Nutrition and Exercise in Critical Illness (The NEXIS Trial): A Randomized Trial of Combined Cycle Ergometry and Amino Acids in the ICU
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 115
- 试验地点
- 7
- 主要终点
- Physical functioning
研究概览
简要总结
This study proposes a novel early intervention combining Intravenous (IV) amino acids plus in-bed cycle ergometry exercise to improve physical outcomes in critically ill patients. The investigators hypothesize that this innovative approach will improve short-term physical functioning outcomes (primary outcome), as well as amino acid metabolism, body composition, and patient-reported outcomes at 6-month follow-up.
详细描述
The evaluation of a combination of exercise and protein supplementation in intensive care unit (ICU) patients is novel and potentially very important. For instance, outside of the ICU, in other clinical conditions, the combination of protein supplementation and exercise improves protein synthesis, muscle mass, and muscle strength compared to protein or exercise alone.[63-70] Hence, an opportunity exists to improve ICU patients' physical outcomes via evaluating the combination of optimized protein intake and early exercise in the ICU setting.
The proposed intervention and hypothesis: The investigators propose a multi-centered Phase II RCT, with blinded outcomes assessment, of a combination of intravenous (IV) amino acid supplementation and early in-bed cycle ergometry exercise versus usual care in ICU patients requiring mechanical ventilation. The investigators hypothesize that this novel combined intervention will: (1) improve physical functioning at hospital discharge; (2) reduce muscle wasting with improved amino acid metabolism and protein synthesis in-hospital; and (3) improve health-related quality of life, physical functioning, and healthcare resource utilization at 6 months after enrollment. Preliminary data show feasibility and safety of IV amino acids and the proposed exercise intervention. The investigators have chosen a primary outcome that correlates well with long-term outcomes including mortality, hospitalization, and quality of life. [54] If this Phase II trial is positive, investigators will seek funding for a Phase III RCT to demonstrate sustained improvements with a longer-term patient-centered primary outcome and to examine the feasibility, and facilitators/barriers of delivery of this intervention by ICU nurses, physical therapists, and others. If proven effective, this combined intervention has potential to revolutionize care of ICU patients and have a major public health impact on the growing number of ICU survivors.
Objectives: To demonstrate that the innovative combination of amino acid supplementation plus early in-bed cycle ergometry exercise improves physical outcomes of ICU patients.
Specific Aims of Full Phase II RCT:
- Short-term performance-based physical function outcomes. To determine if a combined IV amino acid supplementation and in-bed cycle ergometry exercise intervention, compared to usual care, improves in hospital muscle strength and performance-based physical functioning outcomes in critically ill patients, using a primary endpoint of six-minute walk distance (6MWD) at hospital discharge.
- Body composition. To determine if the combined intervention, compared to usual care, improves amino acid utilization and decreases muscle wasting in ICU patients (secondary endpoints).
- Patient-reported outcomes and health care utilization at 6 months. To determine if the combined intervention, compared to usual care, improves physical functioning, health-related quality of life, and healthcare utilization at 6 months after study enrollment (secondary endpoints).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥18 years old.
- •Requiring mechanical ventilation with actual or expected total duration of mechanical ventilation ≥ 48 hours.
- •Expected ICU stay ≥ 4 days after enrollment (to permit adequate exposure to the proposed intervention).
排除标准
- •>96 continuous hours of mechanical ventilation before enrollment.
- •Expected death or withdrawal of life-sustaining treatments within this hospitalization.
- •No expectation for any nutritional intake within the subsequent 72 hours.
- •Severe chronic liver disease (MELD score ≥20) or acute fulminant hepatitis.
- •Documented allergy to the amino acid intervention.
- •Metabolic disorders involving impaired nitrogen utilization
- •Not ambulating independently prior to illness that lead to ICU admission (use of gait aid permitted).
- •Pre-existing primary systemic neuromuscular disease (e.g. Guillain Barre).
- •Neuromuscular blocker infusion (eligible once infusion discontinued if other inclusion criteria met).
- •Intracranial or spinal process affecting motor function
- •Pre-existing cognitive impairment or language barrier that prohibits outcomes assessment.
- •Patients in hospital >5 days prior to ICU admission
- •Lower extremity impairments that prevent cycling (e.g. amputation, knee/hip injury).
- •Remaining intubated for airway protection only
- •Weight ≥150kg
- •Physician declines patient enrollment
- •Insufficient IV access
- •Incarcerated
- •Patients with acute kidney injury (AKI) as defined by meeting any of the KDIGO criteria (below) and not receiving renal replacement therapy:
- •Increase in serum creatinine by ≥ 0.3 mg/dl within 48 hours or
- •Increase in serum creatinine to ≥ 1.5 times baseline** or
- •Urine volume <0.5 ml/kg/h for 6 hoursⴕ
研究组 & 干预措施
IV amino acid + in-bed cycle ergometry
Beginning within 96 hours of initiation of mechanical ventilation, participants will receive the combined intervention that includes IV amino acids supplementation and in-bed cycle ergometry exercise
干预措施: IV amino acids (Drug)
IV amino acid + in-bed cycle ergometry
Beginning within 96 hours of initiation of mechanical ventilation, participants will receive the combined intervention that includes IV amino acids supplementation and in-bed cycle ergometry exercise
干预措施: In-bed cycle ergometry exercise (Device)
结局指标
主要结局
Physical functioning
时间窗: Hospital discharge (up to 26 weeks after randomization)
6-minute walk distance
次要结局
- Re-intubation(Hospital discharge (up to 26 weeks after randomization))
- Physical functioning/participation - living location(Telephone survey at 6 months)
- Mental and Cognitive Functioning - HADS(Telephone survey at 6 months)
- Quadriceps force-lower extremity strength(Hospital discharge (up to 26 weeks after randomization))
- Distal strength-hand grip strength(ICU and hospital discharge (up to 26 weeks after randomization))
- Overall Physical Functional status - Short Physical Performance Battery(ICU and hospital discharge (up to 26 weeks after randomization))
- Overall Physical Functional status - Functional Status Score - ICU(ICU and hospital discharge (up to 26 weeks after randomization))
- Mortality(ICU and hospital discharge (up to 26 weeks after randomization))
- ICU stay(ICU and hospital discharge (up to 26 weeks after randomization))
- Hospital stay(ICU and hospital discharge (up to 26 weeks after randomization))
- Overall strength-upper extremity(Hospital discharge (up to 26 weeks after randomization))
- ICU readmission(Hospital discharge (up to 26 weeks after randomization))
- Health-related quality of life - EQ-5D-5L(Telephone survey at 6 months)
- Physical functioning - Lawton IADL(Telephone survey at 6 months)
- Health Care Resource Utilization(Telephone survey at 6 months)
- Overall strength-lower extremity(Hospital discharge (up to 26 weeks after randomization))
- Length of ventilation(ICU and hospital discharge (up to 26 weeks after randomization))
- Discharge location (e.g. home vs. rehab)(Hospital discharge (up to 26 weeks after randomization))
- Body composition - Ultrasound(Enrollment, hospital discharge, & ICU discharge (up to 26 weeks after randomization))
- Body composition - CT - Abdominal Scan when clinically available(Enrollment, hospital discharge, & ICU discharge (up to 26 weeks after randomization))
- Mental and Cognitive Functioning - IES-R(Telephone survey at 6 months)
- Hospital-acquired infections(Hospital discharge (up to 26 weeks after randomization))
- Body composition - CT - Chest when clinically available(Enrollment, hospital discharge, & ICU discharge (up to 26 weeks after randomization))
- Body composition - DEXA Scan(At Hospital Discharge)
- Body Composition - Heavy water(Enrollment, Days 1-7)
- NEXIS FLAME - Lung Inflammation(Enrollment, Day 5)
- NEXIS FLAME - Muscle inflammation(Enrollment, Day 5)
- Mental and Cognitive Functioning - MoCA-BLIND(Telephone survey at 6 months)
- Health-related quality of life - SF-36(Telephone survey at 6 months)
- Physical functioning - Katz ADL(Hospital discharge (proxy) and telephone survey at 6 months)
- Physical functioning/participation - return to work(Telephone survey at 6 months)
- Plasma and muscle protein synthesis - Heavy water(Enrollment, Days 1-7)
- NEXIS FLAME - Muscle area(Enrollment, Day 5)
- NEXIS FLAME - Circulating inflammatory mediators(Enrollment, Days 3, 5, and 8)
研究者
Daren K. Heyland
Director
Clinical Evaluation Research Unit at Kingston General Hospital