The Safety and Efficacy of Disinfection Cap Use in a Real-World Environment

Abstract

Purpose

Catheter hub and needle-free connector contamination is a causative element in the development of catheter-related bloodstream infections and demonstrates the necessity for effective hub disinfection. The current study evaluated the safety and efficacy of a disinfection cap used in a real-world environment.

Patients and Methods

This multicenter, single-arm, prospective post-market study was designed to collect clinical data on the safety and performance of a passive disinfection cap. A total of 157 participants were included in this study. The primary performance endpoints were attachment and removal success rates. The primary safety endpoint was the rate of device-related AEs.

Results

A total of 156 participants, aged 3–93 years, had at least one disinfection cap applied during the study. Attachment and removal success was ≥ 99.7%. No device-related adverse events were observed.

Conclusion

This study found that disinfection caps can be attached and removed successfully with no device-related adverse events in a real-world environment.

Introduction

Catheter-related bloodstream infections (CRBSI) are bacterial infections that originate within a vascular access device (VAD) and have an estimated attributable mortality rate of up to 34%.1 Introduction of bacteria into the bloodstream via the VAD can come from several sources, including contamination of the device prior to insertion, skin organisms, contamination of the infusate, and contamination of the catheter hub.2 There are multiple recommendations for CRBSI prevention that target each of these potential origin points. For needleless connectors, the 2011 guidelines for the prevention of intravascular CRBSIs recommend scrubbing the access port of needleless connectors with an appropriate antiseptic, including 70% isopropyl alcohol (IPA).3 More recent guidelines and standards of clinical practice have included passive disinfection caps in their recommendations, with other guidelines suggesting that antiseptic-barrier caps for needle-free connectors (NFC) show favorable outcomes for decreasing the incidence of infection.4,5

Hub contamination is a causative element in CRBSIs and one that demonstrates the necessity for effective hub disinfection of NFCs prior to access.2 Disinfection of NFCs has been emphasized as an instrumental part of best practice recommendations in intravenous catheter care, and adoption and compliance to published guidelines on disinfection are of critical importance in promoting and maintaining patient safety.4,5 However, literature has identified low compliance to disinfection practices being a problem, especially given NFCs have been reported as the greatest risk of contamination following catheter insertion.6 Across a total of 140 studies, Moureau and Flynn reported proper disinfection compliance as low as 10%.6 Further, another article found that only 3.7% of nurses performed an adequate duration of scrubbing the hub for proper hub disinfection. Alcohol-impregnated disinfectant caps were developed to simplify the disinfection process through passive disinfection and to act as a physical barrier between line accesses.4,7 Aside from the added simplicity, passive disinfecting caps have been shown to be as effective as, and in some instances exceeding that of, active disinfection approaches (ie alcohol wipe disinfection, scrub cap disinfection) in reducing contamination and the incidence of central line associated bloodstream infection (CLABSI).8–11

The Infusion Nursing Society’s 2024 Infusion Therapy Standards for Practice states to disinfect “needleless connectors attached to VAD via disinfection caps or mechanical scrubbing with a pad or wipe containing 70% IPA or alcohol based chlorhexidine suitable for use with medical devices”.4 While the benefits of disinfecting caps have clearly been recognized, it is important to note that successful disinfection is inextricably linked to effective implementation of proper vascular care, maintenance strategies, and consistent adherence to recommended disinfection practices. The current study aimed to evaluate the safety and efficacy of disinfection caps in a real-world hospital setting.

Materials and Methods

This multicenter, single-arm, prospective, post-market study was designed to collect clinical data on the safety, performance, and use of the BD PureHub™ Disinfecting Cap (Becton Dickinson & Co., Franklin Lakes, New Jersey, USA). This disinfecting cap is designed to disinfect swabbable NFCs and to function as a physical barrier between line accesses for up to seven days with a sterilized 70% IPA solution in alignment with current guidelines and recommendations.3,4,12 This was a single-arm study with no control arm being used. In this study, disinfection caps were used as intended and as per the Instructions for Use for the product. The study was conducted between January 31st, 2021, and May 21st, 2023, with investigational sites spanning across Austria, Belgium, Italy, and Spain. The study was performed in accordance with the Declaration of Helsinki, Good Clinical Practice (GCP) ISO 14155:2020, and approved by an ethics committee at each investigational site. This clinical study was pre-registered on clinicaltrials.gov (NCT05130762).

Participants were screened against eligibility criteria and considered enrolled once the informed consent document was signed. Each study participant had a disinfection cap attached to each eligible NFC on one or more VADs by a clinician. Clinicians were advised to place subsequent disinfection caps as per the Instructions for Use throughout the course of the participant’s intravenous therapy. During this time, attachment and removal success were captured, as well as any device-related adverse events (AEs).

In order to be eligible to participate in this study, participants of any age or gender must have met all of the following criteria:

• Had an eligible VAD in situ or would have one placed with NFCs

• Was expected to receive VAD therapy for a minimum of 3 days

• Was expected to be available for regular observation from consent until end of study

• Was able and willing to provide informed consent or have a legal authorized representative to give consent on behalf of the participant.

Participants were excluded from the study if any of the following criteria applied:

• Any disinfecting cap in place for more than twelve hours (>12 hours) prior to study participation

• Presence of any infection, bacteremia, or septicemia was known or suspected

• Any condition which, in the opinion of the Investigator, precluded the participant from participation in the study.

Participants were followed from the time of enrollment until one week post VAD therapy, department/hospital discharge, or 45 days post enrollment date, whichever came first. Participants with a VAD in place, who were discharged from the hospital, but returned regularly to the site for catheter access remained in the study, either until the 45 days were reached or the VAD therapy ended. If the catheter access was not performed at the clinical trial site, the participant could not continue in the study. A participant could withdraw from the study at any time at his/her own request or may have been withdrawn at any time at the discretion of the Investigator or Sponsor for safety, behavioral, compliance, or administrative reasons. At the time of discontinuing from the study, no further data would have been collected from the participant.

Primary Performance Endpoints

The attachment success rate analysis was performed on the enrolled population of participants without missing data. If the clinician could successfully attach the first disinfection cap, it was considered as attachment success. The attachment success rate was calculated as the number of successful attachments divided by the total number of attachments. The removal success rate was calculated as the number of successful removals divided by the total number of removals.

Primary Safety Endpoint

The primary safety endpoint was the rate of device-related AEs. It was calculated as the number of participants with AEs related to the device divided by the total number of participants. In addition, bloodstream infections and CLABSI were assessed visually at four timepoints, during initial disinfection cap placement, each day during VAD therapy, at the 7-day follow-up after VAD therapy, and at the end of the study (45-day follow-up or at discharge, whichever occurred first). If there were any suspicion of a bloodstream infection, clinicians were instructed to follow their hospital policy for confirmation.

Safety Analysis

As per ISO 14155:2020 guidelines, an AE was defined as any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in participants, users, or other persons, whether or not related to the study device and whether anticipated or unanticipated. In this study, AE collection was limited to those events judged by the Investigator to be related or likely related to the disinfection cap and any events of bloodstream infection, including CLABSIs.

Statistics

Assuming the primary endpoints of successful insertion rate and successful removal rate are each 90%, a sample size of 150 participants with only one insertion/removal observed per participant would result in a 4.8% precision for each point estimate (ie, the 95% CI is the point estimate ±4.8%, using a simple asymptotic approach for CI of one proportion). The precision margin tightened as the number of line access per participant increased. For example, with an average of four insertions/removals per participant, the precision would be ±2.4%. Additionally, with a sample size of 150, the probability of observing at least one rare AE/complication with a 1% rate (per participant) was 78% and the probability of observing at least one rare AE/complication with a 2% rate (per participant) was 95%.

There was no hypothesis testing in this study. Unadjusted descriptive statistics were used such that summary statistics for categorical variables included frequency counts and percentages and for continuous variables included mean, standard deviation, minimum, median, and maximum. Clopper-Pearson confidence intervals were provided for the primary efficacy endpoint and the primary safety endpoint. All descriptive statistics were calculated using SAS software, version 9.4 (SAS Institute Inc., Cary, NC, USA). The quality of data collected at the study sites was assured by study monitoring procedures consistent with Good Clinical Practice guidelines.13

Results

Of the 157 enrolled participants, 156 had at least one disinfection cap applied and counted as evaluable participants. A total of 138 participants (88.5%) completed the study as per study protocol and 18 participants (11.5%) were discontinued. The main reasons for discontinuation were lost to follow up (n=12), physician’s decision (n=3), and withdrawal of informed consent (n=1). In addition, two participants died during the study. The two recorded deaths were unrelated to the study and were due to aggravation of pre-existing conditions.

The required number of participants were enrolled by a total of five sites across Europe, including Austria (n=30), Belgium (n=14), Italy (n=48), and Spain (n=65), over a period of 26 months. The participants’ ages ranged from 3 to 93 years with a mean age of 57.5 years. Participant demographics and baseline characteristics are shown in Table 1.

Table 1.

Demographic and Other Baseline Characteristics

	N=157
Age (year)*
Mean (SD)	57.5 (20.74)
Median	63.0
Min – Max	3–93
Sex
Male	80 (51.0%)
Female	77 (49.0%)
Race
Black or African American	2 (1.3%)
White	154 (98.1%)
White, Black or African American	1 (0.6%)

Note: *Age at signing informed consent.

Abbreviation: SD, Standard Deviation.

The most common primary diagnosis for admission at screening was oncological (51 participants [32.5%]), followed by neurological (37 participants [23.6%]), cardiac (four participants [2.5%]), vascular (three participants [1.9%]), trauma (two participants [1.3%]), and gastrointestinal (one participant [0.6%]). In 59 participants (37.6%) the primary diagnosis was categorized as “Other”. The most frequent primary diagnosis categorized as “Other” were neurosurgery, nasal septum deviation, metabolic, and respiratory.

During this study, several types of NFCs were used. It was possible that the initial used NFC was replaced with another model at a subsequent visit. The type and number of NFC’s used during the course of the study are reported in Table 2. The most frequently used NFC was ICU MicroClave™ with 129 (40.1%) applications, followed by BD MaxZero™ (46/322 [14.3%]) and ICU Clave™ (29/322 [9.0%]) devices. A total of 93 used NFCs (28.9%) were categorized as “Other”. Study monitors did not report any off-label use with the devices listed as “Other”.

Table 2.

Summary of NFCs Used

Type of NFC	NFCs N=322
ICU MicroClave	129/322 (40.1%)
BD MaxZero	46/322 (14.3%)
ICU Clave	29/322 (9.0%)
B.Braun CareSite	15/322 (4.7%)
BD Q-Syte	7/322 (2.2%)
BD NeutraClear	2/322 (0.6%)
Vygon Bionector	1/322 (0.3%)
Other	93/322 (28.9%)

Primary Performance Endpoints

Overall, disinfection cap attachment was successful in 99.9% of all participants. The initial attachment success rate and maintenance attachment success rates are shown in Table 3. Attachment success was not successful in one case as reported by the site due to “Infusion in elastomeric pump for 24 hours”. Due to the recorded therapy the attachment of the disinfection cap did not occur but was recorded as “not successful”. Overall, in 99.7% of all participants, the disinfection cap was removed successfully.

Table 3.

Primary Performance Endpoint

Endpoint	n (%)
Attachment success rate (N=1333)	1332 (99.9%)
Initial attachment success rate (N=294)	294 (100.0%)
Maintenance attachment success rate (N=1039)	1038 (99.9%)
Removal success rate (N=1095)	1092 (99.7%)

Primary Safety Endpoint

In this study, AE collection was limited to those events judged to be related or likely related to the disinfection cap, and any events of bloodstream infection, including CLABSIs. As shown in Table 4, no device-related AE or device deficiency occurred in any of the 157 participants. Throughout the course of the study, no participants with CLABSI or a bloodstream infection were observed across any timepoint of observation.

Table 4.

Primary Safety Endpoint

Endpoint	N = 157 (%)
Subjects with Device-related Adverse Events	0 (0.0%)
Participants with CLABSI	0 (0.0%)
Participants with Bloodstream Infection	0 (0.0%)
Serious Adverse Events	2 (1.3%)
Related to Device or Procedure	0 (0.0%)
Not Related to Device or Procedure	2 (1.3%)

Overall, only two AEs were reported in 2/157 (1.3%) participants in whom a disinfection cap was applied. Both AEs were reported as severe, with a fatal outcome. No AEs were considered related or likely related to the device or procedure. The first participant, a 72-year-old male participant, died due to aggravation of his oncological disease shortly after enrollment in the study. The second participant was a 77-year-old male who died due to respiratory insufficiency after a long chronic disease.

Discussion

This clinical study found that the disinfection cap, when used as intended, is safe, and can be applied and removed successfully in a real-world environment. The results of the current study revealed that clinicians successfully attached and removed disinfection caps in ≥99.7% of the applicable NFCs without any mechanical failure, malfunctions, or defects. Literature on the performance of disinfecting caps is sparse. In a review of literature to determine whether disinfection caps for NFCs can reduce the rate of bloodstream infection, Barton reported that the BD PureHub™ Disinfecting Cap has finger grips that ease application and removal and is brightly colored which aids health care professionals in following VAD care and maintenance.14 In addition, the review stated that the disinfecting cap can maintain a physical barrier for up to seven days if it is not removed during that time. The 2024 Infusion Therapy Standards of Practice and other guidelines recommend the use of disinfection caps.4,5,12 To our knowledge, this is the first study reporting on the efficacy of attachment and removal of passive disinfecting caps in a real-world environment.

This clinical trial also captured data related to the safety of disinfection caps when used in a real-world environment. No device-related or procedure-related AEs were observed, including zero cases of CLABSI or blood stream infections. Further, VAD location, medical device placement, dressing and securement, and the type of NFC attached to the disinfection cap did not lead to any device or procedure-related AEs. The results support that the disinfection caps are safe for use in a real-world environment. Literature investigating the use of disinfection caps has primarily focused on the impact of use in reducing infection.15 A single randomized clinical trial has reported the use of the disinfection cap used in this study in an investigation of skin disinfectant effectiveness.16 A total of 494 devices were included in the disinfecting cap group, which resulted in zero cases of CLABSI. A similar result was observed without the use of disinfecting caps with an incidence of zero cases of CLABSI. Further analysis of “additional trial components revealed that the use of closed integrated catheters, positive displacement needless-connectors, disinfecting caps and prefilled syringes extended the catheters complication-free dwell time”. The authors concluded that closed integrated catheters, positive displacement NFCs, disinfecting caps, and pre-filled flush syringes should be the rule when catheter dwell time is expected to exceed 24-hours.

To further evaluate the effectiveness of passive disinfection caps, two systematic reviews and meta-analysis compared manual disinfection with passive disinfection devices. One systematic review and meta-analysis identified 14 articles that compared manual disinfection and the use of antiseptic barrier caps in reducing CLABSIs.15 The authors found that antiseptic barrier caps significantly reduced CLABSI rate per 100 line-days and the number of CLABSI’s per patient. Through further subgroup analyses, it was revealed that antiseptic barrier caps were significantly more effective than manual disinfection in ICU patients, non-ICU patients, and in adult patients. The authors concluded that antiseptic barrier caps appeared effective in reducing CLABSI but that the real-world impact needs to be confirmed via randomized controlled trials. Another systematic review and meta-analysis found similar results when comparing antiseptic barrier caps and manual disinfection on the incidence of CLABSI.10 The meta-analysis of nine studies found that antiseptic barrier caps were effective in reducing CLABSIs. The authors concluded that antiseptic barrier caps were associated with a lower incidence of CLABSIs and that these barrier caps are “worth adding to central-line maintenance bundles”.

The benefits of using passive disinfection caps have also been observed when compared with active disinfection (ie, scrub caps, alcohol wipes, etc.)10,17 Flynn et al, conducted a meta-analysis on the effectiveness of decontamination when comparing disinfection wipes (active decontamination) and alcohol impregnated caps (passive decontamination).17 The authors found that IPA-impregnated caps were associated with less than one-half the risk of catheter-associated bloodstream infection when compared with 70% IPA wipes. Similarly, another meta-analysis reported that IPA-impregnated caps were associated with significantly less CLABSI when compared with IPA wipes.10 Additional studies have identified the benefits of reduced rates of contamination and infection when using antiseptic barrier cap and alcohol impregnated caps.9,18 The findings of the current study support the low incidence of CLABSI reported across several meta-analyses following use of disinfection caps, as no cases of CLABSI were observed in this study. However, the descriptive results reported herein are not causal in nature. Thus, future randomized trials should evaluate the effectiveness of disinfections caps and their impact on CLABSI.

Limitations of our study include a small sample size and the use of a single study arm without a comparator, which limits any assessment of the impact of disinfection caps on CLABSI rates relative to standard care. Another potential limitation was selection bias. Given the inclusion criteria only included patients requiring VAD therapy for ≥3 days, there may have been unintended selection bias towards more stable patients which limits generalizability of the results. We also acknowledge within-subject correlation was not accounted for in the descriptive analysis. In addition, the subjectivity in assessment of AEs was another limitation as this was determined by the investigator. Another potential limitation was the use of an “other” category that was selected for what NFC devices were connected to the disinfection cap to confirm proper use of the device. Given a study observer/coordinator was present to document any potential off-label use, it was determined that no off-label use was performed with the device.

Conclusion

This study found that disinfection caps can be successfully attached and removed with no device-related adverse events in a real-world environment. These findings support usability and safety; however, randomized controlled studies are required to determine their effectiveness in reducing bloodstream infections.

Funding Statement

This study was funded by Becton, Dickinson and Company (BD), Franklin Lakes, NJ, USA.

Abbreviations

CRBSI, catheter related bloodstream infection; VAD, vascular access device; IPA, isopropyl alcohol; NFC, needlefree connector; CLABSI, catheter line associated bloodstream infection; GCP, good clinical practice; AE, adverse event.

Data Sharing Statement

The datasets generated during the current study are available from the corresponding author on reasonable request. Results of the data generated during the current study are posted online at: https://www.clinicaltrials.gov/study/NCT05130762?term=PureHub&rank=1.

Ethical Considerations

The study was conducted in accordance with the Declaration of Helsinki and was approved by five Ethics Committees: Ethics Committee Area Vasta Centro Ufficio di Segreteria del Comitato Etico, Comité Ético de Investigación Clínica, CEIm Autonómico de Galicia, Ethikkommission der Medizinischen Universität Wien, and the Ethisch Comité UZA.

Consent to Participate

Written informed consent was required to participate in this study.

Author Contributions

TJS, JS, and KDB prepared the manuscript. TJS, JS, and KDB interpreted the data. All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

LSD, BD, MW, SM, and MEGL report payment for the clinical trial from Becton, Dickinson and Company (BD) to their institutions. KDB, TJS, and JS are employees of BD. KDB and JS own stock in BD. The authors report no other conflicts of interest in this work.