Clinical trial NCT04011072: Far Infrared Therapy on Arteriovenous Fistulas in Hemodialysis Patients
Official title: Effect of Far Infrared Therapy on Arteriovenous Fistulas Maturation, Survival and Stenosis. A Randomized, Controlled Open-labeled Multicenter Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Arterio-venous Fistula
Keywords: Hemodialysis
Infrared therapy
Stenosis
Maturation
Arteriovenous fistula survival
Lead sponsor: Herlev and Gentofte Hospital
Sponsor class: OTHER
Collaborators: name: Rigshospitalet, Denmark
name: Hillerod Hospital, Denmark
name: Holbaek Sygehus
name: Zealand University Hospital
First posted: 2019-07-08
Enrollment: 206
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The number of hemodialysis patients in the world are increasing. In order to receive a sufficient dialysis, the patients needs a well functioning and stable vascular access - preferably an arteriovenous fistula (AVF). Unfortunately, the AVF has a high incidence of stenosis with percutaneous trans luminal angioplasty (PTA) as the only treatment option and a short lifetime. Little do we know of how to improve the survival of the AVF.

With this study we want to explore the effect of far infrared therapy on the stenosis, maturation and survival of the arteriovenous fistula.

The investigators will divide the patients into 2 groups: A treatment group and a control group.

The treatment group will receive infrared therapy on their fistula during their dialysis session. The control group will not receive any infrared therapy.

The investigators hope to reduce the risk of stenosis in the fistula and improve the fistula survival with this treatment.

Furthermore, the investigators want to explore the change in several biochemical markers during the treatment with infrared therapy.

Detailed description: Background:

The number of hemodialysis patients in the world are increasing. In order to receive an efficient dialysis, the patient needs a well-functioning and stable vascular access. Presently there is three options: an arteriovenous fistula (AVF), an arteriovenous graft (AVG) and a central venous catheter (CVC). CVCs are associated with an increased risk of stenosis of the central vessels, thrombosis in the AVF, infections and death. AVGs are associated with increased risk of infections, stenosis in the AVG and loss of access. This is why, the AVF is the preferred vascular access. But this vascular access does not come without risks. After the creation of an AVF there is a risk of 50 % for never maturing, which means the AVF cannot be used. Furthermore, the risk of stenosis in the AVF is also high, up to 67 % of the AVFs will have a stenosis, that needs an intervention. During this time the patient needs an alternative vascular access, such as a central venous catheter, which is related to an increased risk of infection, more hospital days and death.

The maturation of the AVF depends on several patient related, but also surgically related factors. Factors such as comorbidity, female sex, length of end stage renal disease, anatomy of the vessel, surveillance after AVF placement and the operations itself have all been shown to affect the AVF maturation. Fistula stenosis emerges from an endothelial dysfunction, inflammation and smooth muscle cell proliferation leading to intimal hyperplasia and in the end stenosis. Factors such as increased blood flow, inflammation, uremia and percutaneous transluminal angioplasty has been shown to affect the stenosis, It is not well understood, which molecular mechanism are responsible for the intimal hyperplasia.

There are few and not well established studies on how to improve the AVF survival and maturation.

Far infrared radiation (FIR) is an electromagnetic radiation (heat therapy), that is given directly on the skin above the AVF. In a few single center studies in Taiwan it has been shown to decrease the risk of stenosis and increase the fistula survival and maturation. However another study is disputing this. The mechanism behind FIR and better fistula survival is not fully understood. The infrared light is supposed to have a thermal effect, which leads to vasodilatation and a non-thermal effect, which influence the endothelial function and vasodilation and thereby it may decrease the inflammation and proliferation in the fistula, primarily through the releasing of several anti-inflammatory and vasodilating factors. This is not well documented.

Hypothesis:

Treatment with FIR for 40 minutes three times a week on the patients AVF will improve the AVF survival and maturation

Method:

This study is a randomized, controlled multicenter study on western patients

There will be 2 patient categories:

1. A group (82 patients) of dialysis patients with a newly created AF
2. A group (104 patients) of dialysis patients with an existing AVF

The patients will randomly be randomized 1:1 to either the treatment group or a control group. For group 2 the patients will be block randomized according to their access flow (AF) (above or below 950 ml/min). Furthermore these patients will be stratified according to interventions in there AVF (no interventions \>/= 1 intervention) For the FIR treatment Ws Far Infrared Therapy Unit, model TY-102F (Medical device Class 11a CE0434) is being used. The patients will receive 40 minutes of infrared radiation on the skin of their fistula during each dialysis treatment for one year. The control group will not receive any FIR treatment, but will be followed according to the protocol and in line with the treatment group.

The patients will be followed until end of study or lost-to-follow-up (death, transplantations, change of renal replacement therapy, abandoned AVF, change of vascular access to CVC, consent withdrawal or if the patients moves away).

In order to explore the long term effects of FIR the patients will be followed for an extra 6 months according to the endpoints. In a subset of 2x20 patients of the randomized controlled trial we further wish to explore the influence of infrared therapy on endothelial function and inflammation during a FIR treatment session. Blood samples will be collected before and immediately after infrared treatment directly from the treatment site, since 2 needles are placed in the fistula during the dialysis treatment. The same samples will be collected in the control group and in the intervention group during the dialysis before the first infrared intervention in order to reduce the interindividual variation in the biomarkers.The changes in markers of endothelial dysfunction and inflammation during treatment and control dialysis session will be examined and compared.

Furthermore a blood sample from each patient will be collected at study start. The predictive value of the biomarkers of endothelial dysfunction and inflammation for the treatment response to infrared therapy and the prognosis for fistula maturation, stenosis and survival will be evaluated after the randomised controlled trial has ended.

Arterial stiffness (measured by Mobil-O-Graph) will also be evaluated as a marker for fistula survival and maturation.

A total of 186 participants will be recruited from 9 dialysis centres. If the study shows positive results, the implication of FIR in the clinic will have a huge beneficial effect for the hemodialysis patients vascular access and perhaps also patient survival. FIR is an easy treatment with a low cost-effectiveness and minimal or no side effects for the patient.

Eligibility criteria: Inclusion Criteria:

For incident AVF:

* Patients of 18 years of age or above
* Patients on chronic hemodialysis with a central venous catheter, who is having an AVF placed
* An AVF, that are maximum 3 weeks old

For prevalent AVF:

* Patients in chronic hemodialysis with a functioning AVF
* Patients of 18 yeas of age or above

Exclusion Criteria:

* Not obtainable informed consent
* Non compliant patients
* Patients who use both a CVC and an AVF as their vascular access
* Patient on both hemodialysis and peritoneal dialysis
* Planned living donor kidney transplantation
* Short life expectancy, less than a 1 year
* Patients on hemodialysis less than 3 times per week

Primary outcomes:
measure: Time to fistula maturation for the incident fistulae
timeFrame: After 12 months
measure: Difference in number of fistula intervention for the prevalent fistulae
timeFrame: After 12 months
Secondary outcomes:
measure: Difference in number of fistula interventions in the incident fistula group
timeFrame: After 12 months
measure: Difference in the fistula diameter in the incident fistula group
timeFrame: After 12 months
measure: Number of abandoned fistulae in incident and prevalent groups
timeFrame: After 12 months
measure: The incidence of primary patency in the incident group
timeFrame: After 12 months
measure: Number of patients with a never functioning fistula in the incident group
timeFrame: After 12 months
measure: Change in access flow in the incident and prevalent group
timeFrame: After 12 moths
measure: Baseline value in serum amyloid A as a predictor for AVF survival and stenosis
timeFrame: After 12 months
measure: Baseline value in adhesion molecules, heme-oxygenase and ADMA and selectin as a predictor for AVF survival stenosis
timeFrame: After 12 months
measure: Baseline value in von willebrand factor as a predictor for AVF survival stenosis
timeFrame: After 12 months
measure: Baseline in nitrite and nitrate as a predictor for AVF survival stenosis
timeFrame: After 12 months
measure: Baseline in different biomarkers as a predictor for AVF survival stenosis
timeFrame: After 12 months
Other outcomes:
measure: Difference in cannulation pain in the incident and prevalent group compared with visual analogue scale
timeFrame: After 12 months
measure: Difference in number with steal symptoms in the incident and prevalent group
timeFrame: After 12 months
measure: Acute changes in serum amyloid A after a single FIR treatment
timeFrame: After 40 minutes of FIR treatment
measure: Acute changes in adhesion molecules, heme-oxygenase and ADMA and selectin as a predictor for AVF survival stenosis after a single FIR treatment
timeFrame: After 40 minutes of FIR treatment
measure: Acute changes in von willebrand factor after a single FIR treatment
timeFrame: After 40 minutes of FIR treatment
measure: Acute changes in nitrite and nitrate after a single FIR treatment
timeFrame: After 40 minutes of FIR treatment
measure: Acute changes in different biomarkers after a single FIR treatment
timeFrame: After 40 minutes of FIR treatment
Locations:
city: Frederiksberg
country: Denmark
facility: Frederiksberg Hospital
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Hillerød
country: Denmark
facility: Hilleroed Hospital
city: Holbæk
country: Denmark
facility: Holbæk Hospital
city: Hvidovre
country: Denmark
facility: Hvidovre Hospital
city: København
country: Denmark
facility: Rigshospitalet
city: Nykøbing Falster
country: Denmark
facility: Nykøbing Falster Hospital
city: Roskilde
country: Denmark
facility: Roskilde Hospital
city: Slagelse
country: Denmark
facility: Slagelse Hospital
Study officials:
affiliation: Herlev Hospital, Department of Nephrology
name: Ditte Hansen, Doctor
role: STUDY_CHAIR
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