Recovery From ICUAW Following Severe Respiratory and Cardiac Failure

NCT03753412 | Recruiting

• 1 other identifier: 012370 CLEVERER
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

To observe and identify determinants of recovery from intensive care unit-acquired weakness (ICUAW) following a severe cardiorespiratory failure requiring extra-corporeal membrane oxygenation (ECMO). Additionally, to discover the effects of ICUAW on physical function and health-related quality of life (HRQoL) after critical illness. CLEVERER is a clinical observational pilot study.

Conditions

Intensive Care Unit Syndrome; Intensive Care Neuropathy; Intensive Care (ICU) Myopathy; Acute Respiratory Distress Syndrome; Cardiac Failure; Respiratory Failure; Critical Illness Myopathy

Keywords

Extra Corporeal Membrane Oxygenation (ECMO); Intensive Care Unit Acquired Weakness (ICUAW); Critical Illness Polyneuromyopathy (CIPM); Ultrasound (US); Health Related Quality of Life (HRQoL)

Outcome Measures

Primary Outcomes (11)

• To observe the change in cross sectional area of the Rectus Femoris (RFcsa, measured in cm2) during critical illness and recovery.

  RFcsa will be calculated using B-mode ultrasound (US) at pre-determined time points. Additionally, the images acquired will have histogram analysis in adobe photoshop software. The RFcsa will be correlated with indices of muscle strength and HRQoL. A larger RFcsa with reduced pixel density suggests greater muscle quality and function.

  Up to approximately 1 year.

• To Observe a change in Hand Held Dynamometry strength and correlate this with RFcsa, function and HRQoL during critical illness and recovery.

  Hand-held dynamometry will be calculated using the JAMAR hand-held hydraulic dynamometer. We will assess both hands and take the mean of 3 trials, producing a maximal grip result. A higher score indicates better global strength and function.

  Up to approximately 1 year.

• To observe a change in Knee straightening dynamometry, strength and joint moment (torque) and correlate this with RFcsa, function and HRQoL during critical illness and recovery.

  The test will be conducted using a Lafayette Manual Muscle Tester. Joint knee moment (torque) and strength will be measured. A higher result from joint knee moment and strength indicates a greater global strength and function.

  Up to approximately 1 year

• To test the Medical Research Council Sum Score (MRC-SS). MRC-SS measures global strength and ambulation

  This test will be conducted once to reaffirm whether patients' have ICUAW. A score can range from 0 (paralysis) to 60 (normal strength). A score of less than 48 indicates the patient has ICUAW. Therefore, a lower score is associated with worse outcomes.

  Up to approximately 1 year.

• To observe a change in Short Physical Performance Battery (SPPB) and correlate this with RFcsa, function and HRQoL during critical illness and recovery

  SPPB will be used as a further marker of functional status. The patient can score between 0 (poor functional status) and 12 (good functional status).

  Up to approximately 1 year.

• Lying and Standing Vital Capacity (FVC - forced vital capacity) and correlate this with RFcsa, function and HRQoL during critical illness and recovery.

  Lying and standing vital capacity will be measured using a hand held spirometer. The test score will be compared to the predicted normal value based on age, height, race and gender. A result is considered normal if it is 80 percent or more of the predicted value.

  Up to approximately 1 year

• To measure a change in Free Fat Mass Index (FFMI) and correlate this with RFcsa, function and HRQoL during critical illness and recovery.

  Free fat mass index (FFMI) and free fat mass (FFM) will be measured using the bodystat 1500 device. Other values will also be recorded from the test including body fat percentage and lean mass percentage. The body stat 1500 is an electrical device that uses electrical impedance to obtain results (objective data). Results will be compared to predicted values based on age, sex, height and weight.

  Up to approximately 1 year

• To measure the EQ-5D-5L (Euroscore) to assess general health and correlate this with the primary objective (RFcsa).

  EQ5D-5L is a standardised tool that provides a simple generic measure of health. A summation of all the levels will be converted to a single index value using the EQ5D-5L crosswalk index value calculator. The general health score can range from 0 (worst health imaginable) to 100 (best health imaginable). Additionally, a health state ranging from level 1 (indicating no problem) to level 5 (indicating extreme problems) can be calculated using the descriptive system and its five dimensions.

  Up to approximately 1 year

• Hospital anxiety and depression score (HADS) to assess HRQoL and correlate this with the overall primary objective (RFcsa).

  The HADS is an assessment that measures whether a patient is suffering from anxiety or depression. HADS is a self assessment consisting of 16 items. A result between 0 and 7 indicates a normal case, between 8 and 10 indicates borderline abnormal and between 11 and 21 indicates abnormal levels of anxiety and depression.

  Up to approximately 1 year

• Reintegration to normal living index (RNLI) to assess HRQoL and correlate this with the overall primary objective (RFcsa).

  The RNLI is a 5 domain 11-tool item aimed at assessing the degree to which patients' who have experienced traumatic and incapacitating illness achieve reintegration into society. The RNLI score is based out of 110, which will be proportionally converted to create a score of 100. Zero indicates no integration whereas 100 implies full integration.

  Up to approximately 1 year

• 10-item questionnaire to assess HRQoL (pre-morbid functional status) and correlate this with the overall primary objective.

  This is a locally devised questionnaire that is answered by the patients' next of kin due to them being incapacitated. We will correlate these results with the other HRQoL questionnaires.

  Day 0 (on admission)

Secondary Outcomes (5)

• The secondary aim is to understand the molecular profile (bloods).

  Up to approximately 1 year

• Urine Analysis

  Up to approximately 1 year

• Muscle Biopsy

  Intra operatively

• Vascular endothelial cell sampling

  Day 0.

• Cardiac post operative morbidity score (C-POMS) will be used to calculate total morbidity risk.

  Time Frame: Day 3, day 5, day 8 and day 15 post ECMO initiation.

Study Arms (1)

ICUAW ECMO group

The physical and psychological effects of ICUAW on patients receiving extracorporeal membrane oxygenation for severe cardiorespiratory failure will be observed. Physical function and HRQoL will be analysed and correlated with RFcsa. Additionally, biological markers will be used to understand molecular and genomic profiles.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adults with severe cardiac or respiratory failure requiring extra-corporeal membrane oxygenation with no pre-existing muscle weakness or wasting.

You may qualify if:

• Above the age of 18
• Adults with severe cardio-respiratory failure requiring ECMO.
• Adults who have had personal and professional consultees agree to enrol them in the trial.

You may not qualify if:

• Previous Stroke
• Neuromuscular disease
• Malignancy
• Underlying neuromuscular disease
• paediatrics

Sponsors & Collaborators

• Barts & The London NHS Trust: lead
• Queen Mary University of London: collaborator

Study Sites (1)

St Bartholomew's hospital (Barts NHS trust)

London, EC1A 7BE, United Kingdom

RECRUITING

Related Publications (1)

• Bloch SA, Donaldson AV, Lewis A, Banya WA, Polkey MI, Griffiths MJ, Kemp PR. MiR-181a: a potential biomarker of acute muscle wasting following elective high-risk cardiothoracic surgery. Crit Care. 2015 Apr 7;19(1):147. doi: 10.1186/s13054-015-0853-5.

  PMID: 25888214 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Muscle Biopsies will be taken for histology examination at the time of surgery if the patients are centrally cannulated. Blood samples will be collected at specific time points to assess for mediators and markers of oxidative stress injury (e.g. 8-isoprostane), inflammation (e.g. interleukin-6 and soluble tumour necrosis factor receptor) and injury to multiple organs will be quantified. Urine will be collected to assess albumin-creatinine ration (ACR). Vascular endothelial cells will be analysed for cell culture and profile.

MeSH Terms

Conditions

Muscular Diseases; Respiratory Distress Syndrome; Heart Failure; Respiratory Insufficiency

Condition Hierarchy (Ancestors)

Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Heart Diseases; Cardiovascular Diseases

Study Officials

• Mark Griffiths, PhD FRCP

  Substantive Employee and primary supervisor to PhD student

  PRINCIPAL INVESTIGATOR

• Julie Sanders, MSc, PhD

  Director of research and supervisor to PhD student

  PRINCIPAL INVESTIGATOR

• Ashley Thomas, MSc

  Substantive employee and PhD student

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mark Griffiths, PhD FRCP

CONTACT

07875999126; Mark.griffiths@bartshealth.nhs.uk

Ashley Thomas, MSc

CONTACT

07597875857; ashleythomas@nhs.net

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2018
• First Posted: November 27, 2018
• Study Start: April 9, 2019
• Primary Completion (Estimated): September 26, 2026
• Study Completion (Estimated): September 26, 2026
• Last Updated: January 7, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)