Transdermal Fluid Removal In Patients with Fluid Overload
Research type
Research Study
Full title
Transdermal Fluid Removal (TFR) In Patients with Fluid Overload
IRAS ID
237781
Contact name
Leonard Ebah
Contact email
Sponsor organisation
Manchester University NHS Foundation Trust (MFT)
Clinicaltrials.gov Identifier
Duration of Study in the UK
0 years, 11 months, 30 days
Research summary
Summary of Research
Patients with conditions such as heart failure suffer from excessive fluid accumulation, causing swelling and breathing problems. Several do not respond to treatment with water pills (diuretics). They require frequent admission to hospital for intravenous diuretics and in extreme cases, dialysis. This is inconvenient for patients, sometimes has little effect and is very expensive.
This study seeks to develop a new method that will remove fluid directly from underneath the skin, where most of the excess fluid accumulates in these patients. The fluid layer in the skin will be accessed creating microscopic channels in the skin by applying and removing tiny (micro) needles on the skin. A vacuum device (i.e. a negative pressure device) will then be used to draw-up the excess accumulated fluid gradually over time, into a container. In prior studies in over 100 patients, this method has been shown to be safe and not causing pain. In some patients, up to 400ml (nearly half a litre) of fluid was removed, providing symptom relief and demonstrating the potential of this approach as a new treatment for fluid accumulation in such conditions.
This study aims to further develop the method and understand the requirements needed to develop it as a reliable future treatment option for fluid accumulation. The study participants will be adult patients with significant swelling (oedema) due to fluid accumulation from conditions such as heart failure.
Once consented, a research session of up to 10 hours will take place either at the patient's bedside or in a dedicated research room at the Manchester Royal Infirmary. Microneedles will be applied on the skin after aseptic cleaning and removed. A vacuum pressure device will then be attached to collect, gradually over time, fluid with regular monitoring by a researcher for up to 10 hours.
Summary of Results
Transdermal Fluid Removal (TFR) in patients with Fluid Overload This study on Transdermal Fluid Removal in patients with Fluid Overload was conducted at Manchester Foundation Trust (MFT). It was sponsored by MFT and received funding from Renephra Ltd, British Heart Foundation and Kidneys for Life. Due to COVID-19 pandemic, the duration of the study was longer than anticipated beginning in November 2020 and completing in March 2022.
Fluid overload is often seen in patients with vital organ dysfunction such as in kidney, liver and heart disease. Due to the patient's inability to remove excess wastes and water, these accumulate in their body fluid compartments. Current treatment options for removal of excess fluid includes water tablets, injections and in some severe cases, dialysis treatment. Beyond a certain threshold, fluid can begin to accumulate in tissues called the extracellular compartment, frequently manifesting as oedema (swelling) in dependent areas. As well impairing cell function, oedema can be distressing, reducing mobility and causing significant discomfort.
The purpose of this study was to investigate a device which could provide an additional/alternative means of removing fluid in these patients for better symptom control and improved quality of life. This novel device combines minimally invasive microneedles to access the fluid accumulating just under the surface of the skin, gently removing it under a negative pressure. We hoped to better understand both device and patient characteristics that would be important in achieving fluid removal. Finally, we wished to explore the patients experience of this new therapy.
We recruited a total of 22 patients with fluid overload, five female and seventeen male, to this study. The average age was 68 years. The main cause of fluid overload was heart failure in 59% of patients. We were able to successfully extract fluid extraction in 27% (6 patients) with a maximum volume of 16.2ml and the maximum rate of 0.21ml/hr/cm2. All patients found the procedure to be well or very well tolerated. A small number of patients were noted to have blistering (a total of 13.6% of patients) however these resolved spontaneously with no additional treatment.
We used an imaging technique called Optical Coherence Tomography (OCT) to capture the position of microneedles in the skin surface. This gave us detailed information on possible explanations as to why we were not successful in removing fluid and a greater understanding of our device limitations.
Although we were not able to demonstrate the role for large volume fluid removal using microneedle technology, fluid extraction remains feasible. To achieve consistency, a better understanding of the interaction between microneedle and human skin is essential to this novel device reaching its full potential. In this study, we have shown that Optical Coherence Tomography (OCT) can be used to determine whether the microneedles have been successfully inserted in the skin surface and, therefore, can be used to ensure consistent applications.
This study has informed researchers of the limiting factors of microneedle technology and ways in which these could be overcome in future research. A formal publication detailing the study methods and results will be available in due course.
REC name
North West - Greater Manchester South Research Ethics Committee
REC reference
19/NW/0180
Date of REC Opinion
17 Apr 2019
REC opinion
Favourable Opinion