ramelteon delirium prevention trial

JRCT ID: jRCTs031210673

Registered date:01/04/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Delirium
• Date of first enrollment: 01/04/2022
• Target sample size: 766
• Study type: Interventional

Intervention(s)

Ramelteon 8mg/tablet or Placebo 1 capsule per night orally or via nasogastric tube
Cointervention: multicomponent intervention to prevent delirium defined as below

Address cognitive impairment and/or disorientation
Address dehydration and/or constipation
Assess for hypoxia and optimise oxygen saturation
Address infection
Address immobility or limited mobility
Address pain
Carry out a medication review and optimization
Address poor nutrition
Address sensory impairment
Promote good sleep patterns and sleep hygiene

Outcome(s)

• Primary Outcome: Proportion of delirium diagnosis by psycho-oncologist with DSM-5 within 5 days after surgery among patients aged 75 years or older

Secondary Outcome

1. Proportion of delirium diagnosis by psycho-oncologist with DSM-5 within 5 days of surgery among patients aged 65 years or older
Outcomes below among patients aged 65 years or older or aged 75 years or older, respectively
2. Proportion of delirium diagnosis by psycho-oncologist with DSM-5 within 5 days of surgery except for delirium within 2 hours after surgery
3. Proportion of delirium assessed with Nu-DESC within 5 days of surgery
4. Severity of delirium assessed with Nu-DESC and DRS-R-98 within 5 days of surgery
5. Proportion of severe delirium diagnosis by psycho-oncologist with DSM-5 and DRS-R-98 within 5 days of surgery
6. Duration (days) of delirium by DSM-5
7. Direct cost of hospitalization after surgery to discharge
8. Duration (days) of hospitalization after surgery
9. Proportion of antipsychotics use within 5 days of surgery
10. Proportion of discontinuation of benzodiazepine receptor agonists at one day before surgery
11. Proportion of falls, self-removal of any tubes including drip infusion and self-extubation, and physical restraint within 5 days of surgery
12. Serum concentration of C-reactive protein at postoperative day1
13. Proportion of postoperative complications according to CD classification grade 2 or worse within 5 days of surgery
14. Proportion of postoperative complications according to CD classification grade 2 or worse within 90 days of surgery
15. Overall survival within 30 days of surgery
16. Overall survival within 90 days of surgery
17. Recurrence-free survival within 90 days of surgery
18. Patient's satisfaction and subjective symptoms at postoperative day5
19. Proportion of discharge to care facility insted of home
20. Stratified analisis by PSQI cutoff score of 6 at enrollment for proportion of delirium diagnosis by psycho-oncologist with DSM-5 within 5 days of surgery

Key inclusion & exclusion criteria

• Age minimum: >= 65age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) Pathologically confirmed and/or clinically suspected malignant tumor
2) Aged 65 or older at enrollment
3) Undergoing surgery under general anesthesia and postoperative hospitalization for 5 days or over
4) Preoperative ability to take medication orally or via nasogastric tube and postoperative plan to take medication orally or via nausal gastric tube from postoperative day 2 or earlier.
5) Written informed consent from patient or written informed consent from witness, who is not working in the present study, with patient's oral consent.

Exclude criteria

1) Diagnosed as delirium with DSM-5 at enrollment
2) Allergy to ramelteon
3) Sevea liver dysfunction according to criteria of total bil > 2.25 mg/dL, AST > 90 U/L, ALT > 126 U/L for male, or ALT > 69 U/L for female
4) History of participation to clinical trials within 4 weeks including a day of enrollment except for the completed protocol treatment and in the observation period
5) History of medication of ramelteon or flurvoxamine within 2 weeks including a day of enrollment
6) History of medication of suvorexant or lemborexant 2 weeks including a day of enrollment
7) History of epilepsy, Parkinson's dosease, or dementia with lewy bodies
8) Lactose intolerance
9) Planned surgical procesure including central nervous system or intracranial region.
10) History of drug or alcohol use disorder or daily alcohol intake over 60g or alcohol-related disease within 5 years including a day of enrollment
11) History of participation to the present study
12) Comorbidity of moderate to severe dementia according to MMSE-J < 21
13) Severe visual or auditory handicap, or illiteracy
14) ECOG PS 4 at enrolment
15) Judgement as inadequate by principal investigator or other investigators

Related Information

• Primary Sponsor: Matsuoka Hiromichi
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development