Hypoactive DeliriumPhase 3THDOMNCT02345902
Treatment of Hypoactive Delirium and Outcome Measures
A Phase 3 study testing Haloperidol and non-pharmacologic measures in people with Hypoactive Delirium, run by Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran at 1 site in Mexico.
Trial summary
Haloperidol and Non-Pharmacologic Treatment are recognized treatments for delirium. This study will evaluate which is the best treatment for hypoactive delirium. Read more about this study
- Who is it for?
- Ages 70 years and older
- Conditions the study is for
- Hypoactive Delirium
- What is being tested?
- Haloperidol and non-pharmacologic measures
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteMexico
- Study dates
- Jan 2016to Dec 2018
- Phase
- Phase 3
- 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 70 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Patients who fulfill criteria for delirium according to CAM and DOSS
- Patients in hospitalization who are not receiving treatment for delirium
- Patients without treatment with antipsychotics for any other reason
- Patients whose legally proxy accepts to participate
Who cannot join
- Patients who have received pharmacologic treatment for delirium
- Patients with a corrected QT interval prolongation
- Patients who receive antipsychotics for any other reason
- Patients in another age group
- Patients whose legally proxy does not accept to participate
- Patients with dementia
Show all 13Show fewer
- Patients with Parkinson disease
- Patients with arrythmias
- Patients with language or hearing disorders that impede communication
- Patients hospitalized in the Intensive Care Unit
- Patients who are receiving benzodiazepines and anticholinergics
- Patients with dopamine agonists or antagonists
- Patients who develop a severe neurologic disease
Trial locations and contacts
1 site in 1 country.
Mexico1 site, 1 recruiting
- Recruiting
Department of Neurology and Psychiatry. Instituto Nacional de Ciencias Médicas y Nutrición
Mexico City, Mexico City, 14000
Maria Carmen Flores, MD, MSc, 54870900 ext. 2523, mcflormir@gmail.com
Sara Aguilar-Navarro, MD, MSc, 54870900 ext. 5701, sgan30@hotmail.com
About this study
Official title: Randomized Double-Blind Clinical Trial to Compare Haloperidol and Non-Pharmacologic Treatment Versus Non-Pharmacologic Treatment and Placebo, in Elderly Hospitalized Patients With Hypoactive Delirium
Haloperidol and Non-Pharmacologic Treatment are recognized treatments for delirium. This study will evaluate which is the best treatment for hypoactive delirium.
Read the detailed description
Background
Delirium is a cognitive disorder that affects attention and other mental functions. It has an acute onset (in hours or days), a fluctuating course and has various conditioning factors such as diseases or withdrawal or intoxication syndromes.
Delirium is a syndrome with multifactorial origin, it commonly presents in elderly patients, with a prevalence of 20%. Delirium develops when basal vulnerability interacts with precipitating factors.
Delirium has three types according to its psychomotor presentation, hyperactive (agitated), hypoactive (tranquil) or mixed. Delirium has serious outcomes, such as prolonged hospitalization (1), cognitive decline and dementia (2,3,4,), posttraumatic stress disorder (5) and a higher mortality (1).
A neurotransmitter imbalance between acetylcholine and dopamine explains delirium symptoms. A dopamine excess has various consequences: hallucinations that are present in 51 %, and delusions, present in up to 43% in hypoactive delirium. These symptoms produce acute stress in patients and caregivers. It is reported that 53.5% of patients recalled the episode of delirium and from these, 55% of them recalled it associated to hallucinations and 95% of them to delusions. Family recalled the event as stressful in 66%, nurses in 65% of those who did not have hallucinations and in 88% of those who had (6).
Hallucinations and delusions are risk factors for the development of posttraumatic stress disorder, which occurs in up 22% of patients.
Dopamine increase has been associated to apoptosis for its neurotoxic effects. Inflammation has a role in delirium. A study demonstrated that cortisol, Interleukin 6 ( IL-6) and protein S100 calcium binding protein B (S 100β) are all associated with delirium (7).
It is important to note that antipsychotics may have a neuro-protective effect by blocking dopamine receptors, and, therefore, diminishing the potential negative outcomes associated with dopamine excess. Furthermore in an observational study using haloperidol in the intensive care unit there was a decrease in mortality, possibly by its effects on inflammation, inhibiting the release of proinflammatory cytokines (8). One of the effects of haloperidol in vitro is the induction of interleukin receptor antagonist ( IL-IRA), which has shown to have an independent role in delirium. IL-IRA blocks the actions of Interleukin 1α (IL-1α) and interleukin 1β (IL-Iβ) . IL-IRA also downregulates ischaemic and excitotoxic damage (9).
Treatment of Delirium
Psychiatrist, Geriatricians and Neurologists, usually, treat delirium; however treatment strategies vary widely among disciplines, due to differences in the practice guidelines and local applications of current knowledge among centers. An integration of their treatment approaches could offer important clinical advantages. To refer some differences, The American Psychiatric Association (APA) Guidelines (10) recommend treatment with antipsychotics for elderly patients. Where haloperidol is the gold standard, with a dose of 0.25 to 0.50 mg every 4 hours, although the dose may need to be increased for those patients severely agitated. There is no mention among all subtypes of delirium. This guideline recognizes the non-pharmacologic intervention as part of the treatment.
On the other hand, Geriatrics Guidelines for the treatment of delirium, mention that the treatment of delirium should be mainly based on non-pharmacologic treatment. Restricting the pharmacologic treatment for those patients with severe manifestations of agitation (11). The NICE Guidelines mention that pharmacologic treatment in hypoactive delirium patients is indicated during one week to those patients with distress due to hallucinations (12).
Authors have mentioned that non-pharmacologic measures have not been assessed in clinical trials, and that pharmacologic treatment has not been recommended at this time (13). Furthermore, others addressed that currently, treatment with antipsychotics are used where non-pharmacologic measures have failed to treat psychotic symptoms. Or when the safety of patients or others are compromised, and that clinical trials with antipsychotics are few (14).
As it was mentioned before, there is no standardized treatment of delirium among different disciplines. Therefore, it is still on debate to determine which the best strategy in treating delirium is.
As far as we know, there are no clinical trials adequately evaluating haloperidol as the cornerstone of management in hypoactive delirium. Nonetheless, those patients who were exposed to a higher dose of haloperidol improved significantly with this antipsychotic (15).
Therefore, it is not known whether hypoactive delirium (the most frequent and difficult to recognize) should be treated with haloperidol at lower doses. Or if haloperidol should be used only in mixed and hyperactive types of delirium. Though despite few studies that have included patients with hypoactive delirium suggest that antipsychotics may have a role in the treatment of this delirium subtype (16).
Statement of the Problem
Hypoactive delirium is a common condition in hospitalized elderly patients. It is the most common type of delirium that carries more difficulty in its diagnosis. It is associated to a longer hospital stay, increased expenses associated to its diagnosis and more doubts on the most efficacious treatment strategy.
Surprisingly, even when hypoactive delirium is the most frequent, it is the hyperactive type the paradigm of study, and it is the one specifically mentioned in treatment guidelines.
To the best of our knowledge, there are no studies evaluating specifically haloperidol in hypoactive delirium. Some studies have excluded this type of delirium systematically or include all delirium subtypes where hypoactive delirium is poorly represented/analyzed.
Significance of the Investigation
There are few clinical studies correctly designed, exempt of methodological flaws and evaluating the most important clinical outcomes in delirium patients in general. There are no randomized clinical trials (RCTs) testing low-dose haloperidol against non-pharmacologic measures in the treatment of hypoactive delirium. Just few studies have included patients with hypoactive delirium with varying results, contributing to the lack of uniform recommendations (16). Currently, its treatment is based on the particular experiences of each clinical center without measuring its impact on relevant outcomes.
Furthermore, there are no studies evaluating perceived stress in patients and their caregivers, as well as posttraumatic stress in hypoactive delirium patients. None has evaluated cognitive decline after a hypoactive delirium treated either with antipsychotics or non-pharmacologic measures.
The purpose of the present RCT is to bring out knowledge about different treatments in elderly patients with hypoactive delirium.
- Conditions
- Hypoactive Delirium
- Being tested
- Haloperidol, Placebo, non-pharmacologic measures
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HaloperidolDrug
Also called haloperil
haloperidol 1.25 mg P.O q.d
PlaceboOther
placebo 1.25 mg P.O q.d
non-pharmacologic measuresOther
- Reorientation (i.e., calendar, clocks, familiar objects) B. Glasses and hearing devices for the particular patients needing such aids C. Avoidance of physical restraints D. Limitation of excessive personnel shifts or hospital room E. A tranquil and comfortable environment, especially at night, to avoid interruptions (i.e., dim light, low levels of noise) F. Adequate schedules for medication administration and to take vital signs or medical procedures G. Sleep hygiene (light in the room and movement during the day) H. Avoidance of dehydration I. Avoidance of medications use which are associated with delirium (e.g., psychoactive medications)
| Study group | Role | What they receive |
|---|---|---|
| Haloperidol and non-pharmacologic | Experimental | Haloperidol 1.25mg PO q. d. during nine days
Non-pharmacologic measures:
A. Reorientation (i.e., calendar, clocks, familiar objects) B. Glasses and hearing devices for the particular patients needing such aids C. Avoidance of physical restraints D. Limitation of excessive personnel shifts or hospital room E. A tranquil and comfortable environment, especially at night, to avoid interruptions (i.e., dim light, low levels of noise) F. Adequate schedules for medication administration and to take vital signs or medical procedures G. Sleep hygiene (light in the room and movement during the day) H. Avoidance of dehydration I. Avoidance of medications use which are associated with delirium (e.g., psychoactive medications) Receives: Drug: Haloperidol; Other: non-pharmacologic measures |
| Placebo and non-pharmacologic | Active comparator | Placebo 1.25 mg PO q.d during nine days.
Non-pharmacologic measures:
A. Reorientation (i.e., calendar, clocks, familiar objects) B. Glasses and hearing devices for the particular patients needing such aids C. Avoidance of physical restraints D. Limitation of excessive personnel shifts or hospital room E. A tranquil and comfortable environment, especially at night, to avoid interruptions (i.e., dim light, low levels of noise) F. Adequate schedules for medication administration and to take vital signs or medical procedures G. Sleep hygiene (light in the room and movement during the day) H. Avoidance of dehydration I. Avoidance of medications use which are associated with delirium (e.g., psychoactive medications) Receives: Other: Placebo; Other: non-pharmacologic measures |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in delirium severity
Reduction of 50% from the basal DOSS score
Measured: Participants will be followed at an expected average of nine days
Secondary outcomes (7)
Necessity of additional open label haloperidol doses to control delirium symptoms
In case the patient develops a hyperactive state will receive haloperidol in an open label dose, 1 mg that could be repeated every 4 hours in case the agitation persists, for a maximum daily dose of 6 mg. In this way, the dose will never exceed the recommended 10 mg dose per day.
If the patient persists with a hypoactive state (absence of improvement on the DOSS score), we will increase the dose to 2.5 mg or half a tablet (of haloperidol or placebo q.d.) or 3.75 mg,three quarters of a tablet ( of haloperidol or placebo q.d.)
Measured: Participants will be followed at an expected average of nine days
Delirium duration
Using the DOSS basal score and the CAM
Measured: Participants will be followed at an expected average of nine days
Perceived stress
in patients, health staff and caregivers of both groups using the delirium experience questionnaire
Measured: At 24 hours after delirium remission
Posttraumatic stress disorder
In patients of both groups using the posttraumatic stress disorder section of the Mini International Neuropsychiatry Interview
Measured: At 6 months after delirium remission
Cognitive impairment as assessed by Montreal Cognitive Assessment (MoCA) <24 points
Number of patients with <24 points in the Montreal Cognitive Assessment at 6 months after delirium remission, as compared with the number of patients with scoring >3.5 points in the Informant Questionnaire on Cognitive Decline in the Elderly, as an estimate of the baseline (pre-delirium) state
Measured: At 6 months after delirium remission
Cerebral blood flow as assessed by transcranial Doppler
in patients of both groups using a cerebral ultrasound
Measured: At baseline and after 24 h of delirium remission
Side effects associated with either intervention
We will list all adverse reactions associated with haloperidol (extra pyramidal effects, arrhythmias, hypersensitivity to the drug or corrected QT interval prolongation), the medication will be stopped in case of the appearance of an life-threatening reaction. We will consider this case when a patient needs ventilator support, use of cardiac amines, hemodialysis or the use of the Intensive Care Unit. These conditions will require opening the masking and exit the patient from the study.
Measured: Participants will be followed at an expected average of nine days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2015 (estimated)
- Study startJan 2016
- Primary completionMar 2018 (estimated)
- Study completionDec 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for Hypoactive 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Erwin Chiquete, MD, PhD, Study director, Instituto Nacional de Ciencias Médicas y NutriciónCarlos Cantú, MD, PhD, Study director, Instituto Nacional de Ciencias Médicas y Nutrición
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02345902
- Sponsor's protocol ID
- InstitutoNCMNSZ
- Acronym
- THDOM
- Status last verified
- Jan 2016
- First submitted
- 7 Nov 2014
- Last updated
- 21 Apr 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Khan BA, Zawahiri M, Campbell NL, Fox GC, Weinstein EJ, Nazir A, Farber MO, Buckley JD, Maclullich A, Boustani MA. Delirium in hospitalized patients: implications of current evidence on clinical practice and future avenues for research--a systematic evidence review. J Hosp Med. 2012 Sep;7(7):580-9. doi: 10.1002/jhm.1949. Epub 2012 Jun 8.
PubMed 22684893McCusker J, Cole M, Dendukuri N, Belzile E, Primeau F. Delirium in older medical inpatients and subsequent cognitive and functional status: a prospective study. CMAJ. 2001 Sep 4;165(5):575-83.
PubMed 11563209Davis DH, Muniz Terrera G, Keage H, Rahkonen T, Oinas M, Matthews FE, Cunningham C, Polvikoski T, Sulkava R, MacLullich AM, Brayne C. Delirium is a strong risk factor for dementia in the oldest-old: a population-based cohort study. Brain. 2012 Sep;135(Pt 9):2809-16. doi: 10.1093/brain/aws190. Epub 2012 Aug 9.
PubMed 22879644Saczynski JS, Marcantonio ER, Quach L, Fong TG, Gross A, Inouye SK, Jones RN. Cognitive trajectories after postoperative delirium. N Engl J Med. 2012 Jul 5;367(1):30-9. doi: 10.1056/NEJMoa1112923.
PubMed 22762316Griffiths RD, Jones C. Delirium, cognitive dysfunction and posttraumatic stress disorder. Curr Opin Anaesthesiol. 2007 Apr;20(2):124-9. doi: 10.1097/ACO.0b013e3280803d4b.
PubMed 17413395Breitbart W, Gibson C, Tremblay A. The delirium experience: delirium recall and delirium-related distress in hospitalized patients with cancer, their spouses/caregivers, and their nurses. Psychosomatics. 2002 May-Jun;43(3):183-94. doi: 10.1176/appi.psy.43.3.183.
PubMed 12075033van Munster BC, Bisschop PH, Zwinderman AH, Korevaar JC, Endert E, Wiersinga WJ, van Oosten HE, Goslings JC, de Rooij SE. Cortisol, interleukins and S100B in delirium in the elderly. Brain Cogn. 2010 Oct;74(1):18-23. doi: 10.1016/j.bandc.2010.05.010. Epub 2010 Jun 26.
PubMed 20580479Milbrandt EB, Kersten A, Kong L, Weissfeld LA, Clermont G, Fink MP, Angus DC. Haloperidol use is associated with lower hospital mortality in mechanically ventilated patients. Crit Care Med. 2005 Jan;33(1):226-9; discussion 263-5. doi: 10.1097/01.ccm.0000150743.16005.9a.
PubMed 15644675Adamis D, Lunn M, Martin FC, Treloar A, Gregson N, Hamilton G, Macdonald AJ. Cytokines and IGF-I in delirious and non-delirious acutely ill older medical inpatients. Age Ageing. 2009 May;38(3):326-32; discussion 251. doi: 10.1093/ageing/afp014. Epub 2009 Mar 5.
PubMed 19269948Practice guideline for the treatment of patients with delirium. American Psychiatric Association. Am J Psychiatry. 1999 May;156(5 Suppl):1-20. No abstract available.
PubMed 10327941Brajtman S, Wright D, Hogan DB, Allard P, Bruto V, Burne D, Gage L, Gagnon PR, Sadowski CA, Helsdingen S, Wilson K. Developing guidelines on the assessment and treatment of delirium in older adults at the end of life. Can Geriatr J. 2011 Jun;14(2):40-50. doi: 10.5770/cgj.v14i2.13. Epub 2011 Jul 7.
PubMed 23251311National Clinical Guideline Centre (UK). Delirium: Diagnosis, Prevention and Management [Internet]. London: Royal College of Physicians (UK); 2010 Jul. Available from http://www.ncbi.nlm.nih.gov/books/NBK65558/
PubMed 22319805Inouye SK, Westendorp RG, Saczynski JS, Kimchi EY, Cleinman AA. Delirium in elderly people--authors'reply. Lancet. 2014 Jun 14;383(9934):2045. doi: 10.1016/S0140-6736(14)60994-6. No abstract available.
PubMed 24931690Maclullich AM, Anand A, Davis DH, Jackson T, Barugh AJ, Hall RJ, Ferguson KJ, Meagher DJ, Cunningham C. New horizons in the pathogenesis, assessment and management of delirium. Age Ageing. 2013 Nov;42(6):667-74. doi: 10.1093/ageing/aft148. Epub 2013 Sep 25.
PubMed 24067500Boettger S, Friedlander M, Breitbart W, Passik S. Aripiprazole and haloperidol in the treatment of delirium. Aust N Z J Psychiatry. 2011 Jun;45(6):477-82. doi: 10.3109/00048674.2011.543411.
PubMed 21563866
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Double-Blind Clinical Trial to Compare Haloperidol and Non-Pharmacologic Treatment Versus Non-Pharmacologic Treatment and Placebo, in Elderly Hospitalized Patients With Hypoactive Delirium
- ClinicalTrials.gov ID
- NCT02345902
- Acronym / sponsor ID
- THDOM / InstitutoNCMNSZ
- Conditions
- Hypoactive Delirium
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Instituto Nacional de Ciencias Medicas y Nutricion Salvador ZubiranUniversity, hospital or other
- Study start
- Jan 2016
- Primary completion
- Mar 2018 (estimated)
- Study completion
- Dec 2018 (estimated)
- First posted
- 26 Jan 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Haloperidol and Non-Pharmacologic Treatment are recognized treatments for delirium. This study will evaluate which is the best treatment for hypoactive delirium.
Detailed description
Background
Delirium is a cognitive disorder that affects attention and other mental functions. It has an acute onset (in hours or days), a fluctuating course and has various conditioning factors such as diseases or withdrawal or intoxication syndromes.
Delirium is a syndrome with multifactorial origin, it commonly presents in elderly patients, with a prevalence of 20%. Delirium develops when basal vulnerability interacts with precipitating factors.
Delirium has three types according to its psychomotor presentation, hyperactive (agitated), hypoactive (tranquil) or mixed. Delirium has serious outcomes, such as prolonged hospitalization (1), cognitive decline and dementia (2,3,4,), posttraumatic stress disorder (5) and a higher mortality (1).
A neurotransmitter imbalance between acetylcholine and dopamine explains delirium symptoms. A dopamine excess has various consequences: hallucinations that are present in 51 %, and delusions, present in up to 43% in hypoactive delirium. These symptoms produce acute stress in patients and caregivers. It is reported that 53.5% of patients recalled the episode of delirium and from these, 55% of them recalled it associated to hallucinations and 95% of them to delusions. Family recalled the event as stressful in 66%, nurses in 65% of those who did not have hallucinations and in 88% of those who had (6).
Hallucinations and delusions are risk factors for the development of posttraumatic stress disorder, which occurs in up 22% of patients.
Dopamine increase has been associated to apoptosis for its neurotoxic effects. Inflammation has a role in delirium. A study demonstrated that cortisol, Interleukin 6 ( IL-6) and protein S100 calcium binding protein B (S 100β) are all associated with delirium (7).
It is important to note that antipsychotics may have a neuro-protective effect by blocking dopamine receptors, and, therefore, diminishing the potential negative outcomes associated with dopamine excess. Furthermore in an observational study using haloperidol in the intensive care unit there was a decrease in mortality, possibly by its effects on inflammation, inhibiting the release of proinflammatory cytokines (8). One of the effects of haloperidol in vitro is the induction of interleukin receptor antagonist ( IL-IRA), which has shown to have an independent role in delirium. IL-IRA blocks the actions of Interleukin 1α (IL-1α) and interleukin 1β (IL-Iβ) . IL-IRA also downregulates ischaemic and excitotoxic damage (9).
Treatment of Delirium
Psychiatrist, Geriatricians and Neurologists, usually, treat delirium; however treatment strategies vary widely among disciplines, due to differences in the practice guidelines and local applications of current knowledge among centers. An integration of their treatment approaches could offer important clinical advantages. To refer some differences, The American Psychiatric Association (APA) Guidelines (10) recommend treatment with antipsychotics for elderly patients. Where haloperidol is the gold standard, with a dose of 0.25 to 0.50 mg every 4 hours, although the dose may need to be increased for those patients severely agitated. There is no mention among all subtypes of delirium. This guideline recognizes the non-pharmacologic intervention as part of the treatment.
On the other hand, Geriatrics Guidelines for the treatment of delirium, mention that the treatment of delirium should be mainly based on non-pharmacologic treatment. Restricting the pharmacologic treatment for those patients with severe manifestations of agitation (11). The NICE Guidelines mention that pharmacologic treatment in hypoactive delirium patients is indicated during one week to those patients with distress due to hallucinations (12).
Authors have mentioned that non-pharmacologic measures have not been assessed in clinical trials, and that pharmacologic treatment has not been recommended at this time (13). Furthermore, others addressed that currently, treatment with antipsychotics are used where non-pharmacologic measures have failed to treat psychotic symptoms. Or when the safety of patients or others are compromised, and that clinical trials with antipsychotics are few (14).
As it was mentioned before, there is no standardized treatment of delirium among different disciplines. Therefore, it is still on debate to determine which the best strategy in treating delirium is.
As far as we know, there are no clinical trials adequately evaluating haloperidol as the cornerstone of management in hypoactive delirium. Nonetheless, those patients who were exposed to a higher dose of haloperidol improved significantly with this antipsychotic (15).
Therefore, it is not known whether hypoactive delirium (the most frequent and difficult to recognize) should be treated with haloperidol at lower doses. Or if haloperidol should be used only in mixed and hyperactive types of delirium. Though despite few studies that have included patients with hypoactive delirium suggest that antipsychotics may have a role in the treatment of this delirium subtype (16).
Statement of the Problem
Hypoactive delirium is a common condition in hospitalized elderly patients. It is the most common type of delirium that carries more difficulty in its diagnosis. It is associated to a longer hospital stay, increased expenses associated to its diagnosis and more doubts on the most efficacious treatment strategy.
Surprisingly, even when hypoactive delirium is the most frequent, it is the hyperactive type the paradigm of study, and it is the one specifically mentioned in treatment guidelines.
To the best of our knowledge, there are no studies evaluating specifically haloperidol in hypoactive delirium. Some studies have excluded this type of delirium systematically or include all delirium subtypes where hypoactive delirium is poorly represented/analyzed.
Significance of the Investigation
There are few clinical studies correctly designed, exempt of methodological flaws and evaluating the most important clinical outcomes in delirium patients in general. There are no randomized clinical trials (RCTs) testing low-dose haloperidol against non-pharmacologic measures in the treatment of hypoactive delirium. Just few studies have included patients with hypoactive delirium with varying results, contributing to the lack of uniform recommendations (16). Currently, its treatment is based on the particular experiences of each clinical center without measuring its impact on relevant outcomes.
Furthermore, there are no studies evaluating perceived stress in patients and their caregivers, as well as posttraumatic stress in hypoactive delirium patients. None has evaluated cognitive decline after a hypoactive delirium treated either with antipsychotics or non-pharmacologic measures.
The purpose of the present RCT is to bring out knowledge about different treatments in elderly patients with hypoactive delirium.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Haloperidol and non-pharmacologic | Experimental | Drug: Haloperidol, Other: non-pharmacologic measuresHaloperidol 1.25mg PO q. d. during nine days Non-pharmacologic measures: A. Reorientation (i.e., calendar, clocks, familiar objects) B. Glasses and hearing devices for the particular patients needing such aids C. Avoidance of physical restraints D. Limitation of excessive personnel shifts or hospital room E. A tranquil and comfortable environment, especially at night, to avoid interruptions (i.e., dim light, low levels of noise) F. Adequate schedules for medication administration and to take vital signs or medical procedures G. Sleep hygiene (light in the room and movement during the day) H. Avoidance of dehydration I. Avoidance of medications use which are associated with delirium (e.g., psychoactive medications) |
| Placebo and non-pharmacologic | Active comparator | Other: Placebo, Other: non-pharmacologic measuresPlacebo 1.25 mg PO q.d during nine days. Non-pharmacologic measures: A. Reorientation (i.e., calendar, clocks, familiar objects) B. Glasses and hearing devices for the particular patients needing such aids C. Avoidance of physical restraints D. Limitation of excessive personnel shifts or hospital room E. A tranquil and comfortable environment, especially at night, to avoid interruptions (i.e., dim light, low levels of noise) F. Adequate schedules for medication administration and to take vital signs or medical procedures G. Sleep hygiene (light in the room and movement during the day) H. Avoidance of dehydration I. Avoidance of medications use which are associated with delirium (e.g., psychoactive medications) |
Who may qualify
- Ages
- 70 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (4 listed)
- Patients who fulfill criteria for delirium according to CAM and DOSS
- Patients in hospitalization who are not receiving treatment for delirium
- Patients without treatment with antipsychotics for any other reason
- Patients whose legally proxy accepts to participate
Key exclusion criteria (13 listed)
- Patients who have received pharmacologic treatment for delirium
- Patients with a corrected QT interval prolongation
- Patients who receive antipsychotics for any other reason
- Patients in another age group
- Patients whose legally proxy does not accept to participate
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: haloperilhaloperidol 1.25 mg P.O q.d | Drug | Haloperidol and non-pharmacologic |
| Placeboplacebo 1.25 mg P.O q.d | Other | Placebo and non-pharmacologic |
| non-pharmacologic measuresA. Reorientation (i.e., calendar, clocks, familiar objects) B. Glasses and hearing devices for the particular patients needing such aids C. Avoidance of physical restraints D. Limitation of excessive personnel shifts or hospital room E. A tranquil and comfortable environment, especially at night, to avoid interruptions (i.e., dim light, low levels of noise) F. Adequate schedules for medication administration and to take vital signs or medical procedures G. Sleep hygiene (light in the room and movement during the day) H. Avoidance of dehydration I. Avoidance of medications use which are associated with delirium (e.g., psychoactive medications) | Other | Haloperidol and non-pharmacologic, Placebo and non-pharmacologic |
Primary outcome
Change in delirium severity
Time frame: Participants will be followed at an expected average of nine days
Reduction of 50% from the basal DOSS score
7 secondary outcomes
Necessity of additional open label haloperidol doses to control delirium symptoms
Time frame: Participants will be followed at an expected average of nine days
Delirium duration
Time frame: Participants will be followed at an expected average of nine days
Perceived stress
Time frame: At 24 hours after delirium remission
Posttraumatic stress disorder
Time frame: At 6 months after delirium remission
Cognitive impairment as assessed by Montreal Cognitive Assessment (MoCA) <24 points
Time frame: At 6 months after delirium remission
Cerebral blood flow as assessed by transcranial Doppler
Time frame: At baseline and after 24 h of delirium remission
Side effects associated with either intervention
Time frame: Participants will be followed at an expected average of nine days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2017.
- Background: PubMed 22684893Khan BA, Zawahiri M, Campbell NL, Fox GC, Weinstein EJ, Nazir A, Farber MO, Buckley JD, Maclullich A, Boustani MA. Delirium in hospitalized patients: implications of current evidence on clinical practice and future avenues for research--a systematic evidence review. J Hosp Med. 2012 Sep;7(7):580-9. doi: 10.1002/jhm.1949. Epub 2012 Jun 8.
- Background: PubMed 11563209McCusker J, Cole M, Dendukuri N, Belzile E, Primeau F. Delirium in older medical inpatients and subsequent cognitive and functional status: a prospective study. CMAJ. 2001 Sep 4;165(5):575-83.
- Background: PubMed 22879644Davis DH, Muniz Terrera G, Keage H, Rahkonen T, Oinas M, Matthews FE, Cunningham C, Polvikoski T, Sulkava R, MacLullich AM, Brayne C. Delirium is a strong risk factor for dementia in the oldest-old: a population-based cohort study. Brain. 2012 Sep;135(Pt 9):2809-16. doi: 10.1093/brain/aws190. Epub 2012 Aug 9.
- Background: PubMed 22762316Saczynski JS, Marcantonio ER, Quach L, Fong TG, Gross A, Inouye SK, Jones RN. Cognitive trajectories after postoperative delirium. N Engl J Med. 2012 Jul 5;367(1):30-9. doi: 10.1056/NEJMoa1112923.
- Background: PubMed 17413395Griffiths RD, Jones C. Delirium, cognitive dysfunction and posttraumatic stress disorder. Curr Opin Anaesthesiol. 2007 Apr;20(2):124-9. doi: 10.1097/ACO.0b013e3280803d4b.
- Background: PubMed 12075033Breitbart W, Gibson C, Tremblay A. The delirium experience: delirium recall and delirium-related distress in hospitalized patients with cancer, their spouses/caregivers, and their nurses. Psychosomatics. 2002 May-Jun;43(3):183-94. doi: 10.1176/appi.psy.43.3.183.
- Background: PubMed 20580479van Munster BC, Bisschop PH, Zwinderman AH, Korevaar JC, Endert E, Wiersinga WJ, van Oosten HE, Goslings JC, de Rooij SE. Cortisol, interleukins and S100B in delirium in the elderly. Brain Cogn. 2010 Oct;74(1):18-23. doi: 10.1016/j.bandc.2010.05.010. Epub 2010 Jun 26.
- Background: PubMed 15644675Milbrandt EB, Kersten A, Kong L, Weissfeld LA, Clermont G, Fink MP, Angus DC. Haloperidol use is associated with lower hospital mortality in mechanically ventilated patients. Crit Care Med. 2005 Jan;33(1):226-9; discussion 263-5. doi: 10.1097/01.ccm.0000150743.16005.9a.
- Background: PubMed 19269948Adamis D, Lunn M, Martin FC, Treloar A, Gregson N, Hamilton G, Macdonald AJ. Cytokines and IGF-I in delirious and non-delirious acutely ill older medical inpatients. Age Ageing. 2009 May;38(3):326-32; discussion 251. doi: 10.1093/ageing/afp014. Epub 2009 Mar 5.
- Background: PubMed 10327941Practice guideline for the treatment of patients with delirium. American Psychiatric Association. Am J Psychiatry. 1999 May;156(5 Suppl):1-20. No abstract available.
- Background: PubMed 23251311Brajtman S, Wright D, Hogan DB, Allard P, Bruto V, Burne D, Gage L, Gagnon PR, Sadowski CA, Helsdingen S, Wilson K. Developing guidelines on the assessment and treatment of delirium in older adults at the end of life. Can Geriatr J. 2011 Jun;14(2):40-50. doi: 10.5770/cgj.v14i2.13. Epub 2011 Jul 7.
- Background: PubMed 22319805National Clinical Guideline Centre (UK). Delirium: Diagnosis, Prevention and Management [Internet]. London: Royal College of Physicians (UK); 2010 Jul. Available from http://www.ncbi.nlm.nih.gov/books/NBK65558/
- 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.
Erwin Chiquete, MD, PhD study director
Instituto Nacional de Ciencias Médicas y Nutrición
Carlos Cantú, MD, PhD study director
Instituto Nacional de Ciencias Médicas y Nutrición
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Haloperidol and non-pharmacologic measures in people with Hypoactive Delirium, run by Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran at 1 site in Mexico.
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: status not confirmed, as of the sponsor's last update on 21 Apr 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 Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Maria Carmen Flores, MD, MSc (54870900 ext. 2523, mcflormir@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in delirium severity (time frame: Participants will be followed at an expected average of nine 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 NCT02345902, which also lists 16 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 21 Apr 2017.