk prediction model to determine the chance of development of a delirium in patients aged 60 or older. Electronically available data such as age, polypharmacy, use of anti-dementia drugs, anti-depressants, anti-parkinsonian drugs, anti-diabetics, analgesics and/or sleeping medication were used in the study. The delirium risk prediction model was validated prospectively after retrospective development. The model will be used in this study to predict the risk of developing delirium postoperatively.
We expect prophylactic haloperidol to be effective in patients with a high risk of developing a delirium according to the delirium risk prediction model.
Aim: The PRODEO-study aims to reduce the incidence of postoperative delirium by administering prophylactic haloperidol to patients with a high risk of developing delirium according to the delirium risk prediction model.
Methods: The study is a randomized and double blind single center study with two parallel groups. Subjects ≥60 years with increased risk of postoperative delirium according to the delirium risk prediction model undergoing elective chirurgical or elective orthopedic surgery are eligible. Subjects will be excluded if they already use anti-psychotic drugs, are not able to take oral medication or when there are contra-indications. Haloperidol (1mg) or placebo will be administered at set times postoperatively. Subjects receive haloperidol 2dd1mg or a placebo 2dd during a maximum of five days during admission. On day 3 blood samples will be obtained in order to determine the true concentration levels of haloperidol. The primary endpoint is delirium incidence within 5 days after surgery. Secondary endpoints are costs of treatment, number of admission days, adverse events, true concentration levels of haloperidol and duration and severity of delirium.
Results: The study will start in June 2017 with an inclusion rate of 20 patients per week. An incidence reduction of 30% in the intervention group is expected. To reach sufficient statistical power a study population of 1366 subjects is needed. Duration of the inclusion period is expected to be 18 months.
- Conditions
- Delirium
- Being tested
- Haloperidol, Placebo Oral Tablet
- Keywords
- Delirium, Haloperidol, Prophylactic, High-risk
- Medical subject headings
- Delirium
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HaloperidolDrug
Also called Haldol, RVG 55776
Haloperidol 2dd1mg (08.00am - 10.00pm)
Placebo Oral TabletDrug
Placebo oral 2dd (08.00am - 10.00pm)
| Study group | Role | What they receive |
|---|---|---|
| Prophylactic Haloperidol arm | Experimental | Patients will receive oral haloperidol 2dd1mg (08.00am \& 10.00pm) Receives: Drug: Haloperidol |
| No treatment | Placebo comparator | Patients will receive oral placebo 2dd (08.00am \& 10.00pm) Receives: Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurence of delirium
Will prophylactic haloperidol in high risk patients as established with DEMO reduce the incidence of delirium?
Measured: Delirium within 5 days postoperative
Secondary outcomes (6)
Costs of treatment
Total costs of hospital stay
Measured: up to 2 years
Days admitted to hospital
Total amount of days admitted to the hospital
Measured: an average of two weeks
Adverse events of intervention medication
Adverse events during admission in the hospital
Measured: an average of two weeks
Circulating concentration of Haloperidol
Blood sample collection at day, trough concentration haloperidol in blood sample
Measured: up to 2 years
Duration of delirium
Days DOS (Delirium observation scale) positive after surgery,
Measured: an average of two weeks
Severity of delirium
DOS scores during admission
Measured: an average of two weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2017
- Study start23 Jun 2017
- Primary completion23 Nov 2018 (estimated)
- Study completion23 Nov 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,366 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zuyderland Medisch Centrum
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hugo Van der Kuy, Zuyderland Medisch Centrum
- Investigators
- Hugo van der Kuy, Principal investigator, Zuyderland MC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03199950
- Sponsor's protocol ID
- 17-T-31
- Other IDs
- 2017-001260-37, 2017
- Acronym
- PRODEO
- Status last verified
- Jun 2017
- First submitted
- 23 Jun 2017
- Last updated
- 27 Jun 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Inouye SK, Studenski S, Tinetti ME, Kuchel GA. Geriatric syndromes: clinical, research, and policy implications of a core geriatric concept. J Am Geriatr Soc. 2007 May;55(5):780-91. doi: 10.1111/j.1532-5415.2007.01156.x.
PubMed 17493201Demeure MJ, Fain MJ. The elderly surgical patient and postoperative delirium. J Am Coll Surg. 2006 Nov;203(5):752-7. doi: 10.1016/j.jamcollsurg.2006.07.032. Epub 2006 Sep 26. No abstract available.
PubMed 17084339Salluh JI, Wang H, Schneider EB, Nagaraja N, Yenokyan G, Damluji A, Serafim RB, Stevens RD. Outcome of delirium in critically ill patients: systematic review and meta-analysis. BMJ. 2015 Jun 3;350:h2538. doi: 10.1136/bmj.h2538.
PubMed 26041151Leslie DL, Marcantonio ER, Zhang Y, Leo-Summers L, Inouye SK. One-year health care costs associated with delirium in the elderly population. Arch Intern Med. 2008 Jan 14;168(1):27-32. doi: 10.1001/archinternmed.2007.4.
PubMed 18195192Fukata S, Kawabata Y, Fujisiro K, Katagawa Y, Kuroiwa K, Akiyama H, Terabe Y, Ando M, Kawamura T, Hattori H. Haloperidol prophylaxis does not prevent postoperative delirium in elderly patients: a randomized, open-label prospective trial. Surg Today. 2014 Dec;44(12):2305-13. doi: 10.1007/s00595-014-0859-7. Epub 2014 Feb 16.
PubMed 24532143Wang W, Li HL, Wang DX, Zhu X, Li SL, Yao GQ, Chen KS, Gu XE, Zhu SN. Haloperidol prophylaxis decreases delirium incidence in elderly patients after noncardiac surgery: a randomized controlled trial*. Crit Care Med. 2012 Mar;40(3):731-9. doi: 10.1097/CCM.0b013e3182376e4f.
PubMed 22067628de Wit HA, Winkens B, Mestres Gonzalvo C, Hurkens KP, Mulder WJ, Janknegt R, Verhey FR, van der Kuy PH, Schols JM. The development of an automated ward independent delirium risk prediction model. Int J Clin Pharm. 2016 Aug;38(4):915-23. doi: 10.1007/s11096-016-0312-7. Epub 2016 May 13.
PubMed 27177868
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Delirium: Is Prophylactic Drug Therapy Useful in High Risk Patients as Defined by the Delirium Risk Prediction Model?
- ClinicalTrials.gov ID
- NCT03199950
- Acronym / sponsor ID
- PRODEO / 17-T-31
- Conditions
- Delirium
- Keywords
- Delirium, Haloperidol, Prophylactic, High-risk
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 1,366 participants (estimated)
- Lead sponsor
- Zuyderland Medisch CentrumUniversity, hospital or other
- Study start
- 23 Jun 2017 (actual)
- Primary completion
- 23 Nov 2018 (estimated)
- Study completion
- 23 Nov 2018 (estimated)
- First posted
- 27 Jun 2017 (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 hospital pharmacy at the Zuyderland Medical Centre developed the DElirium MOdel (DEMO) to predict which patients are at risk of developing a delirium in patients aged 60 or older. With this delirium risk prediction model we aim to predict more accurately which patients are at high risk of developing a delirium and want to investigate if these patients can benefit from prophylactic haloperidol.
Detailed description
Intro: Delirium is a common postoperative complication within geriatric patients. It is described delirium as a very stressful experience for the patient which can lead to prolonged hospital stay, higher cost, additional morbidity and increased mortality.
In 2013 the hospital pharmacy at the Zuyderland Medical Center developed the delirium risk prediction model to determine the chance of development of a delirium in patients aged 60 or older. Electronically available data such as age, polypharmacy, use of anti-dementia drugs, anti-depressants, anti-parkinsonian drugs, anti-diabetics, analgesics and/or sleeping medication were used in the study. The delirium risk prediction model was validated prospectively after retrospective development. The model will be used in this study to predict the risk of developing delirium postoperatively.
We expect prophylactic haloperidol to be effective in patients with a high risk of developing a delirium according to the delirium risk prediction model.
Aim: The PRODEO-study aims to reduce the incidence of postoperative delirium by administering prophylactic haloperidol to patients with a high risk of developing delirium according to the delirium risk prediction model.
Methods: The study is a randomized and double blind single center study with two parallel groups. Subjects ≥60 years with increased risk of postoperative delirium according to the delirium risk prediction model undergoing elective chirurgical or elective orthopedic surgery are eligible. Subjects will be excluded if they already use anti-psychotic drugs, are not able to take oral medication or when there are contra-indications. Haloperidol (1mg) or placebo will be administered at set times postoperatively. Subjects receive haloperidol 2dd1mg or a placebo 2dd during a maximum of five days during admission. On day 3 blood samples will be obtained in order to determine the true concentration levels of haloperidol. The primary endpoint is delirium incidence within 5 days after surgery. Secondary endpoints are costs of treatment, number of admission days, adverse events, true concentration levels of haloperidol and duration and severity of delirium.
Results: The study will start in June 2017 with an inclusion rate of 20 patients per week. An incidence reduction of 30% in the intervention group is expected. To reach sufficient statistical power a study population of 1366 subjects is needed. Duration of the inclusion period is expected to be 18 months.
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 |
|---|---|---|
| Prophylactic Haloperidol arm | Experimental | Drug: HaloperidolPatients will receive oral haloperidol 2dd1mg (08.00am \& 10.00pm) |
| No treatment | Placebo comparator | Drug: Placebo Oral TabletPatients will receive oral placebo 2dd (08.00am \& 10.00pm) |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age >60 years
- Planned elective surgery
- General surgery or orthopaedic surgery
- At least one night postsurgical admission
- High-risk developing delirium according to the DEMO-model
Key exclusion criteria (5 listed)
- Less than 1-day postoperative admission in hospital
- Hypersensitivity to butyrophenone derivates
- Use of antipsychotics
- Not being able to take oral medication
- Presence of contraindications (lesions of basal ganglia, clinical significant heart disease (eg. recent acute myocardial infarction, non-compensated heart failure, arrythmias treated with drugs out of the NYHA(New York Heart Association)-class Ia and II anti-arrythmics), known prolongation of the QT interval, history of ventricular arrythmia and torsades de pointes, uncorrected hypokalemia.
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 |
|---|---|---|
| HaloperidolAlso: Haldol, RVG 55776Haloperidol 2dd1mg (08.00am - 10.00pm) | Drug | Prophylactic Haloperidol arm |
| Placebo Oral TabletPlacebo oral 2dd (08.00am - 10.00pm) | Drug | No treatment |
Primary outcome
Occurence of delirium
Time frame: Delirium within 5 days postoperative
Will prophylactic haloperidol in high risk patients as established with DEMO reduce the incidence of delirium?
6 secondary outcomes
Costs of treatment
Time frame: up to 2 years
Days admitted to hospital
Time frame: an average of two weeks
Adverse events of intervention medication
Time frame: an average of two weeks
Circulating concentration of Haloperidol
Time frame: up to 2 years
Duration of delirium
Time frame: an average of two weeks
Severity of delirium
Time frame: an average of two weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2017.
- Background: PubMed 17493201Inouye SK, Studenski S, Tinetti ME, Kuchel GA. Geriatric syndromes: clinical, research, and policy implications of a core geriatric concept. J Am Geriatr Soc. 2007 May;55(5):780-91. doi: 10.1111/j.1532-5415.2007.01156.x.
- Background: PubMed 17084339Demeure MJ, Fain MJ. The elderly surgical patient and postoperative delirium. J Am Coll Surg. 2006 Nov;203(5):752-7. doi: 10.1016/j.jamcollsurg.2006.07.032. Epub 2006 Sep 26. No abstract available.
- Background: PubMed 26041151Salluh JI, Wang H, Schneider EB, Nagaraja N, Yenokyan G, Damluji A, Serafim RB, Stevens RD. Outcome of delirium in critically ill patients: systematic review and meta-analysis. BMJ. 2015 Jun 3;350:h2538. doi: 10.1136/bmj.h2538.
- Background: PubMed 18195192Leslie DL, Marcantonio ER, Zhang Y, Leo-Summers L, Inouye SK. One-year health care costs associated with delirium in the elderly population. Arch Intern Med. 2008 Jan 14;168(1):27-32. doi: 10.1001/archinternmed.2007.4.
- Background: PubMed 24532143Fukata S, Kawabata Y, Fujisiro K, Katagawa Y, Kuroiwa K, Akiyama H, Terabe Y, Ando M, Kawamura T, Hattori H. Haloperidol prophylaxis does not prevent postoperative delirium in elderly patients: a randomized, open-label prospective trial. Surg Today. 2014 Dec;44(12):2305-13. doi: 10.1007/s00595-014-0859-7. Epub 2014 Feb 16.
- Background: PubMed 22067628Wang W, Li HL, Wang DX, Zhu X, Li SL, Yao GQ, Chen KS, Gu XE, Zhu SN. Haloperidol prophylaxis decreases delirium incidence in elderly patients after noncardiac surgery: a randomized controlled trial*. Crit Care Med. 2012 Mar;40(3):731-9. doi: 10.1097/CCM.0b013e3182376e4f.
- Background: PubMed 27177868de Wit HA, Winkens B, Mestres Gonzalvo C, Hurkens KP, Mulder WJ, Janknegt R, Verhey FR, van der Kuy PH, Schols JM. The development of an automated ward independent delirium risk prediction model. Int J Clin Pharm. 2016 Aug;38(4):915-23. doi: 10.1007/s11096-016-0312-7. Epub 2016 May 13.
- Individual participant dataSharing planned: Undecided
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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.
Hugo van der Kuy principal investigator
Zuyderland MC
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 Haloperidol in people with Delirium, run by Zuyderland Medisch Centrum at 1 site in Netherlands.
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 6 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: status not confirmed, as of the sponsor's last update on 27 Jun 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 Netherlands. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Hugo van der Kuy (088 4595945 ext. 0031, h.vanderkuy@zuyderland.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurence of delirium (time frame: Delirium within 5 days postoperative). 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 NCT03199950, which also lists 7 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 27 Jun 2017.