Placement Of Cardiac PacemaKEr Trial (POCKET) – rationale and design: a randomized controlled trial
Heart Int 2017; 12(1): e8 - e11
Article Type: CLINICAL TRIAL PROTOCOL
AuthorsPeter Magnusson, Leo Wennström, Robert Kastberg, Per Liv
A pacemaker system consists of one or two leads connected to a device that is implanted into a pocket formed just below the collarbone. This pocket is typically subcutaneous, that is, located just above the pectoral fascia. Even though the size of pacemakers has decreased markedly, complications due to superficial implants do occur. An alternative technique would be intramuscular placement of the pacemaker device, but there are no randomized controlled trials (RCTs) to support this approach, which is the rationale for the Placement Of Cardiac PacemaKEr Trial (POCKET). The aim is to study if intramuscular is superior to subcutaneous placement of a pacemaker pocket.
In October 2016, we started to enroll 200 consecutive patients with an indication for bradycardia pacemaker implantation. Patients are randomized to random block sizes, stratified by age group (cut-off: 65 years) and sex, and then randomized to either subcutaneous or intramuscular implant. A concealed allocation procedure is employed, using sequentially numbered, sealed envelopes. Pocket site is blinded to the patient and in all subsequent care. The primary endpoint is patient overall satisfaction with the pocket location at 24 months as measured using a visual analog scale (VAS) 0-10. Secondary endpoints are: complications, patient-reported satisfaction at 1, 12, and 24 months (overall satisfaction, pain, discomfort, degree of unsightly appearance, movement problems, and sleep problems due to device).
POCKET is a prospective interventional RCT designed to evaluate if intramuscular is superior to subcutaneous placement of a bradycardia pacemaker during a two-year follow-up.
- • Accepted on 27/02/2017
- • Available online on 13/04/2017
- • Published online on 14/04/2017
This article is available as full text PDF.
Implantation of a cardiac pacemaker may be indicated in patients with a second- or third-degree atrioventricular block, significant sinus node dysfunction, tachycardia-bradycardia syndrome, bundle branch block with syncope, and in certain disease states, according to current guidelines (1). Annually, around 691 pacemakers per million inhabitants are implanted in Sweden (2). In the 16 Western European countries, there was a steady increase in implants from 2005, which plateaued in 2009 with 928 units implanted per million inhabitants. The rate of implanted units range from 607 per million in Ireland to 1291 per million in Germany, with an average of 938 throughout Western Europe in 2011 (1).
A bradycardia pacemaker system consists of one or two leads connected to a device that is implanted below the collarbone (3, 4). Vessel access is typically gained on the left side through the cephalic, axillary, or subclavian vein. The pacemaker device is typically inserted into a pocket just above the pectoral fascia (subcutaneously). In very thin patients with little subcutaneous fat, an intramuscular pocket between the pectoral muscular layers may be used. Even though technological advances have decreased the size of pacemakers markedly over time, complications due to superficial implants do still occur (5, 6). Occasionally, the device erodes through the skin, necessitating complete extraction of the system (7). More frequently, patients may complain about the device being too prominent, which sometimes requires surgical repositioning (5, 6). The device may create discomfort, pain, and an unsightly appearance (5, 6). The lateral corner of the device may impede shoulder movement or impair sleep; leads can become tangled or wound up within the pocket (Twiddler’s syndrome). Minor branches of the supraclavicular nerves may become damaged, resulting in pain or discomfort. When vessels from the subcutaneous adipose tissue are displaced or distorted, extensive and painful hematomas may result. The development of a large hematoma is a known risk for infection (8, 9). In some cases, perfusion in the area of the operation may decrease and the amount of fat covering the device may be reduced to an unanticipated extent. The change-out of a device due to battery depletion can remove even more surrounding tissue. An alternative approach is an intramuscular placement of the device (10, 11). 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 our knowledge, no randomized controlled trial has ever addressed the question about the optimal placement of a bradycardia pacemaker.
Therefore, this paper presents the rationale and design of POCKET (
Consecutive patients with an indication for a bradycardia pacemaker have been included starting in October 2016 in Region Gävleborg, Sweden. All implants are performed at Kardiologiskt Interventionscentrum in Gävle with an annual volume of 460 device procedures. Four experienced operators, all cardiologists, enroll patients into the study and perform the implants.
Inclusion and exclusion
Patients, aged ≥18 years, with an indication for a bradycardia pacemaker (DDDR or VVIR) are eligible for the study. Inclusion is restricted to
Ethics and registration
The Regional Ethical Committee in Uppsala approved the study (protocol number 2016/371), which is conducted in compliance with the Declaration of Helsinki (12).
In order to declare the study protocol, including variables and pre-specified research questions, the study was registered at Clinical Trial Registration NCT02931760 and approved 11th of October 2016. Members of the research team all follow Guideline for Good Clinical Practice (13). Each patient is informed about the study in both oral and written form by the study physician and included after written consent.
The implantation procedure and vascular access are performed based on the preference of each operator. The pocket is created by blunt dissection and requires adequate local anesthesia. Typically, the patient is administered diazepam 5 mg preoperatively and then given local infiltrative anesthetics. Following surgery, paracetamol (acetaminophen) is recommended to control pain. The choice of pacemaker and lead(s) is made preoperatively before the patient’s group allocation is revealed. The pacemaker systems available are either the Assurity™ pacemaker and Tenril™/Tendril MRI™ leads (St. Jude Medical, St. Paul, MN) or Proponent EL MRI™ and Ingevity MRI™ leads (Boston Scientific, Marlborough, MA).
Randomization of the group allocation sequence was performed in permutated blocks with random block sizes, using stratification based on age (≤65 years and >65 years) and sex (female, male), creating four strata. Consecutive group allocations are stored in sealed opaque envelopes. The randomization was performed by a statistician with no involvement in the clinical work; patients’ group allocations are revealed to the implanting physician by the assistant nurse at the start of the surgical procedure.
A power analysis based on expectations and clinical experience of the research group was performed.
Assumed distributions of patient overall satisfaction in the power analysis, as measured by a visual analogue scale (VAS) 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.
In total, 200 consecutive patients with a bradycardia pacemaker indication are expected to be randomized in the study (100 patients in each arm, intramuscular vs. subcutaneous). In Region Gävleborg, the annual primary implant volume of bradycardia pacemakers is approximately 200.
Frequencies, percentages, means, and percentiles describe numeric data. Continuous variables are summarized as means, standard deviations (SDs), and percentiles, and compared using t-tests; the chi-squared test is used for categorical variables. The Mann-Whitney U-test will be used for group comparisons of the VAS-scale results. For the test of changes in VAS estimations between 1, 12, and 24 months, pair-wise Wilcoxon signed-rank test is used.
A two-sided p value of <0.05 is considered statistically significant. The database in Excel 2010 (Microsoft Corporation, Redmond, WA) will import into SPSS version 22 (IBM, Armonk, NY).
Patient characteristics at enrollment, periprocedural variables and outcome variables at follow-up are presented in
Variables with regard to clinical characteristics, medication before and during implant, and surgical procedure
|SD = standard deviation.|
|Age, mean (SD)|
|Male sex (yes/no)|
|Coronary artery disease (yes/no)|
|Previous open heart surgery (no/yes)|
|Diabetes (0 = no, 1 = yes, insulin, 2 = yes, oral medication)|
|Kidney disease (yes/no)|
|Smoking history (current/ex-smoker/never smoker)|
|Medication before implant|
|Acetylsalicylic acid (yes/no)|
|Novel oral anticoagulant (yes/no)|
|Low-molecular weight heparin (yes/no)|
|Paracetamol (acetaminophen) (yes/no)|
|Nonsteroidal anti-inflammatory drugs (yes/no)|
|Selective serotonin reuptake inhibitors (yes/no)|
|Sleeping pills (yes/no)|
|Other psychoactive drugs (yes/no)|
|Immunomodulation drugs (other than steroids) (yes/no)|
|Paracetamol (acetaminophen) (0 = no, 1 = yes, dosage)|
|Opioid (0 = no, 1 = yes, dosage)|
|Diazepam (0 = no, 1 = yes, dosage)|
|Alfentanil (0 = no, 1 = yes, dosage)|
|Other analgesic (specify) (0 = no, 1 = yes, dosage)|
|Vascular access (subclavian/axillaris/cephalic)|
|Fluoroscopy time (min)|
|Device lead (atrium) brand/name|
|Device lead (ventricle) brand/name|
|Indication (sick sinus syndrome/atrioventricular-block/atrial fibrillation with tachycardia/bradycardia or solely bradycardia/other)|
Outcome and follow-up
Patients will be evaluated by a pacemaker nurse specialist at 1, 12, and 24 months. During these three clinical visits, a questionnaire will be distributed (see supplementary material available online at www.heart-int.com). The questionnaire asks patients to estimate their satisfaction with the device on a VAS scale (0-10) considering the following aspects: overall satisfaction, chronic pain, discomfort, degree of unsightly appearance, limited movement due to device, and sleep problems due to device. At 24 months, patients are asked to guess if the device was implanted in an intramuscular or subcutaneous pocket in order to validate the overall degree of patient blinding. The pacemaker nurse’s evaluation of the unsightly appearance of the pocket (0-10, 10 worst) is blinded to the patient.
Certain complications might necessitate another surgery: pocket revision, lead dislodgment, hematoma requiring surgery, infection (local, systemic), pneumothorax, pericardial effusion requiring drainage, and other.
We developed a questionnaire to assess the patients’ pacemaker experience with a special emphasis on the pocket. The pacemaker-related questions were based on input from expert discussions with cardiologists and pacemaker-nurses experienced in the follow-up of pacemaker patients. The questionnaire was tested on lay people for language clarity and layout. It was decided to use a paper-version for the convenience of the patients evaluated. The questionnaire can be downloaded as supplementary material from www.heart-int.com.
Implantation of a permanent pacemaker is a common procedure and represents lifelong therapy. This implies that potentially chronic problems need to be considered in addition to procedural complications. The pacemaker device has undergone remarkable technological advancements and its weight and footprint have decreased drastically. Those relatively rare device recalls notwithstanding, most pacemakers provide reliable pacing support for a decade or more before the device needs to be replaced (14). Since many pacemaker patients are geriatric with comorbid conditions at implant, they may die before the device requires replacement (15). In those instances when long-term pacemaker failure occurs, it is often related to lead problems (typically involving either the wire or the insulation), and there can be tissue damage at the lead interface (16). Although national pacemaker registries report technical data about device system and complications, actual complication rates may be under-reported (5). Complications necessitating surgical intervention can be perceived as problematic by the patient, although they can usually be handled without long-term effects. Clearly, device-pocket-related problems may be troublesome for longer periods of time, which may affect patients both physically and emotionally. While pacemakers are usually inserted subcutaneously, intramuscular placement may offer advantages. To handle confounding factors, the RCT is an ideal design to address the question as to whether one approach is superior to the other with respect to different outcome measurements, including possible predictors thereof (17, 18).
Taking into account the potential global burden of pacemaker-related problems, the surgical approach to the pacemaker pocket needs to be evaluated. A better understanding of the optimal approach (subcutaneous vs. intramuscular) and its relationship to outcomes may result in improved long-term satisfaction with pacemaker therapy and might reduce the need for pocket revisions.
Strengths and weaknesses
This prospective RCT will elucidate whether an intramuscular or subcutaneous pacemaker pocket is preferred by patients and how its appearance is visually judged by a healthcare provider. The sample size has the power to answer the research question about overall satisfaction over the course of a two-year follow-up period. The two-year study duration does preclude explant due to elective replacement and very long follow-up periods.
POCKET is a prospective interventional RCT designed to evaluate if intramuscular pocket placement of a bradycardia pacemaker is superior to subcutaneous placement over a two-year follow-up.
Brignole M Auricchio A Baron-Esquivias G et al. European Society of Cardiology (ESC); European Heart Rhythm Association (EHRA). 2013 15 8 1070 1118
Gadler F Valzania C Linde C Current use of implantable electrical devices in Sweden: data from the Swedish pacemaker and implantable cardioverter-defibrillator registry. 2015 17 1 69 77
Rajappan K Permanent pacemaker implantation technique: part I: arrhythmias. 2009 95 3 259 264
Rajappan K Permanent pacemaker implantation technique: part II. 2009 95 4 334 342
Kirkfeldt RE Johansen JB Nohr EA Jørgensen OD Nielsen JC Complications after cardiac implantable electronic device implantations: an analysis of a complete, nationwide cohort in Denmark. 2014 35 18 1186 1194
Kistler PM Fynn SP Mond HG Eizenberg N The subpectoral pacemaker implant: it isnt what it seems! Pacing Clin Electrophysiol. 2004 27 3 361 364
Buch E Boyle NG Belott PH Pacemaker and defibrillator lead extraction. 2011 123 11 e378 e380
Essebag V Verma A Healey JS et al. BRUISE CONTROL Investigators. 2016 67 11 1300 1308
Johansen JB Jørgensen OD Møller M Arnsbo P Mortensen PT Nielsen JC Infection after pacemaker implantation: infection rates and risk factors associated with infection in a population-based cohort study of 46299 consecutive patients. 2011 32 8 991 998
Gold MR Peters RW Johnson JW Shorofsky SR Worldwide Jewel Investigators. 1996 28 5 1278 1282
Gold MR Peters RW Johnson JW Shorofsky SR World-Wide Jewel Investigators. 1997 20 1 Pt 2 208 211
World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. 2002 48 3 206 208
European Medicines Agency. Available from http://www.edctp.org/fileadmin/documents/EMEA_ICH-GCP_Guidelines_July_2002.pdf.Accessed March 31, 2017.
Maisel WH Pacemaker and ICD generator reliability: meta-analysis of device registries. 2006 295 16 1929 1934
Greenspon AJ Patel JD Lau E et al. Trends in permanent pacemaker implantation in the United States from 1993 to 2009: increasing complexity of patients and procedures. 2012 60 16 1540 1545
Kirkfeldt RE Johansen JB Nohr EA Moller M Arnsbo P Nielsen JC Risk factors for lead complications in cardiac pacing: a population-based cohort study of 28,860 Danish patients. 2011 8 10 1622 1628
Devereaux PJ Yusuf S The evolution of the randomized controlled trial and its role in evidence-based decision making. 2003 254 2 105 113
La Caze A Why randomized interventional studies. 2013 38 4 352 368
- Magnusson, Peter [PubMed] [Google Scholar] 1, 2, * Corresponding Author (firstname.lastname@example.org)
- Wennström, Leo [PubMed] [Google Scholar] 2
- Kastberg, Robert [PubMed] [Google Scholar] 2
- Liv, Per [PubMed] [Google Scholar] 2
Cardiology Research Unit, Department of Medicine, Karolinska Institutet, Stockholm - Sweden
Centre for Research and Development, Uppsala University/Region Gävleborg, Gävle - Sweden
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