The aims of the MuST Study are to:
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Determine the AVF survival of patients submitted to MuST compared to those submitted to RL.
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Determine the AVF complication rate of patients submitted to MuST compared to those submitted to RL.
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Analyze the intensity of pain perceived by the patient with each cannulation technique under study.
Study hypotheses
This study examines the following hypotheses:
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- Does MuST allow 10% rate of greater AVF survival in patients on a regular HD program in private HD clinics than RL?
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- Does MuST have a lower AVF complication rate in patients on a regular HD program in private HD clinics than RL?
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- Do patients submitted to MuST perceive less pain than patients submitted to RL?
Study population
Recruitment of the study population
Patients with end-stage kidney disease (ESKD) on a regular HD program will be recruited in 3 private dialysis clinics operating in Portugal. Decision on a study participation is made by the patient. The treading physician will inform the patient about the study and provides written information. If the patient is not willing to participate in the study by giving its written informed consent, the patient cannot be included in the study.
The patients who signed the informed consent and meet the inclusion and exclusion criteria, will be randomly organized into two groups – intervention and control groups. Each group will be stratified according to the following criteria: diabetes and AVF vintage to ensure that these variables is properly represented in the sample and avoid bias.
Inclusion criteria
Patients with AVF will be selected when:
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Are on a regular HD program with three weekly sessions;
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AVF has been in use for at least 8 weeks without incident;
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AVF with blood flow (Qa) ≥ 500 mL/min evaluated by thermodilution;
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AVF paths allow cannulations along the entire length of the vein with at least 6 cm of distance between bevels, or two distinct areas of 3 cm in length;
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Adult patients
Exclusion Criteria
Patients with the following characteristics will be excluded:
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Those who decline to take part;
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Those who have undergone angiography or surgical intervention in the last 4 months in the AVF in use;
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Those who have undergone three or more interventions in the AVF in use;
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Those with use of anesthetic creams at cannulation sites.
Intervention
For the study implementation, the key VA person and the principal investigator in each clinic will be involved and the following procedures will be carried out:
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Identification of all patients with AVF;
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Selection of eligible patients;
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Informing potential participants about the study and requesting informed consent;
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Participants’ randomization in a 1:1 ratio, according to MuST versus RL. Randomization will be performed centrally by the project manager and electronically using random sequence generator, two branches (columns) from RANDOM.ORG.
The key VA person and the nurse’s team will be carried out the following steps:
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Collect AVF photo, before the start of the study (baseline), at 6 months and at 1 year during the study;
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MuST cannulation technique – select and identify cannulation sites with a dermographic pen until their location is easily visible due to skin depigmentation; Two areas of arterial and venous cannulation will be created, with three cannulation points each at least 1 cm apart;
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Rope-ladder cannulation technique – create a diagram of the cannulation sites’ orientation. The diagram will be attached to each patient’s dialysis file for quick reference;
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AVF physical examination before each HD treatment with recording of the findings;
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The daily results of each patient’s assessment will be recorded using the computer tool VASACC (vascular access) and on an Excel spreadsheet;
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The nurse who performs the cannulation will assess the intensity of pain perceived by the patient;
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Pain will be assessed immediately after cannulation of the arterial and venous area according to the 10 cm long visual analog scale (VAS) which has the classification “No Pain” on the far left and “Extreme Pain” on the right [4, 17, 21];
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Whenever there is a referral to the Vascular Access Center (VAC) for angiography or vascular surgery, a record will be made in the patient’s clinical file in the EUCLID database;
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After the intervention in the VAC, a record of the intervention per patient will be made in the Vascular Access OnLine database (AV OnLine). This registration will be performed by the nephrologist or vascular surgeon, depending on which intervention is performed. This information will then be transcribed into the Excel data collection Spreadsheet;
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Patients will be followed until access thrombosis, abandonment due to AVF dysfunction or surgical intervention with anastomosis alteration, patient abandonment from the study, transfer to another clinic, hospitalization, death, change of treatment modality or study end;
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For the variable pain intensity, time to hemostasis, peri-needle bleeding, Qa, dialysis dose (spkt/V) and substitution volume will be evaluated at 3 time periods only: before study start, at 6 months, and at 12 months;
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Presence of scab at the cannulation site and the ease of identifying the cannulation site will be evaluated at the same time periods, but only for CT MuST;
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Monthly meetings will be held with the head nurse and key VA person, and additional meetings whenever necessary. All situations deviating from normality there will be discussed. Verification and collection of data.
In this clinical trial, we use a new fistula approach, because of which it is necessary to carry out training and raise awareness of nurses to assess and record the variables under study. Thus, it is not possible to blind the participants nor the nurses who perform the intervention.
Physicians performing angioplasty or vascular surgery will not be aware of the selected patients.
We will involve more than forty nurses, more than two hundred patients and ultimately, this can lead to improved evidence on fistula preservation.
Study Outcomes
Primary outcome
As a primary indicator, we consider AVF survival rate at 12 months and determined by the percentage of fistulas in use from the time-zero of study enrollment to the date of the first clinical intervention by angioplasty or vascular surgery, to maintain or restore patency – "unassisted patency" [15, 16].
To assess the variable "AVF survival" we consider the following criteria:
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- Fistula that is successfully cannulated with two needles, arterial and venous, that allows a prescribed blood flow of at least 300 mL/min and that allows for an adequate treatment will be considered a functioning AVF [17];
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- Fistula used without success will be considered a dysfunctional AVF, whether it has patency or not [15];
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- It will be considered AVF abandonment on the day that access is considered permanently unusable or not suitable for cannulation [17];
Referral for endovascular intervention [15, 16] will be based on two of the following factors of AVF dysfunction:
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- Decreased AVF blood flow (Qa) (assessed by thermodilution and <400 mL/min);
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- Increased hemostasis time (>10 min);
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- Cannulation failure: failure or inability to insert dialysis needles [17];
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- Decreased dialysis efficacy: low HD dose, spKt/V <1.2 [17] or substitution volume <21L. A parameter to quantify the HD adequacy (spKt/V) will be calculated based on ionic dialysance obtained by the integrated module Online Clearance Monitor (OCM®) from the 5008 CorDiax machine, and “V” was derived from total body composition assessment with a bioimpedance device (Body Composition Monitor - FMC) [18];
Or changes in the physical examination (changes in thrill, abnormal development of aneurysm, or progressive increase in edema in the AV limb) and plus one of the factors described above.
Referral for surgical intervention [15] will be based on one or more indicators of AVF dysfunction:
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- Rupture of the AVF wall;
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- AVF thrombosis;
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- Progressive development of aneurysm;
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- Acute bleeding: AVF bleeding requiring surgical intervention;
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- Local infection of the AVF;
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- Deficient distal perfusion with signs of ischemia.
Secondary outcome
We will evaluate the assisted primary patency. As an outcome, we considered AVF survival rate at 12 month and determined by the percentage of fistulas in use from the time-zero the study enrolment, to the date of access abandonment due to dysfunction, patient abandonment, or death, treatment change modality or study end [15, 17, 19]. For the study, we will consider the frequency of interventions, both endovascular and surgical, to maintain functioning access [17].
We will also include the following secondary outcomes associated with cannulation:
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- Inflammation signs at the AVF cannulation site, defined by the presence of one or more signs: redness, edema or local exudate [4];
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- AVF local infection, defined by the presence of exudate at the cannulation site with a positive bacteriological culture;
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- Bacteremia related with AVF and confirmed with a positive blood culture (describe if swab was performed and/or infection treated with antibiotics);
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- Hematoma or infiltration: an incident that occurs during cannulation that can result in local infiltration, edema, or pain, which can be treated with local ice, but re-cannulation is possible [16];
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- Time to hemostasis: time to stop bleeding after needle removal, with up to 10 min considered normal [4];
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- Peri-needle bleeding: bleeding from the puncture site during treatment and requiring nursing intervention;
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- Aneurysm development: segment dilatation of the arterialized vein at three times the diameter of the segment considered normal, which means a segment with a width of ≥ 18 mm [20]. An increase in the existing aneurysm will be considered when the vein presents an increase in its diameter of ≥ 5 mm.
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- Local pain related to CT;
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- Presence of scab at the cannulation site;
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- Easy to identify cannulation site.
Outcome parameters
For the sample characterization, we will describe the sociodemographic characteristics, comorbidities and laboratory data immediately before the start of the study (baseline). We will also describe the interventions already carried out in active AVF within the last year (T0).
Data collection instrument
Patient baseline; Follow-up data changes; Follow-up data semester; AVF intervention and Outcome.
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The data resulting from the evaluations will be collected from the VASACC and EuCliD databases and recorded on the Excel data collection Spreadsheet.
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A computer file will be created to store the patient’s VA photos. Each photo will be given an identification number.
Data usage
Pain assessment scale:
Pain will be assessed immediately after cannulation of the arterial and venous area according to the 10 cm long visual analog scale (VAS) which has the classification “No Pain” on the far left and “Extreme Pain” on the right [4, 17, 21].
The values obtained will later be registered on the Excel data collection Spreadsheet.
Statistical analysis
Data will be analyzed according to the “intention-to-treat” [15]. The continuous variables of the “baseline” will be expressed through measures of location, dispersion and the categorial variables will be summarized using absolute and relative frequencies. Descriptive comparisons and tests will be performed between groups at baseline, at 6 and 12 months. To compare two groups by continuous variables, parametric tests will be used, namely the t-test, or nonparametric tests if normality is not assumed.
To analyse relationship between categorical variables, the Chi-square test (χ2) will be conducted, or Fisher’s exact test when appropriate.
The primary factors to assess fistula survival will be calculated over time from baseline to time requiring intervention (no patency assistance) or withdrawal from the study. In this case we will use the Kaplan–Meier survival curves.
For secondary factors, such as the frequency of hematoma, signs of infection, local infection or bacteremia, and thrombosis, the number of events per 1000 days of AVF will be calculated [16].
Results will be considered significant when p < 0.05. All the statistical analysis will be performed using SPSS (version 23; IBM, Armonk, NY, USA).