Optimizing Early Nutrition Support in Severe Stroke-2

NCT05998902 | Recruiting Phase 3 DMC

• 1 other identifier: XJLL-KY-20222214
• Study Type: interventional
• Target: 546
• Locations: 1 country
• Sites: 30

Brief Summary

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.

Conditions

Severe Stroke; Acute Stroke; Dysphagia

Keywords

Severe Stroke; Acute Stroke; Dysphagia; supplemental parenteral nutrition; trophic feeding; pneumonia

Outcome Measures

Primary Outcomes (1)

• Incidence of post stroke pneumonia

  up to 7 days

Secondary Outcomes (20)

• 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 utilization

  up to 7 days

• The incidence of gastrointestinal complications

  up to 7 days

Other Outcomes (3)

• Composite endpoint of all-cause mortality and post-stroke pneumonia

  90 days after randomization

• Composite endpoint of all-cause mortality and post-stroke pneumonia

  7 days after randomization

• Time from randomization to the first occurrence of either all-cause death or post-stroke pneumonia

  90 days after randomization

Study Arms (2)

Full enteral feeding

ACTIVE COMPARATOR

Patients will receive full enteral feeding through nasogastric tube or nasointestinal tube.

Procedure: Full enteral feeding

Trophic enteral feeding combined with supplemental parenteral nutrition

EXPERIMENTAL

Patients will receive trophic enteral feeding combined with supplemental parenteral feeding.

Procedure: Trophic enteral feeding combined with supplemental parenteral nutrition

Interventions

Trophic enteral feeding combined with supplemental parenteral nutrition PROCEDURE

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.

Trophic enteral feeding combined with supplemental parenteral nutrition

Full enteral feeding PROCEDURE

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.

Full enteral feeding

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Wen Jiang-3: lead
• Tang-Du Hospital: collaborator
• Xi'an Central Hospital: collaborator
• Xi'an Gaoxin Hospital: collaborator
• Xi'an No.3 Hospital: collaborator
• First People's Hospital of Xianyang: collaborator
• Nanfang Hospital, Southern Medical University: collaborator
• Tongji Hospital: collaborator
• Qilu Hospital of Shandong University: collaborator
• The Second Hospital of Shandong University: collaborator
• PLA 960 Hospital: collaborator
• Daping Hospital, The Third Military Medical University (Army Medical University): collaborator
• The Second Affiliated Hospital of Guangzhou University of Chinese Medicine: collaborator
• First Hospital Affiliated to Zhengzhou University: collaborator
• Gansu Provincial Central Hospital: collaborator
• The First Hospital of Changsha City: collaborator
• Shaanxi Provincial People's Hospital: collaborator
• Yulin No.2 Hospital: collaborator
• Yulin No.1 Hospital: collaborator
• Xijing Hospital: collaborator
• First Affiliated Hospital Xi'an Jiaotong University: collaborator

Study Sites (30)

Chongqing University Three Gorges Hospital

Chongqing, Chongqing Municipality, 404100, China

RECRUITING

Daping Hospital, The Third Military Medical University

Chongqing, Chongqing Municipality, China

RECRUITING

Gansu Provincal Central Hospital

Lanzhou, Gansu, China

RECRUITING

Nanfang Hospital, Southern Medical University

Guangzhou, Guangdong, China

NOT YET RECRUITING

The Second Affiliated Hospital of Guangzhou University of Chinese Medicine

Guangzhou, Guangdong, China

RECRUITING

The Affiliated Hospital of Guizhou Medical University

Guiyang, Guizhou, 550000, China

RECRUITING

First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

RECRUITING

Tongji Hospital

Wuhan, Hubei, China

RECRUITING

The First Hospital of Changsha City

Changsha, Hunan, China

NOT YET RECRUITING

The Second Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330000, China

RECRUITING

General Hospital of Ningxia Medical University

Yinchuan, Ningxia, 750000, China

RECRUITING

Shaanxi Second Provincal People's Hospital

Xi'an, Shaanxi, 710000, China

RECRUITING

Tangdu Hospital

Xi'an, Shaanxi, 710000, China

NOT YET RECRUITING

The first affiliated hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, 710000, China

RECRUITING

Xi'an Central Hospital

Xi'an, Shaanxi, 710000, China

NOT YET RECRUITING

Department of Neurology, Xijing Hospital

Xi'an, Shaanxi, China

RECRUITING

Shannxi Provincal People's Hospital

Xi'an, Shaanxi, China

NOT YET RECRUITING

The First Affiliated Hospital of Xi'an Medical University

Xi'an, Shaanxi, China

RECRUITING

Xi'an Gaoxin Hospital

Xi'an, Shaanxi, China

RECRUITING

Xi'an No.3 Hospital

Xi'an, Shaanxi, China

RECRUITING

Xianyang Hospital, Yan'an University

Xianyang, Shaanxi, 712000, China

RECRUITING

The First People's Hospital of Xianyang

Xianyang, Shaanxi, China

RECRUITING

Yulin No.1 Hospital

Yulin, Shaanxi, China

NOT YET RECRUITING

Yulin No.2 Hospital

Yulin, Shaanxi, China

NOT YET RECRUITING

Qilu Hospital of Shangdong University

Jinan, Shandong, China

NOT YET RECRUITING

The PLA 960 Hospital

Jinan, Shandong, China

RECRUITING

The Second Hospital of Shandong University

Jinan, Shandong, China

RECRUITING

Liaocheng People's Hospital

Liaocheng, Shandong, 252000, China

RECRUITING

People's Hospital of Xinjiang Uygur Autonomous Region

Ürümqi, Xinjiang, 830000, China

RECRUITING

The Second Affiliated Hospital of Xinjiang Medical University

Ürümqi, Xinjiang, 830000, China

RECRUITING

Related Publications (22)

• Meisel A, Smith CJ. Prevention of stroke-associated pneumonia: where next? Lancet. 2015 Nov 7;386(10006):1802-4. doi: 10.1016/S0140-6736(15)00127-0. Epub 2015 Sep 3. No abstract available.

  PMID: 26343837 BACKGROUND

• Wilson RD. Mortality and cost of pneumonia after stroke for different risk groups. J Stroke Cerebrovasc Dis. 2012 Jan;21(1):61-7. doi: 10.1016/j.jstrokecerebrovasdis.2010.05.002. Epub 2010 Jun 17.

  PMID: 22225864 BACKGROUND

• Kishore AK, Vail A, Chamorro A, Garau J, Hopkins SJ, Di Napoli M, Kalra L, Langhorne P, Montaner J, Roffe C, Rudd AG, Tyrrell PJ, van de Beek D, Woodhead M, Meisel A, Smith CJ. How is pneumonia diagnosed in clinical stroke research? A systematic review and meta-analysis. Stroke. 2015 May;46(5):1202-9. doi: 10.1161/STROKEAHA.114.007843. Epub 2015 Apr 9.

  PMID: 25858238 BACKGROUND

• Suda S, Aoki J, Shimoyama T, Suzuki K, Sakamoto Y, Katano T, Okubo S, Nito C, Nishiyama Y, Mishina M, Kimura K. Stroke-associated infection independently predicts 3-month poor functional outcome and mortality. J Neurol. 2018 Feb;265(2):370-375. doi: 10.1007/s00415-017-8714-6. Epub 2017 Dec 16.

  PMID: 29249057 BACKGROUND

• Cohen DL, Roffe C, Beavan J, Blackett B, Fairfield CA, Hamdy S, Havard D, McFarlane M, McLauglin C, Randall M, Robson K, Scutt P, Smith C, Smithard D, Sprigg N, Warusevitane A, Watkins C, Woodhouse L, Bath PM. Post-stroke dysphagia: A review and design considerations for future trials. Int J Stroke. 2016 Jun;11(4):399-411. doi: 10.1177/1747493016639057. Epub 2016 Mar 22.

  PMID: 27006423 BACKGROUND

• Westendorp WF, Nederkoorn PJ, Vermeij JD, Dijkgraaf MG, van de Beek D. Post-stroke infection: a systematic review and meta-analysis. BMC Neurol. 2011 Sep 20;11:110. doi: 10.1186/1471-2377-11-110.

  PMID: 21933425 BACKGROUND

• Finlayson O, Kapral M, Hall R, Asllani E, Selchen D, Saposnik G; Canadian Stroke Network; Stroke Outcome Research Canada (SORCan) Working Group. Risk factors, inpatient care, and outcomes of pneumonia after ischemic stroke. Neurology. 2011 Oct 4;77(14):1338-45. doi: 10.1212/WNL.0b013e31823152b1. Epub 2011 Sep 21.

  PMID: 21940613 BACKGROUND

• de Montmollin E, Ruckly S, Schwebel C, Philippart F, Adrie C, Mariotte E, Marcotte G, Cohen Y, Sztrymf B, da Silva D, Bruneel F, Gainnier M, Garrouste-Orgeas M, Sonneville R, Timsit JF; OUTCOMEREA Study Group. Pneumonia in acute ischemic stroke patients requiring invasive ventilation: Impact on short and long-term outcomes. J Infect. 2019 Sep;79(3):220-227. doi: 10.1016/j.jinf.2019.06.012. Epub 2019 Jun 22.

  PMID: 31238051 BACKGROUND

• Suntrup-Krueger S, Kemmling A, Warnecke T, Hamacher C, Oelenberg S, Niederstadt T, Heindel W, Wiendl H, Dziewas R. The impact of lesion location on dysphagia incidence, pattern and complications in acute stroke. Part 2: Oropharyngeal residue, swallow and cough response, and pneumonia. Eur J Neurol. 2017 Jun;24(6):867-874. doi: 10.1111/ene.13307. Epub 2017 Apr 27.

  PMID: 28449405 BACKGROUND

• Al-Khaled M. The multifactorial etiology of stroke-associated pneumonia. J Neurol Sci. 2019 May 15;400:30-31. doi: 10.1016/j.jns.2019.02.042. Epub 2019 Mar 12. No abstract available.

  PMID: 30884370 BACKGROUND

• McClave SA, DeMeo MT, DeLegge MH, DiSario JA, Heyland DK, Maloney JP, Metheny NA, Moore FA, Scolapio JS, Spain DA, Zaloga GP. North American Summit on Aspiration in the Critically Ill Patient: consensus statement. JPEN J Parenter Enteral Nutr. 2002 Nov-Dec;26(6 Suppl):S80-5. doi: 10.1177/014860710202600613.

  PMID: 12405628 BACKGROUND

• Jabbar A, Chang WK, Dryden GW, McClave SA. Gut immunology and the differential response to feeding and starvation. Nutr Clin Pract. 2003 Dec;18(6):461-82. doi: 10.1177/0115426503018006461.

  PMID: 16215082 BACKGROUND

• Singer P, Blaser AR, Berger MM, Alhazzani W, Calder PC, Casaer MP, Hiesmayr M, Mayer K, Montejo JC, Pichard C, Preiser JC, van Zanten ARH, Oczkowski S, Szczeklik W, Bischoff SC. ESPEN guideline on clinical nutrition in the intensive care unit. Clin Nutr. 2019 Feb;38(1):48-79. doi: 10.1016/j.clnu.2018.08.037. Epub 2018 Sep 29.

  PMID: 30348463 BACKGROUND

• Uozumi M, Sanui M, Komuro T, Iizuka Y, Kamio T, Koyama H, Mouri H, Masuyama T, Ono K, Lefor AK. Interruption of enteral nutrition in the intensive care unit: a single-center survey. J Intensive Care. 2017 Aug 4;5:52. doi: 10.1186/s40560-017-0245-9. eCollection 2017.

  PMID: 28794882 BACKGROUND

• Harvey SE, Parrott F, Harrison DA, Bear DE, Segaran E, Beale R, Bellingan G, Leonard R, Mythen MG, Rowan KM; CALORIES Trial Investigators. Trial of the route of early nutritional support in critically ill adults. N Engl J Med. 2014 Oct 30;371(18):1673-84. doi: 10.1056/NEJMoa1409860. Epub 2014 Oct 1.

  PMID: 25271389 BACKGROUND

• Altintas ND, Aydin K, Turkoglu MA, Abbasoglu O, Topeli A. Effect of enteral versus parenteral nutrition on outcome of medical patients requiring mechanical ventilation. Nutr Clin Pract. 2011 Jun;26(3):322-9. doi: 10.1177/0884533611405790. Epub 2011 Apr 29.

  PMID: 21531737 BACKGROUND

• Reignier J, Boisrame-Helms J, Brisard L, Lascarrou JB, Ait Hssain A, Anguel N, Argaud L, Asehnoune K, Asfar P, Bellec F, Botoc V, Bretagnol A, Bui HN, Canet E, Da Silva D, Darmon M, Das V, Devaquet J, Djibre M, Ganster F, Garrouste-Orgeas M, Gaudry S, Gontier O, Guerin C, Guidet B, Guitton C, Herbrecht JE, Lacherade JC, Letocart P, Martino F, Maxime V, Mercier E, Mira JP, Nseir S, Piton G, Quenot JP, Richecoeur J, Rigaud JP, Robert R, Rolin N, Schwebel C, Sirodot M, Tinturier F, Thevenin D, Giraudeau B, Le Gouge A; NUTRIREA-2 Trial Investigators; Clinical Research in Intensive Care and Sepsis (CRICS) group. Enteral versus parenteral early nutrition in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group study (NUTRIREA-2). Lancet. 2018 Jan 13;391(10116):133-143. doi: 10.1016/S0140-6736(17)32146-3. Epub 2017 Nov 8.

  PMID: 29128300 BACKGROUND

• Compher C, Bingham AL, McCall M, Patel J, Rice TW, Braunschweig C, McKeever L. Guidelines for the provision of nutrition support therapy in the adult critically ill patient: The American Society for Parenteral and Enteral Nutrition. JPEN J Parenter Enteral Nutr. 2022 Jan;46(1):12-41. doi: 10.1002/jpen.2267. Epub 2022 Jan 3.

  PMID: 34784064 BACKGROUND

• Heidegger CP, Berger MM, Graf S, Zingg W, Darmon P, Costanza MC, Thibault R, Pichard C. Optimisation of energy provision with supplemental parenteral nutrition in critically ill patients: a randomised controlled clinical trial. Lancet. 2013 Feb 2;381(9864):385-93. doi: 10.1016/S0140-6736(12)61351-8. Epub 2012 Dec 3.

  PMID: 23218813 BACKGROUND

• Shi J, Wei L, Huang R, Liao L. Effect of combined parenteral and enteral nutrition versus enteral nutrition alone for critically ill patients: A systematic review and meta-analysis. Medicine (Baltimore). 2018 Oct;97(41):e11874. doi: 10.1097/MD.0000000000011874.

  PMID: 30313021 BACKGROUND

• National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network; Rice TW, Wheeler AP, Thompson BT, Steingrub J, Hite RD, Moss M, Morris A, Dong N, Rock P. Initial trophic vs full enteral feeding in patients with acute lung injury: the EDEN randomized trial. JAMA. 2012 Feb 22;307(8):795-803. doi: 10.1001/jama.2012.137. Epub 2012 Feb 5.

  PMID: 22307571 BACKGROUND

• Zhao J, Yuan F, Song C, Yin R, Chang M, Zhang W, Zhang B, Yu L, Jia Y, Ma Y, Song Y, Wang C, Song C, Wang X, Shang L, Yang F, Jiang W; OPENS Trial Investigators. Safety and efficacy of three enteral feeding strategies in patients with severe stroke in China (OPENS): a multicentre, prospective, randomised, open-label, blinded-endpoint trial. Lancet Neurol. 2022 Apr;21(4):319-328. doi: 10.1016/S1474-4422(22)00010-2. Epub 2022 Feb 24.

  PMID: 35219379 BACKGROUND

MeSH Terms

Conditions

Stroke; Deglutition Disorders; Pneumonia

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Pharyngeal Diseases; Otorhinolaryngologic Diseases; Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Wen Jiang, Ph.D

CONTACT

86-029-84771319; jiangwen@fmmu.edu.cn

Xuan Wang, MD

CONTACT

86-029-84773664; 786369892@qq.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head of Neurology

Study Record Dates

• First Submitted: July 26, 2023
• First Posted: August 21, 2023
• Study Start: December 20, 2023
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): October 31, 2026
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (30)