Clinical trial NCT03406494: Efficacy and Safety of a Multicomponent Physical Therapy Program in Mechanically Ventilated Patient With Sepsis
Official title: Southern Medical University Clinical Research Project Initiative：Efficacy and Safety of a Multicomponent Physical Therapy Program in Mechanically Ventilated Patient With Sepsis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Sepsis
Keywords: sepsis
critical illness
intensive care unit
mechanical ventilation
rehabilitation
mortality
physical function
health-related quality of life
Lead sponsor: Zhujiang Hospital
Sponsor class: OTHER
Collaborators: name: Southern Medical University, China
First posted: 2018-01-23
Enrollment: 800
Sex: ALL
Minimum age (years): 16
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: prospective, multicenter, assessor-blinded, randomized controlled trial
Primary purpose: PREVENTION

Brief summary: Despite of a remarkable decrease in overall mortality has been achieved following the International Guidelines for Management of Sepsis and Septic Shock since 2004,the short-and long-term outcomes remain poor in critically ill sepsis patients who had experienced prolonged ventilation in the Intensive Care Unit (ICU). The reason could be due to some subsequent complications developed in the ICU rather than original disease, e.g., ICU-acquired weakness (ICUAW), delirium, diaphragmatic dysfunction (DD) and acute gastrointestinal (GI) injury, which are still not fully recognized or dealt with in a majority of ICU settings across China. This study is aimed to examine whether a multi-component physical therapy (PT) program against these lethal ICU-related complications could reduce ICU 28-day mortality, improve independent functional status and 1-year survival in this subset of patients.

Detailed description: The study is a prospective, multi-center, assessor-blinded, randomized controlled trial and will be conducted in 9 medical ICUs at 7 tertiary hospitals in Southern China. Mechanically ventilated septic patient admitted into ICU will be screened for eligibility into the study. When medically stable, patients randomize into the intervention group will receive a multi-component PT. The PT program is designed to counteract ICUAW, delirium, DD and acute GI injury, and consists of 5 consecutive sessions including positioning, extremities muscle strength training, respiratory muscle strength training, neuromuscular electrical stimulation (NMES) and gut rehabilitation. Each PT session will last for 30 minutes and be provided once daily, 5 days per week, and tailored for each individual subject. PT intervention will continue throughout patient's ICU stay or the primary endpoint is reached. The primary outcome will be the ICU 28-day all-cause mortality, and the secondary outcome measures, e.g., incidences or duration of ICUAW, delirium, DD and acute GI injury, mechanical ventilation outcomes (ventilator dependence, ventilator-free days), adverse events, restoration to independent functional status and long-term survival, will be assessed at preset time points of interviews during periods of treatment and 1-year follow-up after discharge from hospital. The total in-hospital and re-hospitalization costs in the intervention group will be also analyzed and compared to control group to assess the cost-effectiveness of the rehabilitation program.To our knowledge, this study is the first randomized controlled trial examining the efficacy and safety of a multi-component PT program in critically ill sepsis patients on ventilator. Given that rehabilitation is not a routine therapy across most ICUs in China, If this PT program is found to be of mortality benefit, it will provide an alternative non-pharmaceutical approach to deal with these lethal ICU-related complications and reduce the subsequent death. It will also provide useful information for clinical decision and local medical policies making, as well as identifying sepsis patient population who might best benefit from early rehabilitation program.

Eligibility criteria: Inclusion Criteria:

1. Diagnosed with sepsis in accordance with the Sepsis-3 Criteria.
2. 16 ≤ age ≤ 75 years.
3. Mechanically ventilated for less than 72 hours at recruitment and expected to continue for at least 3 days.
4. Ability to obtain informed consent from patient or proxy.

Exclusion Criteria:

1. acute central nervous system disease (e.g. severe cerebral injury, acute cerebral hemorrhage, brain infarction).
2. active neuromuscular diseases that limiting patient to physical training (e.g. amyotrophic lateral sclerosis, multiple sclerosis, myasthenia gravis, polymyositis, muscular dystrophy).
3. severe thoracic or abdominal trauma.
4. acute myocardial infarction, severe arrhythmia, acute heart failure, hemo-dynamic instability or shock.
5. drug abuse, alcohol addiction, opiates or other drug dependence and psychiatric disorder history.
6. known pregnancy.
7. malignant tumor, cachexia, end stage of chronic illness.
8. contraindications to rehabilitation therapy.
9. inability to obtain an informed consent from patient or a proxy.
10. any other factors such as fractures or limb malformation, that would prevent response to physical exercise or cause injury to the patient.

Primary outcomes:
measure: ICU 28-day mortality
timeFrame: Through 28-day study period in the ICU.
Secondary outcomes:
measure: Incidence of ICU-required weakness
timeFrame: Assessed on the day of recruitment, repeated on the days of first try to wean from ventilator, ICU discharge and hospital discharge, with an average of 1 month.
measure: Incidence of delirium
timeFrame: Assessed on the day of recruitment, repeated on the days of first try to wean from ventilator, ICU discharge and hospital discharge, with an average of 1 month.
measure: Incidence of diaphragmatic dysfunction
timeFrame: Assessed on the day of first try to wean from ventilator, repeated on the days of ICU discharge and hospital discharge, with an average of 1 month.
measure: Incidence of acute gastrointestinal injury
timeFrame: Assessed on the day of recruitment, repeated on the days of first try to wean from ventilator, ICU discharge and hospital discharge, with an average of 1 month.
measure: Ventilator dependence
timeFrame: Number of days required to weaning after the first try, number of days on ventilator, assessed within an average of 3 weeks.
measure: Adverse events
timeFrame: Through physical therapy periods, an average of 1 month.
measure: Length of stay
timeFrame: From admission to ICU discharge and hospital discharge, estimated between 4 to 6 weeks.
measure: Independent functional status
timeFrame: The 3rd, 6th and 12th months of 1-year follow up after hospital discharge.
measure: Health-related quality of life (HRQOL)
timeFrame: The 3rd, 6th and 12th months of 1-year follow up after hospital discharge.
measure: One-year mortality
timeFrame: One year.
Other outcomes:
Locations:
Study officials:
affiliation: Zhujiang Hospital
name: Yan Zhang
role: STUDY_DIRECTOR
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