Optimizing Early Nutrition Support in Severe Stroke-2

Study Overview
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Brief Summary
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Post stroke pneumonia (PSP) is one of the common early complications of stroke. Post-stroke infections, in general, are associated with less favorable neurologic outcomes. Aspiration is one of the most feared complications of enteral nutrition and can lead to the occurrence of pneumonia. Severe stroke patients are at high risk for aspiration due to some factors such as the reduced level of consciousness, inability to protect the airway and so on. The purpose of this study is to explore the ideal nutrition support strategy for patient with acute severe stroke to help reduce the incidence of PSP and improve the prognosis.

Detailed Description
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As one of the most common complication of stroke, some studies showed that post-stroke pneumonia (PSP) in stroke patients requiring intensive care is associated with an increase of ICU length of stay and hospital mortality and poorer functional outcomes in survivors. The peak period of PSP is within the first week after stroke. Aspiration and poor nutritional status are important factors leading to pneumonia in stroke patients. Compared with full enteral nutrition (EN), initial trophic enteral feeding was associated with less gastrointestinal intolerance and could reduce the rate of regurgitation. However, trophic enteral feeding could not meet the daily caloric needs and hypocaloric enteral nutrition might be associated with increased mortality. This study is designed to explore whether initial trophic enteral nutrition combined with supplemental parenteral nutrition (SPN) can help reduce the incidence of PSP and improve the prognosis in severe patients with stroke. This study will enroll 546 severe stroke patients who meet the inclusion criteria. Upon admission to the ICU, patients will be randomly assigned at a 1:1 ratio into groups of full enteral feeding (controlled) and trophic enteral feeding combined with supplemental parenteral feeding (experimented) for 7 days.

Official Title
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Trophic Enteral Feeding Combined With Supplemental Parenteral Nutrition Treatment in Patients With Severe Stroke (OPENS-2): a Multicentre, Prospective, Randomised, Open-label, Blinded-endpoint Trial

Conditions
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Acute Stroke, Severe Stroke, Dysphagia

Intervention / Treatment
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* Procedure: Trophic enteral feeding combined with supplemental parenteral nutrition
* Procedure: Full enteral feeding


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age≥18 years Definite diagnosis of acute stroke (GCS ≤12 or NIHSS≥11) The randomized nutritional treatment could be initiated up to 72 hours after symptom onset. Any cases of profiles #3 through 5 in Water Swallowing Test or with disorder of consciousness. Plan to receive nutritional support treatment for at least 7 days. Informed consent. Exclusion Criteria: Receiving parenteral nutrition support Contraindications of enteral nutrition Complicated with the disease which only have life expectancy < 7 days Admission with infection signs Dementia or severe disability (mRS>4) before stroke Antibiotics were used within the previous 7 days Subarachnoid hemorrhage, cerebral arteriovenous malformation Presence of coexisting medical conditions that could interfere with outcome assessment and/or follow-up (a. advanced cancer; b. severe pulmonary dysfunction [forced expiratory volume in 1 second < 50% or/and moderate to severe acute lung injury (PaO2/FiO2)<200mmHg]; c. cardiac insufficiency (NYHA class > I; cardiac structural and/or functional abnormalities such as EF< 50%, abnormal cardiac chamber enlargement, moderate/severe ventricular hypertrophy, or moderate/severe valvular stenosis); d. Severe liver failure [Child-Pugh score≥7]; e. Severe renal failure [glomerular filtration rate ≤30mL/min or serum creatinine ≥4mg/dL] Currently participating in other clinical trial Pregnant woman Patient who is considered highly likely not to adhere to the study treatment or follow-up protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Full enteral feeding<br>Patients will receive full enteral feeding through nasogastric tube or nasointestinal tube. | Procedure: Full enteral feeding<br>* The caloric goal of the first day is one-third of caloric requirements, the second day is half of caloric requirements, the third day is 70-100% and sustained for 1 week. Protein requirements are calculated at 1.2 to 1.5 g per kilogram of body weight per day. Enteral nutrition is given through nasogastric tube or nasointestinal tube.<br>|
| Experimental: Trophic enteral feeding combined with supplemental parenteral nutrition<br>Patients will receive trophic enteral feeding combined with supplemental parenteral feeding. | Procedure: Trophic enteral feeding combined with supplemental parenteral nutrition<br>* The caloric goal of the first day is one-third of caloric requirements, the second day is half of caloric requirements, the third day is 70-100% and sustained for 1 week. Patients will receive the trophic enteral feeding with a caloric target of 500kcal/d (20-35ml/h), and the remaining calories are supplemented by parenteral nutrition. Protein requirements are calculated at 1.2 to 1.5 g per kilogram of body weight per day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of post stroke pneumonia |  | up to 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The time from randomisation to the onset of the post stroke pneumonia |  | up to 7 days | 
| Daily calorie delivery |  | up to 7 days | 
| Daily protein delivery |  | up to 7 days | 
| Insulin dosage |  | up to 7 days | 
| The incidence of gastrointestinal complications | Vomiting, diarrhea, gastric retention, gastrointestinal bleeding | up to 7 days | 
| The use of prokinetic agents | The usage rate of prokinetic agents | up to 7 days | 
| The occurrence of infections | The rate and onset time of infections from randomisation to ICU discharge | 1 day of ICU discharge | 
| The length of ICU stay |  | 1 day of ICU discharge | 
| Mortality | from randomisation to all cause death during ICU stay. | 1 day of ICU discharge | 
| The All-cause mortality rate | from randomisation to all cause death at 28 days | 28 days after enrollment | 
| Cardiac failure | The incidence of cardiac failure from randomisation to ICU discharge | 1 day of ICU discharge | 
| Tracheotomy | The incidence of tracheotomy from randomisation to ICU discharge | 1 day of ICU discharge | 
| Mechanical ventilation | The incidence of mechanical ventilation from randomisation to ICU discharge | 1 day of ICU discharge | 
| Continuous renal replacement therapy | The incidence of continuous renal replacement therapy from randomisation to ICU discharge | 1 day of ICU discharge | 
| The use of vasoactive agents | The usage rate of vasoactive agents from randomisation to ICU discharge | 1 day of ICU discharge | 
| Deep venous thrombosis | The incidence of deep venous thrombosis from randomisation to ICU discharge | 1 day of ICU discharge | 
| The score of National Institute of Health stroke scale at ICU discharge | National Institute of Health stroke scale, with scores ranging from 0 (normal function) to 42 (functional impairment) was used to evaluate the impairment caused by a stroke. | 1 day of ICU discharge | 
| Glasgow Coma Scale at ICU discharge | Glasgow Coma Scale,with scores ranging from 3 (no response) to 15 (normal response), was used to grade the conscious state. | 1 day of ICU discharge | 
| modified Rankin scale at ICU discharge | modified Rankin scale score, with score ranging from 0 (normal) to 6 (death), was used to evaluate the functional outcomes after stroke. | 1 day of ICU discharge | 
| modified Rankin scale | modified Rankin scale score, with score ranging from 0 (normal) to 6 (death), was used to evaluate the functional outcomes after stroke. | 90 days after enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Severe Stroke, Acute Stroke, Dysphagia, supplemental parenteral nutrition, trophic feeding, pneumonia