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

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

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.

Study Overview

• Status: Completed
• Conditions: Quality of Life; Critical Illness; Chronic Kidney Diseases; Acute Kidney Injury; Muscle Loss; Major Trauma
• Intervention / Treatment: 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 Type: Observational
• Enrollment (Actual): 40

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, E11BB
    • Royal London Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Adult patients admitted to critical care.

Description

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.)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Queen Mary University of London

Publications and helpful links

General Publications

• Ravn B, Prowle JR, Martensson J, Martling CR, Bell M. Superiority of Serum Cystatin C Over Creatinine in Prediction of Long-Term Prognosis at Discharge From ICU. Crit Care Med. 2017 Sep;45(9):e932-e940. doi: 10.1097/CCM.0000000000002537.

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2018
• Primary Completion (Actual): December 1, 2021
• Study Completion (Actual): January 1, 2022

Study Registration Dates

• First Submitted: August 28, 2018
• First Submitted That Met QC Criteria: November 7, 2018
• First Posted (Actual): November 8, 2018

Study Record Updates

• Last Update Posted (Actual): September 14, 2022
• Last Update Submitted That Met QC Criteria: September 13, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Urologic Diseases; Neurologic Manifestations; Disease Attributes; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Atrophy; Kidney Diseases; Renal Insufficiency, Chronic; Wounds and Injuries; Renal Insufficiency; Muscular Atrophy; Critical Illness; Acute Kidney Injury
• Other Study ID Numbers: KRATOSProtocolv1.2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No