Ramelteon for prevention of postoperative delirium in delirium high-risk cancer patients.: A randomized, double-blind, placebo-controlled multi-center trial, JORTC-PON02/J-SUPPORT2103/NCCH2103. (RAMP trial)
ramelteon delirium prevention trial (RAMP trial)
Matsuoka Hiromichi
National Cancer Center Japan
Tsukiji 5-1-1, Chuo-ku, Tokyo
+81-3-3542-2511
hiromima@ncc.go.jp
Sadahiro Ryoichi
National Cancer Center Japan
Tsukiji 5-1-1, Chuo-ku, Tokyo
+81-3-3542-2511
rsadahir@ncc.go.jp
Recruiting
April. 01, 2022
766
Interventional
randomized controlled trial
double blind
placebo control
parallel assignment
prevention purpose
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.
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
65age old over
No limit
Both
Delirium
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
Delirium, postoperative delirium, malignant tumor
ramelteon, multicomponent intervention
Delirium
ramelteon
Proportion of delirium diagnosis by psycho-oncologist with DSM-5 within 5 days after surgery among patients aged 75 years or older
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
Japan Agency for Medical Research and Development
Not applicable
National Cancer Center Hospital Certified Review Board
