Modified GuiGanLongMu Decoction for Preventing Delirium in Elderly Intensive Care Unit Patients: Study Protocol

Study Overview
=================
Brief Summary
-----------------
Elderly critically ill patients in the intensive care unit (ICU) are at risk of delirium, which is primarily characterized by acute consciousness impairment and perceptual, cognitive, and memory impairment, resulting in excess death, care expenditures, and acquired dementia, depression and anxiety, which severely affect the prognosis of critically ill patients. However, there are currently no effective pharmacological strategies for preventing delirium. Traditional Chinese Medicine (TCM) has extensive clinical experience in treating cognitive disorders. Therefore, we hypothesized that the use of GuiGanLongMu (GGLM) decoction, which is a classic prescription formula in traditional Chinese medicine, would reduce the incidence rate, shorten the duration and reduce the severity of delirium in ICU patients.

Detailed Description
-----------------
This revised GGLM decoction trial was designed to be a randomized, single-center, double-blind, placebo-controlled trial. A total of 208 elderly patients from two ICUs will be randomly allocated at a 1:1 ratio to the intervention group or the control group. Both groups will receive the ABCDEF (A2F) bundle strategy recommended by guidelines, a nonpharmacological multicomponent approach including pain and delirium management, breathing trial practice, analgesic and sedation usage control, family engagement and so on, to prevent delirium. The intervention group will additionally receive revised GGLM decoction twice a day for five days, followed by a 3-month follow-up. The control group will be received placebo made of flavoring agents. The primary endpoints are the incidence, severity, and duration of delirium. Secondary endpoints include the incidence of adverse events, the length of ICU stay, the duration of physical restraint, the duration of analgesic and sedative medication, the 28-day mortality rate, and the level of anxiety and depression in patients after discharge.

Official Title
-----------------
Modified GuiGanLongMu Decoction for Preventing Delirium in Elderly Intensive Care Unit Patients: Study Protocol for a Double Blind, Randomized, Placebo-controlled Trial

Conditions
-----------------
Delirium in Old Age

Intervention / Treatment
-----------------
* Drug: The modified GGLM decoction
* Behavioral: A2F bundle


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Critically ill patients aged between 60 and 90 years old Had an expected total ICU length of stay (LOS) of 72 hours or more Admitted to the ICU within 48 hours before screening Signed the informed consent form. Exclusion Criteria: Incapacitation preventing the assessment of delirium (i.e., coma, sedation, or active seizures) History of psychiatric disorders, dementia, Parkinson's disease, use of antipsychotic drugs, or alcohol dependence History of traumatic brain injury or brain infection Diagnosis of delirium prior to intervention initiation Allergies to medications used in the protocol or current participation in other drug studies Inability to communicate in Chinese or English Expected to be discharged or deceased within 72 hours of admission.

Ages Eligible for Study
-----------------
Minimum Age: 60 Years
Maximum Age: 90 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br>The modified GGLM decoction | Drug: The modified GGLM decoction<br>* GGLM decoction, originally documented in the classic Chinese medical book Shang Han Lun (Treatise on Febrile Diseases), is a notable herbal formula traditionally used to calm the mind and alleviate insomnia. The modified GGLM decoction is built upon the original four herbs (Gui Zhi [Ramulus Cinnamomi], Gan Cao [Glycyrrhizae Radix et Rhizoma], Long Gu [Os Draconis], Mu Li [Ostreae Concha]) and includes targeted Chinese herbs. As soothing the mind and nourishing yin to restrain yang is the core TCM treatment principle for delirium in ICU patients, we chose targeted herbs, including Ye Jiao Teng [Fallopia multiflora], He Huan Pi [silktree (Albizia) bark], Suan Zao Ren [Ziziphi Spinosae Semen], Shi Chang Pu [Acori Tatarinowii Rhizoma], Yuan Zhi [Polygalae Radix], and Jue Ming Zi [Cassiae Semen]. The modified GGLM decoction will all be purchased by Chongqing Traditional Chinese Medicine Hospital and prepared by the Pharmacy Department, with each dose amounting to 200 g.<br>* Other names: traditional Chinese medicine;Behavioral: A2F bundle<br>* A: assess, prevent, and manage pain; B: both spontaneous awakening and breathing trials; C: choice of analgesia and sedation; D: delirium assessment, prevention, and management; E: early mobility and exercise; and F: family engagement/empowerment<br>* Other names: ABCDEF bundle;|
| Placebo Comparator: Control group<br>the A2F bundle | Behavioral: A2F bundle<br>* A: assess, prevent, and manage pain; B: both spontaneous awakening and breathing trials; C: choice of analgesia and sedation; D: delirium assessment, prevention, and management; E: early mobility and exercise; and F: family engagement/empowerment<br>* Other names: ABCDEF bundle;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the prevalence of delirium | Assessment will be performed during the study period for all enrolled participants in a timely manner using the Confusion Assessment Method for the ICU (CAM-ICU). The CAM-ICU, a 2-minute assessment tool, has proven to be quick, valid, and reliable for the diagnosis of delirium in the ICU, making it beneficial for use in both clinical and research contexts. | Through study completion, an average of 1 year (November 31, 2023-November 31, 2024) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity of delirium | Throughout the study, the Confusion Assessment Method-Severity scale will be administered in each included patient. The total score of the Confusion Assessment Method-Severity scale can vary between 0 and 7, where 7 indicates the most severe condition. | Through study completion, an average of 1 year (November 31, 2023-November 31, 2024) | 
| Duration of delirium | Once delirium is diagnosed, the investigators will record its duration of the patient tests positive for the Confusion Assessment Method for the ICU (CAM-ICU) | Through study completion, an average of 1 year (November 31, 2023-November 31, 2024). |