KRATOS: Skeletal Muscle Wasting and Renal Dysfunction After Critical Illness Trauma - Outcomes Study

Sponsor

Queen Mary University of London (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03736005

Collaborator

(none)

Enrollment

Location

28.4

Anticipated Duration (Months)

1.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study aims to determine changes in kidney function during and after critical illness, comparing conventional creatinine based methods with the gold standard to accurately establish the presence of new or worsened chronic kidney disease. In addition, investigators will assess the confounding effect of muscle wasting on the conventional assessment of kidney function and investigate the information that measures of kidney function may contribute to the assessment of musculoskeletal health after critical illness.

Condition or Disease	Intervention/Treatment	Phase
Critical Illness Acute Kidney Injury Muscle Loss Major Trauma Quality of Life Chronic Kidney Diseases	Other: Exposure of significant critical illness

Detailed Description

More people than ever are surviving life-threatening illnesses such as major trauma. However, until now doctors and researchers have focused more on improving short term survival than on the serious, long-term complications experienced by survivors of critical illness. In response, the National Institute for Health and Care Excellence (NICE) and patient-clinician partnerships such as the James Lind Alliance, have now prioritised research into the diagnosis, follow-up and treatment of critical care survivors.

Development of chronic kidney disease and persistent muscle weakness are two commonly encountered complications which significantly impact long-term health and wellbeing after critical illness. Worsening of kidney function strongly predisposes to development of heart disease, premature death or need for long-term dialysis. Similarly, the muscle wasting experienced by almost all survivors of critical illness can result in persistent, life changing limitations to daily living, inability to work and decreased quality of life. Importantly, the human and economic consequences of critical illness may be particularly profound in major trauma victims who are often young and previously healthy. In this project, investigators will aim to simultaneously measure changes in kidney function and muscle mass after critical illness allowing researchers to understand how these processes interact in affecting longer-term patient outcomes.

The investigators will recruit 62 patients, 31 admitted to intensive care after major trauma and 31 admitted for other reasons. Complementary methods will be used to accurately monitor muscle mass and kidney function. Six months after discharge from hospital, patient's ability to manage their daily activities and quality of life will be assessed alongside measurements of muscle mass, strength and kidney function. The study will be performed at the Royal London Hospital, an internationally renowned centre for critical care and trauma research.

Study Design

Study Type:

Observational

Actual Enrollment :

40 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Skeletal Muscle Wasting and Renal Dysfunction in Patients After Critical Illness and Major Trauma - Outcomes Study

Actual Study Start Date :

Dec 19, 2018

Anticipated Primary Completion Date :

May 1, 2021

Anticipated Study Completion Date :

May 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
General ICU admissions Non- major trauma ICU admission Exposure to significant period of critical illness	Other: Exposure of significant critical illness Exposure. Observational study with all patients invited to follow-up clinic for kidney, muscle and functional assessments.
Major Trauma admissions Exposure to Major Trauma Exposure to significant period of critical illness	Other: Exposure of significant critical illness Exposure. Observational study with all patients invited to follow-up clinic for kidney, muscle and functional assessments.

Arm

Intervention/Treatment

General ICU admissions

Non- major trauma ICU admission Exposure to significant period of critical illness

Other: Exposure of significant critical illness

Exposure. Observational study with all patients invited to follow-up clinic for kidney, muscle and functional assessments.

Major Trauma admissions

Exposure to Major Trauma Exposure to significant period of critical illness

Other: Exposure of significant critical illness

Exposure. Observational study with all patients invited to follow-up clinic for kidney, muscle and functional assessments.

Outcome Measures

Primary Outcome Measures

Change in estimated Glomerular Filtration Rate (eGFR) between creatinine- and cystatin C-based estimates. [At 7 days after ICU discharge.]

Secondary Outcome Measures

Rectus Femoris muscle wasting [From ICU admission (day 1 to 10) and 7 days and 6 months after ICU discharge. Time period up to and including 18 months from recruitment.]
Change in cross sectional area of Rectus Femoris assessed via ultrasound
Diagnosis of a negative Nitrogen Balance [From ICU admission (day 1 to 10) and 7 days after ICU discharge.]
Serum and urinary urea measurements aggregated as net nitrogen balance.
Respiratory muscle wasting [From ICU admission (day 1 to 10) and 7 days and 6 months after ICU discharge.]
Change in cross sectional area of intercostal muscle, change in diaphragm thickness
Loss of muscle quality [From ICU admission (day 1 to 10) and 7 days and 6 months after ICU discharge.]
Change in Rectus femoris muscle echogenecity
Loss of functional capacity [7 days and 6 months after ICU discharge.]
Change in Functional Independence Measure
Diagnosis of Anxiety of Depression [7 days and 6 months after ICU discharge.]
Change in Hospital Anxiety and Depression Scale
Diagnosis of Sarcopaenia [From ICU admission (day 1 to 10) and 7 days and 6 months after ICU discharge.]
Assessed using bioelectrical impedance analysis, change in cross sectional area of abdominal skeletal muscle,
Diagnosis of Intensive care unit acquired weakness [From ICU admission (day 1 to 10) and 7 days and 6 months after ICU discharge.]
Assessed using MRC Sum score
Diagnosis of Intensive care unit acquired weakness [From ICU admission (day 1 to 10) and 7 days and 6 months after ICU discharge.]
Assessed using hand grip strength.
Change in quality of life [pre-admission baseline then 7 days and 6 months after ICU discharge.]
Change in Euroqol 5d 5L (European quality of life group, quality of life instrument version 5D5L)
Change in walking capacity [7 days and 6 months after ICU discharge.]
Change in Six minute walk test
Diagnosis of chronic kidney disease [6 months after ICU discharge]
Diagnosis using creatinine clearance, iohexol and serum creatinine derived eGFR
Diagnosis of non-recovery of eGFR to baseline [From ICU admission (day 3 to 10) and 7 days after ICU discharge.]
Diagnosis using creatinine clearance, iohexol and serum creatinine derived eGFR

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Major trauma cohort: Patients ≥18y admitted to ICU and anticipated to be mechanically ventilated for ≥48 hours with a primary admission diagnosis of major trauma.
Non-trauma cohort: Patients ≥18y admitted to ICU and anticipated to be mechanically ventilated for ≥48 hours without a primary admission diagnosis of major trauma.

Exclusion Criteria:

Death or discharge from hospital considered highly likely by treating physician within 7 days of ICU admission.
Any of the following conditions: major traumatic brain injury (Abbreviated Injury Scale head injury score ≥ 5), spinal cord injury with paralysis, lower limb amputation, end stage renal disease or disseminated cancer, lack of independence with activities of daily living or non-ambulatory status prior to admission. (Rationale - exclusion of factors where type of injury or comorbid disease will overwhelming determine functional or renal outcomes.)