Placement Of Cardiac PacemaKer Trial (POCKET)-RCT
Placement Of Cardiac PacemaKer Trial (POCKET)-RCT
Aim: To compare patient satisfaction with intramuscular placement of a pacemaker pocket to
 subcutaneous placement.

 Patients will be randomized (approximately half i each group) to receive the pacemaker device
 either subcutaneously (current practise) or intramuscular)
Background: Implantation of a cardiac pacemaker may be indicated in patients with a
 significant bradycardia according to current guidelines.1 Annually, around 691 pacemakers per
 million inhabitants are implanted in Sweden.2 A pacemaker system consist of one or two leads
 connected to a device that is implanted beneath the collarbone.3,4 Vessel access is typically
 on the left side through the cephalic, axillary or subclavian vein. The pacemaker is inserted
 into a pocket. Routinely this pocket is just above the pectoral fascia (subcutaneously) or
 sometimes in skinny patients with a small amount of subcutaneous fat between the pectoral
 muscular layer (intramuscular). Even though technical developments have diminished the size
 of pacemakers markedly over time, complications due to superficial implants still do
 occur.5,6 Occasionally the device erode the skin and a complete extraction of the system is
 necessary. More frequently patients complain about the device being too superficial which
 sometimes require surgical repositioning of the device.5,6 The device may create discomfort,
 pain, and unsightly.5,6 The lateral corner of the device may disturb the shoulder movement,
 sleep and the leads can be turned within the pocket (Twiddler's syndrome). Minor branches
 from the supraclavicular nerves may result in discomfort. When vessels from the subcutaneous
 adipose tissue are distorted, extensive bruising may be bothersome and a large hematoma is a
 known risk of infection. The perfusion in the operation area is diminished and the amount of
 fat over device may be reduced to an extent that was unexpected at first implant. The change
 of device due to battery depletion can result in even less surrounding tissue. An alternative
 approach is an intramuscular placement of the device.7,8 This has been advocated by Kistler
 et al based on personal experience but there are neither systematic observational studies nor
 randomized controlled studies to support this approach.6 To the knowledge of the
 investigators no randomized controlled trial have addressed the question about the optimal
 placement of a bradycardia pacemaker.

 Aim: To compare patient satisfaction with intramuscular placement of a pacemaker pocket to
 subcutaneous placement.

 Research questions: Primary outcome: Is there a different in patient overall satisfaction (on
 a Visual Analog Scale (VAS)-scale between 0-10) with the pocket between patients with
 intramuscular placement of a pacemaker pocket and patients with subcutaneous placement at 24
 months after implant? Secondary outcomes: Complications (revision of pocket, dislodgement,
 hematoma requiring surgery, infection (local/systemic). Patient reported satisfaction at 1,
 12, 24 months (overall satisfaction, pain, discomfort, degree of unsightly look, movement
 problems due to device, and sleep problems due to device). Pacemaker nurse judgement of
 unsightly look of the pacemaker pocket (month 1, 12, and 24). Picture of pocket (1, 12, 24
 months) judged by an experienced implanting physician who is blinded to the group allocation
 and has not operated on the patient.

 Method: Power analysis: the investigators performed a power analysis based on expectations
 and clinical experience of the research group. Figure 1 shows two hypothetical truncated
 lognormal distributions of patient overall satisfaction with the pacemaker, where median
 overall satisfaction of the intramuscular and the subcutaneous group are assumed to be 2.4
 and 4, respectively. Monte Carlo-simulations from these distributions showed that a total of
 200 patients, 100 in each arm, would yield a statistical power of 90% for Mann-Whitney U-test
 at a significance level of 0.05.

 In total, 200 consecutive patients with indication of are expected to be randomized in the
 study (100 patients in each arm, intramuscular vs subcutaneously). In Region Gavleborg , the
 annual primary implant volume of bradycardia pacemakers is approximately 220.

 Figure 1. Assumed distributions of patient overall satisfaction in the power analysis, as
 measured by an visual analogue scale where 0 means "very satisfied" and 10 means "very
 dissatisfied". The intramuscular group is assumed to follow a lognormal distribution with
 mean 1.5 and standard deviation of 1, on the logarithmic scale. The subcutaneous patients are
 assumed to follow a lognormal distribution with mean 1.5 and standard deviation of 1, on the
 logarithmic scale.

 Randomization: At the time of implant 1:1 randomization (100 patients in each group) to
 either subcutaneous (usual care) or intramuscular implant, in blocks with random block sizes.
 The randomization is performed by a statistician with no insight in the ongoing clinical work
 and patients' group allocation is revealed for implanting physician by the assistant nurse at
 the start of the surgical procedure. Randomization procedure: stratification (age strata: ≤65
 years and >65 years) and sex (female, male); totally 4 strata). Consecutive group allocations
 will be stored in sealed opaque envelopes that will be opened at the time of starting the
 implant procedure.

 Inclusion: Indication of a bradycardia pacemaker (DDDR, VVIR). Exclusion: Cardiac
 Resynchronisation Therapy Pacemaker (CRTP), Cardiac Resynchronisation Therapy Defibrillator
 (CRTD), implantable cardioverter defibrillator (ICD). Very skinny patient deemed as such by
 implanting physician to clearly benefit from intramuscular implant.

 Surgical procedure: Standard procedure and vascular access by each operator's preference.
 Blunt dissection of the pocket.

 Statistical methods: For comparisons between groups: Mann-Whitney U-test. For test of changes
 in VAS-estimations between 1, 12, and 24 months: pair-wise Wilcoxon signed-rank test.

 Informed consent: Written and oral information by nurse/physician before implant.

 Ethical approval: Approved by Uppsala Regional Committee. Clinical Trial Registration:
 Registration before start of study.

 Variables:

 Clinical variables: age, sex, coronary artery disease, open-heart surgery, diabetes, kidney
 disease Pacemaker system: (VVIR, DDDR), brand, model (lead(s) and device. Vascular access:
 (cephalic, axillary, subclavian vein), fluro-time, procedure time Periprocedural analgetics
 (dosage): alfentanil, morphine, diazepam, paracetamol Pre och post-operative anticoagulant
 medication (dosage and withdrawal with respect to procedure: acetylic acid, clopidogrel,
 ticagrelor, dual oral anticoagulants, warfarin, low-molecular weight heparin) Preoperative
 current medication: (psychoactive drugs, betablockers, corticosteroids, inflammatory
 modulating drugs Outcome measurements: Patient satisfaction (overall, chronic pain,
 discomfort, degree of unsightly look, movement disorder due to device, sleep problems due to
 device) scale 0-10 (10 worst) Paper questionnaire at 1,12,and 24 months. Patient knowledge if
 device was intramuscular or subcutaneously implanted at 24 months.

 Pacemaker nurse judgement: unsightly look (0-10, 10 worst). Physician evaluation (blinded to
 the patient and not operator in the study): photo of pocket (1, 12, 24 months) scale 0-10 (10
 worst).

 Complications requiring surgery: pocket revision, dislodgment, hematoma requiring surgery,
 infection (local, systemic), pneumothorax, pericardial effusion requiring drainage, other.

 Clinical perspectives: The surgical approach to the pacemaker pocket needs to be evaluated.
 The optimal approach including patient reported outcomes may result in more long-term
 satisfaction and may reduce the need for pocket revisions.
Inclusion Criteria:

 -  Indication of a bradycardia pacemaker (DDDR, VVIR).

 Exclusion Criteria:

 -  CRTP, CRTD, ICD.

 -  Very skinny patient deemed as such by implanting physician to clearly benefit from
 intramuscular implant.