Llwynypia, United Kingdom
Trans-coronary Cooling and Dilution for Cardioprotection During Revascularisation for ST-elevation Myocardial Infarction
The study population will comprise 60 patients with ST-Elevation Myocardial Infarction (STEMI) presenting to Harefield Hospital undergoing primary percutaneous coronary intervention (PCI). The primary aim of this pilot trial is to investigate the recruitment rate feasibility and safety of undertaking a randomised trial of simple intracoronary coronary cooling and dilution through the guiding catheter during primary PCI for STEMI to reduce myocardial infarction size. The secondary aims are as follows: 1. The study will explore the invasive haemodynamic assessment of coronary flow and microvascular function 2. The study will explore blood biomarkers before and after treatment for myocardial infarction 3. The study will explore myocardial salvage after treatment for myocardial infarction with magnetic resonance imaging (MRI) and subsequent final infarct size. Patients will be randomised 1:1 in the catheterisation lab when coronary angiography has demonstrated a target lesion with proposed primary PCI. Patients randomised to the intervention will receive transcatheter cooling and dilution in addition to usual clinical care. Patients randomised to control will receive usual care alone. A combined thermistor and pressure wire Coroventis™ (Abbott Vascular) with comparable tip stiffness to standard guidewires and in routine clinical use, will be used to perform the primary PCI procedure and to measure intracoronary temperature and pressure continually throughout all procedures in all patients. This will therefore limit the procedure to a simple single wire throughout strategy in most cases. In the event that the wire fails to function properly during or after the PCI procedure it may be changed for a new wire using standard interventional techniques as appropriate Patients randomised to intracoronary cooling and dilution(n=30), will receive an intracoronary infusion of room temperature 0.9% Normal Saline solution through the guiding catheter which will commence immediately prior to crossing the coronary occlusion with the guidewire. Using a 3-way tap in the procedural manifold an infusion pressure of 150mmHg above systolic blood pressure achieved with a pressure bag will be used to achieve a target intracoronary temperature of 6-8 C° below the baseline temperature. The infusion will continue until 10 minutes after the lesion is crossed and distal flow is restored, with only brief interruptions as required for the clinical procedure. A maximum volume of 750ml will be infused. The primary angioplasty procedure itself will be undertaken according to standard local practice. Patients randomised to the control group (n=30) will undergo primary PCI according to standard local practice. A complete physiological study including Fractional flow reserve (FFR), resting full-cycle ratio (RFR), coronary flow reserve (CFR), resistive reserve ratio (RRR) and index of microvascular resistance (IMR) to assess microcirculation will be measured 10 minutes after reperfusion in all patients. Patients will go on to have blood taken on the next day for the analysis of a panel of biomarkers and comparison with pre-procedure levels and in addition to have a cardiac MRI scan prior to discharge and at 6 months.
Phase
N/ASpan
118 weeksSponsor
Royal Brompton & Harefield NHS Foundation TrustUxbridge
Recruiting
Imperial Prostate 7 - Prostate Assessment Using Comparative Interventions - Fast Mri and Image-fusion for Cancer
Background and study aims: The aim of this study is to improve the way prostate cancer is diagnosed by looking at two different types of MRI scans and two different types of prostate biopsy (tissue samples). A large study such as this is required to help the NHS decide how to diagnose prostate cancer in the future. If a person is suspected of having prostate cancer, then they are referred by their GP. At the hospital clinic, the participant will then have an MRI scan. If this scan shows that cancer might be present, then the doctor will usually suggest that the patient has a biopsy. There are two ways of doing a prostate MRI. One takes 30-40 minutes and requires a contrast injection called gadolinium (like a dye). This is called long MRI and is most commonly used in the NHS. Gadolinium is safe as it rarely causes any bad reaction but using it means that the scan takes more time. Another type of MRI takes 15-20 minutes and does not use gadolinium contrast. This is called a short MRI. Many studies over the last 5 years have shown that the long and short MRIs are similar in their accuracy in diagnosing important prostate cancer. These studies have not been of high quality or large enough to change NHS practice. Patients with suspicious areas on the MRI are usually advised to have a prostate biopsy. This involves taking tissue samples using a needle. The samples are then looked at under the microscope by a pathologist to see if cancer cells are present. There are two ways of doing a prostate biopsy. One is where the person doing the biopsy decides where to put the biopsy needle by looking at the MRI scans that have been already taken on a computer screen. The needle is guided to the prostate using live ultrasound scans that are shown on a different screen near the patient. The biopsy operator makes a judgement about where to place the biopsy needles. This is called visual registration. Tissue samples from other areas of the prostate that look normal on the MRI scans are also taken to ensure cancer is not missed. The other type of biopsy is called image fusion. During image fusion biopsy, the biopsy operator uses the MRI scans that have been taken beforehand but laid on top of the live ultrasound images during the biopsy. This uses software and takes a few minutes longer to perform. Once the MRI images and ultrasound images are 'fused', the actual biopsies are taken as normal. Studies over the last 5 years have shown mixed results. Some have shown that image fusion biopsy is no better than visual registration biopsy, whilst a few have shown it might make a difference in improving cancer detection. As a result, it is not known for certain which way is better. A large study is needed to show whether the investigators need to do image fusion or not, in order for the NHS to decide whether or not to use it in all hospitals doing prostate biopsies.
Phase
N/ASpan
170 weeksSponsor
Imperial College LondonUxbridge
Recruiting
Spirometry Interpretation Performance of Primary Care Clinicians With/Without AI Software
This is a randomised controlled study to evaluate the effects of AI support software on the performance of primary care clinicians in the interpretation of spirometry. Clinicians will be provided with a clinical dataset of 50 entirely anonymous, previously recorded real-world spirometry records to interpret and will be asked to complete specific questions about diagnosis and quality assessment. The records will be randomly selected from a database comprising spirometry records from 1122 patients undergoing spirometry in primary care and community -based respiratory clinics in Hillingdon borough between 2015-2018. Participating clinicians will be allocated at random to receive either spirometry records alone or spirometry records with the addition of an AI spirometry interpretation eport. The clinical spirometry records will be de-identified (name, date of birth, address, postcode, occupation, GP, medications data removed), by a member of the clinical care team. Study participants (participating clinicians) will independently examine the same 50 spirometry records through an online platform. For each spirometry record, the primary care clinician participant will answer questions about technical quality, pattern interpretation, preferred diagnosis, differential diagnosis and self-rated confidence with these answers. The study statistician will be blinded to treatment allocation up to completion of analysis and interpretation. The reference standards for spirometry technical quality and pattern interpretation will be made by a senior experienced respiratory physiologist but without access to AI report. The reference standard for diagnosis will be made by a panel of three respiratory specialists from the clinical care team with access to medical notes and results of relevant investigations but without access to AI report.
Phase
N/ASpan
66 weeksSponsor
Royal Brompton & Harefield NHS Foundation TrustUxbridge
Recruiting
Healthy Volunteers
Inherited Cardiac cONditions In Kids
This is a multi-centre, observational study of children with rare inherited cardiac conditions. The focus of the study will be on children with clinically diagnosed cardiomyopathy and their unaffected parents, with collection of baseline demographic data, imaging data, and genotyping data. Children and their parents will been rolled over a 5-year period. Sub-sets of patients with confirmed diagnoses of other heritable cardiovascular diseases with onset <16 years will also be recruited.These will include children who following evaluation by their clinical multidisciplinary team (which will include a geneticist or genetic counsellor) are likely to have a rare monogenic condition. Other affected family members of eligible patients may be also invited to participate in the study. Information for this study will be collected primarily from investigations performed as part of the participants' routine clinical care including whole genome sequencing commissioned by NHS England. The study will seek consent to access and export this data. Procedures performed as part of this study may include venepuncture and/or saliva collection and carry minimal risk to the patient. Parents of participants that are recruited into the study will donate a blood sample (or saliva sample if unable to provide blood) and consent will be requested for collection of health information and results of relevant investigations carried out as part of their routine clinical care (e.g. an echocardiogram). Other family members that are recruited into the study will donate a blood sample (or saliva sample if unable to provide blood) and consent will be requested for collection of health information. Family members of deceased patients with cardiomyopathy or other inherited cardiac conditions may be asked if they wish to donate stored samples that may have been taken prior to death or as part of a post-mortem examination to establish cause of death. Any discussion with regard to the use of stored samples for this project will be initiated by the clinical care team for the deceased patient and their family to minimise any potential distress to the family. Sub-sets of patients may be asked to donate tissue samples taken as part of their clinical care.
Phase
N/ASpan
222 weeksSponsor
Imperial College LondonUxbridge
Recruiting
More Singing, Less Swinging - Is Singing Related to Improved Postural Control?
Singing has become a popular arts-in-therapy activity used by physiotherapists as part of their clinical treatment. For example, Singing for Lung Health (SLH) programmes are used in the management of long-term respiratory conditions. These programmes involve group-based singing activities with a focus on breathing control and posture. There are indications that SLH is effective at alleviating symptoms of respiratory disease, likely due to a combination of physical, psychological and social mechanisms. One main factor that could directly impact on breathing are affective and attentional changes. Reduced anxiety and depression through singing therapy has been suggested to improve breathing control and functioning in those with chronic respiratory conditions. Qualitative surveys have reported that participants find singing to be an "uplifting" activity and that singing with a group of peers may also help to combat isolation. These changes may be accompanied by changes in allocation of attention. I.e., it is thought that anxiety leads to heightened vigilant monitoring of breathing, and that this hypervigilance leads to a switch in control of breathing from automatic to consciously processed, resulting in breathing dysfunction and breathlessness. Notably, normalisation of such excessive anxiety related vigilance may underpin the improvements that patients report after singing therapy, in terms of control of breathing and breathlessness during exacerbations. Singing therapy may therefore improve breathing control through reducing anxiety as well as associated attention to breathing. One aim of this study is to test this idea further, and to determine if singing impacts on breathing vigilance. An additional potentially very important effect of singing interventions is that people may improve their balance control as well, both directly and indirectly. Breathing and postural control are tightly linked. We continuously need to make postural adjustment in response to disturbances due to (changes in) breathing - and especially so when breathing is effortful and accelerated. Several studies of SLH in patients with COPD report participants perceive singing had a positive impact on their posture. Also, recent studies suggest that expert singers have better postural control compared to novices. Better control over breathing thus may also improve postural control. Indirectly, and similar to breathing vigilance, singing interventions may also help normalise individual's attention toward posture and balance. Fear of falling is common in people with respiratory conditions such as COPD. Typically, such fear / anxiety will lead to a strong, potentially excessive, increase in attention to balance. As with breathing, this "hypervigilance" can itself lead to distorted perception of unsteadiness. Singing therapy may therefore improve balance control through reducing anxiety and associated attention to movement. Therefore, this study will also explore the effects of singing on balance control and associated changes in balance-related hypervigilance. To investigate these questions, investigators planned a scoping study in which they: - Aim to investigate the effects of singing on breathing control (e.g., breathing rate, breathing pattern assessment; see all outcomes below) - Immediate: Effects of singing (varying demands) vs no-singing condition - Long-term: differences between people with and without regular singing experience in terms of breathing control during no-singing vs singing conditions. - Aim to investigate the effects of singing on breathing-related anxiety & vigilance (state anxiety, breathing vigilance; self-reported) - Immediate effects (balance vs. balance + singing) & long-term effects (differences between groups with and without singing experience) - Aim to investigate the effects of singing on balance control (sway, sway frequency) - Immediate effects (balance vs. balance + singing) & long-term effects (differences between groups with and without singing experience) - Aim to investigate the effects of singing on balance-related anxiety and vigilance (state anxiety, balance hypervigilance, conscious processing of balance; all self-reported) - Again, immediate effects (balance vs. balance + singing) & long-term effects (differences between groups with and without singing experience)
Phase
N/ASpan
59 weeksSponsor
Brunel UniversityUxbridge
Recruiting
Healthy Volunteers
Photographic Rhinometry Following Derm/Mohs Surgery for Skin Cancers
Phase
N/ASpan
98 weeksSponsor
NHS GrampianUxbridge
Recruiting
Trial to Test the Effects of Adding 1 of 2 New Treatment Agents to Commonly Used Chemotherapy Combinations
AML18 is a trial primarily for older patients with AML and high risk Myelodysplastic Syndrome (MDS). It offers a randomised controlled Phase II/III trial which uses a factorial design for maximum efficiency to evaluate two induction options followed by treatment with small molecule beyond course 1, and dose intensification for patients without evidence of MRD negativity. There are five randomised comparisons within the trial: 1. At diagnosis: For patients not known to have adverse risk cytogenetics DA chemotherapy plus a single dose of 3 mg/m2 of Mylotarg versus CPX-351. Patients with abnormal LFTs can enter the randomisation but receive DA alone or CPX-351. 2. For patients who received DA chemotherapy but are not in CR or who are MRD +ve, or for whom MRD is not assessable. DA versus DAC versus FLAG-Ida 3. All patients at second course who have received DA and have not received Vosaroxin and Decitabine induction AC220 versus no AC220 for a maximum of 3 cycles; then with or without maintenance for 1 year for patients allocated AC220 4. For patients who are in CR or CRi and MRD -ve post course1 and have completed 2 courses of DA DA versus intermediate dose Cytarabine (IDAC) 5. For patients who received CPX-351 chemotherapy but are not in CR or who are MRD +ve, or for whom MRD is not assessable CPX-351 100 units/m2 x 3 doses versus CPX-351 100 units/m2 x 2 doses The trial will also assess: - Non-intensive allogeneic stem cell transplant for patients with matched sibling or matched unrelated donors. - The combination of Vosaroxin and Decitabine for those with known adverse risk cytogenetics at diagnosis
Phase
2/3Span
383 weeksSponsor
Cardiff UniversityUxbridge
Recruiting
Myeloma XIV: Frailty-adjusted Therapy in Transplant Non-Eligible Patients With Newly Diagnosed Multiple Myeloma
Phase
3Span
230 weeksSponsor
University of LeedsUxbridge
Recruiting
Weaning Algorithm for Mechanical VEntilation
Patients admitted to the intensive care unit typically receive invasive mechanical ventilatory support when they are critically ill. Whilst mechanical ventilation is a life-saving intervention, it can also lead to deleterious consequences and cause lung damage (known as ventilator-associated lung injury) if not implemented carefully. Hence, reducing the duration of mechanical ventilation should reduce complications such as ventilator-associated lung injury, ventilator-acquired pneumonia, respiratory and skeletal muscle wasting, and patient discomfort, leading to decreasing mortality and economic costs etc. Importantly, prolonged weaning perpetuates these complications which further increase the duration of mechanical ventilation thereby creating a viscous cycle leading to greater morbidity and mortality. The availability and education of intensive care unit (ICU) staff are important considerations in minimizing the duration of mechanical ventilation through weaning protocols. It is common practice that the attending physician decides upon patient's therapy and ventilatory management according to recommendations. This usually occurs as part of medical rounds. In addition, nurses often manage the weaning of patients from mechanical ventilation either by following attending physicians' instructions or local guidelines protocols. Such protocol-directed, nurse-driven weaning has been shown to reduce the duration of mechanical ventilation. However, it has been shown that the quantity and quality of nursing are important factors if duration is to be reduced. Several decision support systems have been developed to help select optimal mechanical ventilator strategies. Those finding their way into routine clinical practice have typically been based on clinical guidelines or rules rather than detailed physiological description of the individual patient. A recent Cochrane review of weaning trials with these systems concluded that use of these systems may reduce duration of weaning, but pointed out that many of these trials are based on patients that are 'simple to wean'. Such patients are usually less complex, without lung pathology, and ventilated for less than 48 hours. However, there is a need to develop and validate protocolised systems that utilize a more detailed physiological description of individual patients to aid in the management of complex patients ventilated for longer durations. The Beacon Caresystem is a model-based decision support system using mathematical models tuned to the individual patient's physiology to advise on appropriate ventilator settings. Personalised approaches using individual patient description may be particularly advantageous in complex patients, including those who are difficult to mechanically ventilate and wean; precisely those where previous systems have not been sufficiently evaluated. The Beacon Caresystem is a commercial version of the system previously known as INVENT, which has been retrospectively evaluated in post-operative cardiac patients and patients with severe lung disease, and prospectively evaluated in advising on the correct level of inspiratory oxygen. Furthermore, studies are near completion showing that the system provides safe and appropriate advice on inspired oxygen, respiratory frequency, tidal volume, pressure support/control and positive end expiratory pressure (PEEP) in a wide variety of patients ranging from patients with severe respiratory failure to patients close to extubation (unpublished data). However, previous and ongoing studies with the Beacon Caresystem have focused on safety and efficacy of advice under limited time periods, and have not focused on weaning from mechanical ventilation. The core of the Beacon Caresystem is a set of physiological models including pulmonary gas exchange, acid-base chemistry, lung mechanics, and respiratory drive. The Beacon Caresystem tunes these models to the individual patient such that they describe accurately current measurements. Once tuned, the models are used by the system to simulate the effects of changing ventilator settings. The results of these simulations are then used to calculate the clinical benefit of changing ventilator settings by balancing the competing goals of mechanical ventilation. For example, an increased inspiratory volume will reduce an acidosis of the blood while detrimentally increasing lung pressure. Appropriate ventilator settings therefore imply a balance between the preferred value of pH weighted against the preferred value of lung pressure. A number of these balances exist, and the system weighs these, calculating a total score for the patient for any possible ventilation strategy. The system then calculates advice as to changes in ventilator settings so to as improve this score. The Beacon Caresystem functions as an "open loop" system. This means that the advice provided by the system is presented to the clinician. The ventilator settings are then changed by the clinician, and the patient's physiological response to these changes is automatically used by the system to re-tune the models and repeat the process of generating new advice. In calculating appropriate advice, selecting the correct level of positive end expiratory pressure (PEEP) is particularly challenging. The nature of the challenge is however, very different depending upon the presence or type of lung abnormality, and the function of the heart. Patients with severe lung abnormalities such as acute respiratory distress syndrome (ARDS), which often result in small, stiff lungs, are often in control ventilation mode with little or no spontaneous breathing. For these patients, PEEP is often increased to try to recruit units of the lung which are collapsed. This can be difficult, as increasing PEEP may result in elevated lung pressure and hence an increased the risk of lung injury, incomplete expiration and air trapping, and haemodynamic compromise, especially in those with heart failure. Patients in support ventilation modes have some degree of spontaneous breathing, and the correct selection of PEEP therefore includes different criteria. It is important that these patients be weaned as quickly as possible, and PEEP is reduced as part of that process. If the setting of PEEP is too low, there is a risk of increased resistance to airflow with added respiratory work and consequent risk of respiratory muscle fatigue. If the patient has intrinsic PEEP due to dynamic hyperinflation, reducing PEEP below the level of intrinsic PEEP would also cause increased inspiratory threshold load on the respiratory muscles, and potential muscle fatigue. If PEEP is too high the respiratory muscle fibres may be shortened reducing their pressure generating capacity and endurance thus increasing the risk of respiratory muscle fatigue. Changing pressure support may help to work against an additional workload, as in cases of increased resistance or autoPEEP, whilst correct PEEP may counter the additional load. The above factors are taken into account by the physiological models of the Beacon Caresystem, and patient specific advice is also provided on PEEP. In addition to providing advice on changing individual ventilator settings, the system also advises on when measurement of arterial blood gas is necessary, when it is important to change ventilator mode, and when a spontaneous breathing test is passed, and as such extubation should be considered. However, previous and ongoing studies with the Beacon Caresystem have focused on safety and efficacy of advice under limited time periods, and have not focused on weaning from mechanical ventilation. A current study is underway in a French hospital (Clinical Trials number: NCT02842944), and at a UK hospital (IRAS 226610), to assess the benefit of the Beacon Caresystem in general medical intensive care patients. However, as mechanical ventilation therapy can vary with different patient populations it is important that investigation of the effects of use of the Beacon system be studied in numerous different clinical situations. In contrast to other studies, this study will investigate the effects of the Beacon Caresystem in ICU patients with primary cardio-thoracic disease, with these patients representing a substantial sub group of all ICU patients worldwide. The purpose of this study is to compare mechanical ventilation following advice from the Beacon Caresystem to that of routine care in cardio-thoracic ICU patients from the start of requiring invasive mechanical ventilation until ICU discharge or death. The Beacon Caresystem will be compared to routine care to investigate whether use of the system results in similar care or reduced time for weaning from mechanical ventilation.
Phase
N/ASpan
158 weeksSponsor
Royal Brompton & Harefield NHS Foundation TrustUxbridge
Recruiting