Clinical trial NCT03753412: Recovery From ICUAW Following Severe Respiratory and Cardiac Failure
Official title: Prospective Observational Study Regarding the Determinants of Functional Disability and Quality of Life in Patients Recovering From Severe Acute Cardiac or Respiratory Failure Considered for Mechanical Cardiorespiratory Support (CLEVERER)
Study type: OBSERVATIONAL
Overall status: RECRUITING
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)
Lead sponsor: Barts & The London NHS Trust
Sponsor class: OTHER
Collaborators: name: Queen Mary University of London
First posted: 2018-11-27
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

Detailed description: To identify determinants of recovery from ICUAW and to discover the effects of ICUAW on physical function and health-related quality of life (HRQoL) after critical illness. This phenomenon has become more evident over recent years and still requires extensive research.

ICUAW is an umbrella term for more specifically polyneuropathy and myopathy. Recent research has found that 50% of patients undergoing elective cardiac surgery lose significant muscle mass (9.6% in the wasters group) within the first seven days. These patients are receiving relatively uncomplicated surgery yet still suffering from muscle breakdown, which cannot be described by inactivity alone. The investigators wish to observe ICUAW in a real-life context, however, where cases are always severe. ICUAW can lead to a significant increase in mortality and morbidity. Risk factors for ICUAW include neuromuscular blocking agents, hyperglycaemia, inactivity and sepsis. The correlation between a patient group with severe cardiorespiratory failure and patient-centred outcomes during recovery such as functional ability and health-related quality of life (HRQoL) has been little studied.

Severe cardiac and respiratory failure can both be supported by a mechanical cardio-respiratory support (MCS) including extra-corporeal membrane oxygenation (ECMO); therefore referral for this intervention can be used as a marker of the severest form of cardiorespiratory failure. Both conditions are associated with a high incidence of collateral multi-organ dysfunction and mortality; as well as long-term morbidity, loss of independence and reduced quality of life. Patients with acute cardiac and respiratory failure referred to St Bartholomew's hospital for consideration of MCS will be recruited by advice/guidance from a personal and professional consultee.

Rectus femoris cross-sectional area (RFcsa) will be measured by ultrasound during the first week of admission and at pre-determined time points. The RFcsa will be correlated with indices of muscle strength, physical function and HRQoL. The investigators will also take blood and urine samples on arrival and at pre-defined intervals during the patients' admission for circulating and respiratory markers of sepsis, oxidative stress and organ injury. A muscle biopsy will be taken from the operation field if the patient is centrally cannulated when initiating ECMO.

The primary Objective is to identify determinants of recovery from ICUAW and to discover the effects of ICUAW on physical function and health-related quality of life (HRQoL) after severe cardiorespiratory failure. Specifically, to observe the cross-sectional area of the Rectus Femoris (RFcsa) and correlate this with muscle strength and HRQoL during recovery. RFcsa, hand-held dynamometry, knee straightening dynamometry, Free Fat Mass Index, standing and lying vital capacity, MRC-SS sum score and short physical performance battery (SPPB) will be observed. Also, HRQoL will be measured using the reintegration to normal living index (RNLI), hospital and anxiety depression score (HADS)and the EQ-5D-5L (EuroQol research foundation). Additionally, we have composed a 10 item questionnaire to assess pre-morbid functional status. The primary endpoint will be once all these data are gathered and analysed.

The secondary aim is to understand the molecular and genomic profile of blood samples and the histology of the muscle biopsies. The objective will be supported with additional data from urine analysis (albumin-creatinine ratio) and vascular endothelial cells. The secondary endpoint will be once these data are collected and analysed.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion criteria:

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

Primary outcomes:
measure: To observe the change in cross sectional area of the Rectus Femoris (RFcsa, measured in cm2) during critical illness and recovery.
timeFrame: Up to approximately 1 year.
measure: To Observe a change in Hand Held Dynamometry strength and correlate this with RFcsa, function and HRQoL during critical illness and recovery.
timeFrame: Up to approximately 1 year.
measure: 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.
timeFrame: Up to approximately 1 year
measure: To test the Medical Research Council Sum Score (MRC-SS). MRC-SS measures global strength and ambulation
timeFrame: Up to approximately 1 year.
measure: To observe a change in Short Physical Performance Battery (SPPB) and correlate this with RFcsa, function and HRQoL during critical illness and recovery
timeFrame: Up to approximately 1 year.
measure: Lying and Standing Vital Capacity (FVC - forced vital capacity) and correlate this with RFcsa, function and HRQoL during critical illness and recovery.
timeFrame: Up to approximately 1 year
measure: To measure a change in Free Fat Mass Index (FFMI) and correlate this with RFcsa, function and HRQoL during critical illness and recovery.
timeFrame: Up to approximately 1 year
measure: To measure the EQ-5D-5L (Euroscore) to assess general health and correlate this with the primary objective (RFcsa).
timeFrame: Up to approximately 1 year
measure: Hospital anxiety and depression score (HADS) to assess HRQoL and correlate this with the overall primary objective (RFcsa).
timeFrame: Up to approximately 1 year
measure: Reintegration to normal living index (RNLI) to assess HRQoL and correlate this with the overall primary objective (RFcsa).
timeFrame: Up to approximately 1 year
measure: 10-item questionnaire to assess HRQoL (pre-morbid functional status) and correlate this with the overall primary objective.
timeFrame: Day 0 (on admission)
Secondary outcomes:
measure: The secondary aim is to understand the molecular profile (bloods).
timeFrame: Up to approximately 1 year
measure: Urine Analysis
timeFrame: Up to approximately 1 year
measure: Muscle Biopsy
timeFrame: Intra operatively
measure: Vascular endothelial cell sampling
timeFrame: Day 0.
measure: Cardiac post operative morbidity score (C-POMS) will be used to calculate total morbidity risk.
timeFrame: Time Frame: Day 3, day 5, day 8 and day 15 post ECMO initiation.
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: St Bartholomew's hospital (Barts NHS trust)
Study officials:
affiliation: Substantive Employee and primary supervisor to PhD student
name: Mark Griffiths, PhD FRCP
role: PRINCIPAL_INVESTIGATOR
affiliation: Director of research and supervisor to PhD student
name: Julie Sanders, MSc, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Substantive employee and PhD student
name: Ashley Thomas, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.