Optimizing Early Nutrition Support in Severe Stroke-2

Dysphagia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05998902
• Other study ID #: XJLL-KY-20222214
• Status: Recruiting
• Phase: Phase 3
• Start date: December 20, 2023
• Est. completion date: October 31, 2026

Study information

• Verified date: March 2024
• Source: Xijing Hospital
• Contact: Wen Jiang, Ph.D
• Phone: 86-029-84771319
• Email: jiangwen[@]fmmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 546
• Est. completion date: October 31, 2026
• Est. primary completion date: July 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age=18 years

2. Definite diagnosis of acute stroke (GCS =12 or NIHSS=11)

3. The randomized nutritional treatment could be initiated up to 72 hours after symptom onset.

4. Any cases of profiles #3 through 5 in Water Swallowing Test or with disorder of consciousness.

5. Plan to receive nutritional support treatment for at least 7 days.

6. Informed consent.

Exclusion Criteria:

1. Receiving parenteral nutrition support

2. Contraindications of enteral nutrition

3. Complicated with the disease which only have life expectancy < 7 days

4. Admission with infection signs

5. Dementia or severe disability (mRS>4) before stroke

6. Antibiotics were used within the previous 7 days

7. Subarachnoid hemorrhage, cerebral arteriovenous malformation

8. 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]

9. Currently participating in other clinical trial

10. Pregnant woman

11. Patient who is considered highly likely not to adhere to the study treatment or follow-up protocol.

Related Conditions & MeSH terms

• Acute Stroke
• Deglutition Disorders
• Dysphagia
• Severe Stroke
• Stroke

Intervention

Procedure:
• Trophic enteral feeding combined with supplemental parenteral nutrition
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.
• Full enteral feeding
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.

Locations

Country	Name	City	State
China	The First Hospital of Changsha City	Changsha	Hunan
China	Daping Hospital, The Third Military Medical University	Chongqing	Chongqing
China	Nanfang Hospital, Southern Medical University	Guangzhou	Guangdong
China	The Second Affiliated Hospital of Guangzhou University of Chinese Medicine	Guangzhou	Guangdong
China	Qilu Hospital of Shangdong University	Jinan	Shandong
China	The PLA 960 Hospital	Jinan	Shandong
China	The Second Hospital of Shandong University	Jinan	Shandong
China	Gansu Provincal Central Hospital	Lanzhou	Gansu
China	Tongji Hospital	Wuhan	Hubei
China	Department of Neurology, Xijing Hospital	Xi'an	Shaanxi
China	Shannxi Provincal People's Hospital	Xi'an	Shaanxi
China	Tangdu Hospital	Xi'an	Shaanxi
China	The First Affiliated Hospital of Xi'an Medical University	Xi'an	Shaanxi
China	Xi'an Central Hospital	Xi'an	Shaanxi
China	Xi'an Gaoxin Hospital	Xi'an	Shaanxi
China	Xi'an No.3 Hospital	Xi'an	Shaanxi
China	The First People's Hospital of Xianyang	Xianyang	Shaanxi
China	Yulin No.1 Hospital	Yulin	Shaanxi
China	Yulin No.2 Hospital	Yulin	Shaanxi
China	First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan

Sponsors (21)

Lead Sponsor

Collaborator

Wen Jiang-3

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

Country where clinical trial is conducted

China, 

References & Publications (22)

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. — View Citation

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. — View Citation

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. — View Citation

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. Erratum In: JPEN J Parenter Enteral Nutr. 2022 Aug;46(6):1458-1459. — View Citation

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. — View Citation

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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. — View Citation

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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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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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. — View Citation

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. — View Citation

* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of post stroke pneumonia		up to 7 days
Secondary	The time from randomisation to the onset of the post stroke pneumonia		up to 7 days
Secondary	Daily calorie delivery		up to 7 days
Secondary	Daily protein delivery		up to 7 days
Secondary	Insulin dosage		up to 7 days
Secondary	The incidence of gastrointestinal complications	Vomiting, diarrhea, gastric retention, gastrointestinal bleeding	up to 7 days
Secondary	The use of prokinetic agents	The usage rate of prokinetic agents	up to 7 days
Secondary	The occurrence of infections	The rate and onset time of infections from randomisation to ICU discharge	1 day of ICU discharge
Secondary	The length of ICU stay		1 day of ICU discharge
Secondary	Mortality	from randomisation to all cause death during ICU stay.	1 day of ICU discharge
Secondary	The All-cause mortality rate	from randomisation to all cause death at 28 days	28 days after enrollment
Secondary	Cardiac failure	The incidence of cardiac failure from randomisation to ICU discharge	1 day of ICU discharge
Secondary	Tracheotomy	The incidence of tracheotomy from randomisation to ICU discharge	1 day of ICU discharge
Secondary	Mechanical ventilation	The incidence of mechanical ventilation from randomisation to ICU discharge	1 day of ICU discharge
Secondary	Continuous renal replacement therapy	The incidence of continuous renal replacement therapy from randomisation to ICU discharge	1 day of ICU discharge
Secondary	The use of vasoactive agents	The usage rate of vasoactive agents from randomisation to ICU discharge	1 day of ICU discharge
Secondary	Deep venous thrombosis	The incidence of deep venous thrombosis from randomisation to ICU discharge	1 day of ICU discharge
Secondary	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
Secondary	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
Secondary	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
Secondary	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