Clinical benefit of adding cyanoacrylate glue during PICC line insertion compared to standard procedure in outpatient cancer patients: Results from the randomized prospective trial PICCandGLUE

Abstract

Background:

Peripherally inserted central catheters (PICCs) can be used to administer a variety of intravenous therapies to cancer patients. PICC insertion can be associated with bleeding at the puncture site requiring additional care and dressing repairs. Several studies suggest that the addition of cyanoacrylate glue (CAG) at PICC insertion reduces the risk of bleeding and the further need for compresses, as well as catheter-related complications.

Methods:

This monocenter, randomized, controlled, prospective study was conducted in the vascular access unit (VAU) of the French comprehensive cancer center Léon Bérard. The primary objective was to compare the efficacy of PICC insertion with CAG versus without glue in cancer patients requiring central venous access. Success was defined as the absence of compress requirement at the end of the procedure. Secondary objectives included the number of patients needing a change of dressing within 1 h, at day 8 and at day 30, and the incidence of PICC removal and PICC-related complications in the 30 days following insertion.

Results:

From August 2023 to July 2024, 98 outpatients were randomized (1:1) in the experimental arm (CAG, n = 48) or in the standard arm (without glue, n = 50). Success occurred in 47 (98%) patients in the CAG arm versus 39 (78%) in the standard arm (p = 0.001). Within the first hour 1 (2%) patient in the CAG arm required a change of dressing compared to 23 (46%) in the standard arm (p < 0.001). During the 30-day follow-up period, no significant differences between the two arms in terms of change of dressing or complications were reported.

Conclusion:

CAG provides an immediate benefit at the end of PICC insertion that lasts for up to 1 h after the end of the procedure. The use of CAG would improve the organization of the catheter placement unit and reduce the need for post-procedure nursing care.

Keywords

Peripherally inserted central catheter dressing tissue adhesive vascular access unit nursing cyanoacrylate glue

Introduction

Vascular access devices are regularly placed to deliver treatments to cancer patients, such as systemic anticancer therapies, parenteral or long-term intravenous therapies, supportive care treatments, or blood samplings. Peripherally inserted central catheters (PICC) are one type of vascular access device that is percutaneously inserted into a vein, usually in the arm, with the distal end located at the cavo-atrial junction. The use is usually for therapy that needs to be administered weekly.¹

To insert a PICC, the skin and subcutaneous tissues must be punctured and the catheter secured with an adhesive sutureless device (e.g. Statlock type). A sterile transparent semipermeable membrane (TSM) dressing should cover the PICC exit site, and has to be changed at least every 8 days.²

Tissue puncture results in bleeding at the puncture site in 25%–40% of the procedures.^3,4 In case of bleeding, a sterile compress is applied before being covered with the transparent dressing.² If the compress gets wet with blood, it should be changed before patient hospital discharge. Moreover, the dressing of the skin puncture point covered by a compress must be changed the day after the procedure, either at hospital or at home (home nurse or nurse office).² Therefore, in case of bleeding, additional cares are needed.

Cyanoacrylate glues are sterile adhesives composed of cyanoacrylates for cutaneous local application. These glues are particularly indicated for closing cuts or lacerations, as well as punctures and small surgical incisions, particularly at catheter insertion sites, thanks to their ability to easily adapt to wound edges.⁵

Recent findings from Padilla-Nula et al. showed a reduced risk of peri-catheter bleeding and/or oozing during the 7-day study period when using the cyanoacrylate glue during PICC insertion in hospitalized patients.⁶ No evaluation was conducted soon after insertion (2 h) in the Padilla-Nula study.⁶ Other available clinical data suggest immediate and prolonged efficacy of cyanoacrylate glue in preventing puncture-site bleeding but results remain unconclusive due to limitations in the studies designs.^3,4,7 For outpatient PICC insertion, no study has evaluated the immediate or prolonged benefit of glue at PICC insertion.

We investigated cyanoacrylate glue efficacy in reducing the risk of bleeding during outpatient PICC insertion. Less compress requirement would result in organizational relief with reduced dressing changes and may lower the risk of catheter-related infections.

Methods

Study design and objectives

The randomized, controlled, comparative, prospective study PICCandGLUE (NCT05944900) was carried out in the Vascular Access Unit (VAU) of the French Comprehensive Cancer Center Léon Bérard. The study was conducted in accordance with the regulations in force and received regulatory approval from an ethics committee on June 28th 2023.

The primary objective was to compare the efficacy of PICC catheter insertion using cyanoacrylate glue versus without glue in cancer patients requiring central venous chemotherapy or immunotherapy. The primary endpoint was the success rate of the procedure, with success being defined as the application of a transparent dressing without the need for a compress at the end of insertion (i.e. with no bleeding observed after the defined compression time). A dressing change was performed in the event of active bleeding from the puncture site threatening the integrity of the dressing.

Secondary objectives were: the proportion of patients who required a change of dressing within 1 h after the end of the procedure, at day 8 and at day 30; the incidence of PICC removal and PICC-related complications (requiring or not PICC replacement) in the 30 days following insertion.

In addition, a cost analysis of the additional use of cyanoacrylate glue and its impact in terms of organization (flow model and a discrete-event simulation model) was conducted and will be described in another article.

Study population

Patients scheduled for a PICC insertion in the VAU were included in the trial, provided that they were eligible and that one of the study investigators was present in the VAU. Patients were considered eligible if they fulfilled all the following criteria: ⩾18 years old, histological diagnosis of cancer, indication of chemotherapy or immunotherapy intended to be administered through a single lumen PICC inserted on an outpatient basis in a superior limb, with a duration of use planned to be >30 days.

Patients who already participated in the study, with known allergies to cyanoacrylates, to D&C violet and formaldehydes, unable to be contacted by phone, under tutorship or curatorship or who did not speak French were not eligible.

All patients gave a written informed consent prior to being enrolled in the study.

Study procedures

Using an on-line randomization platform, eligible patients were randomly allocated in a 1:1 ratio by the VAU team to have a PICC insertion either according to standard procedure (standard arm) or with the additional use of a cyanoacrylate glue (experimental arm). Randomization was stratified by the risk of hemostasis disorders: at least one risk factor (concomitant treatment interfering with hemostasis, innate and/or acquired coagulation troubles, thrombopenia) or absence of risk factor.

In both arms, procedures of PICC line insertion complied with the guidelines of the SIP2 Protocol, using the Statlock system.⁸ Factors that may influence bleeding were standardized: shortest possible tourniquet placement time (released as soon as the peelable introducer is placed in the vein), short skin puncture (max. 3 mm) at the guidewire entry point, manual compression at the catheter exit point using a dry compress for 60 s (If bleeding persisted beyond 1 min, a compress was left in place at the puncture site.), catheter not protruding beyond marker 2 (reverse-tip catheters (powerpicc solo2^®) wider over the first 4 cm). Chlorexhidine 2% was used, followed by a transparent semi-permeable dressing without integrated antiseptic, with gauze in case of bleeding. The glue used in our study was removed after the first dressing, when the antiseptic was rubbed in. There was no subsequent reapplication of glue.

The cyanoacrylate glue used in this study was Leukosan Adhesive (Essity), now marketed under the name Leukoplast skin adhesive, composed of 2-octyl cyanoacrylate (approximately 58%) combined with n-butyl cyanoacrylate (approximately 34%). Essity provided the cyanoacrylate glue free of charge for all patients randomized in the experimental arm.

Data management and collection

At inclusion and at the day of procedure (D0), study data were collected from the patients’ medical files and a study-specific form was filled-in during the procedure to collect additional information. A diary was given to the patients so that they could indicate any intervention on the dressing and any complication during their follow-up. Patients were followed-up during 30 days after the PICC insertion, with a phone call on day 1 (D1; for patients who did not return to our cancer care center on D1), day 8 (D8), and day 30 (D30) after the procedure. Data base was locked on October 1st 2024. The study database was developed and maintained in compliance with applicable study regulations using ENNOV Clinical software.

Statistical methods

Considering a success rate of 75% in the standard arm and 95% in the experimental arm, according to current scientific evidences, 98 patients (49 per arm) were needed to show a significant difference between arms using a χ² test with a 80% power and a two-sided 5% alpha level.⁹

Patients’ characteristics and results of the primary and secondary endpoints are presented in the Intent-To-Treat (ITT) population that is, all the randomized patients. Safety analysis were performed on patients who had a PICC insertion and were followed at least 1 h after the procedure.

Qualitative data are presented with frequencies and percentage (n, %), and quantitative data with median and range (min–max).

Comparisons between the two arms were performed using χ² test or Fisher’s Exact test for qualitative data and with Student or Wilcoxon’s tests for quantitative data. All comparisons were done with a 5% bilateral alpha level.

Data analysis was performed using SAS^® v9.4 software.

Results

Patients

From August 2nd 2023 to July 19th 2024, 98 patients were randomized in the experimental arm (n = 48) or in the standard arm (n = 50). All included patients had a diagnosis of solid tumor. PICC line insertion procedure failed for one patient in each arm (not related to the study procedures), who received a tunneled catheter which we reported and considered in the statistical analysis, as the choice of tunneling was made after randomization. The other catheters were non-tunneled to the extent that we were able to obtain the catheter emergence zone in the ZIM green zone (Figure 1 and Table 1).

Figure 1.

Study flow chart.

Table 1.

Patient and treatment characteristics at baseline.

Criteria	Experimental (n = 48)	Control (n = 50)	Total (n = 98)	p
Age (years)	58 (27–87)	60 (20–81)	59 (20–87)	0.95
Male	14 (29)	25 (50)	39 (40)	0.04
Hemostasis risk	3 (6)	5 (10)	8 (8)	0.71
Thrombo-embolism history	1 (2)	1 (2)	2 (2)	1.00
Central catheterization history	8 (17)	12 (24)	20 (20)	0.45
Cancer treatment strategy
Neoadjuvant	20 (42)	17 (34)	37 (38)	0.75
Adjuvant	24 (50)	28 (56)	52 (53)
Metastatic	4 (8)	5 (10)	9 (9)
Anticancer treatment indicated^a
Chemotherapy	48 (100)	50 (100)	98 (100)	—
Immunotherapy	0 (0)	1 (2)	1 (1)

p: p-value from the comparison between the two arms (Fisher exact or Wilcoxon test, as appropriate).

Data are given as absolute numbers n (%), and median (min-max) for each group, as appropriate.

Anticancer treatment could be used in combination with (total >100%).

The median age of the population was 59 (20–87) years. Eight (8%) patients had a risk factor for hemostasis disorders. Before their inclusion, 2 (2%) patients had a history of thrombo-embolism and 20 (20%) of central catheter insertion, including 13 (13%) by PICC. Except for the sex ratio (n = 59, 60% females), baseline characteristics, including the risk of hemostasis disorder, were well-balanced between groups (Table 1).

Efficacy and safety at day 0

The primary objective was met with 47/48 (98%) patients in the experimental arm that did not require a compress at the end of the procedure (no bleeding) compared to 39/50 (78%) patients in the standard arm (p = 0.001). Two patients did not achieve a complete PICC placement, one in the experimental arm and one in the standard arm, and were considered as failures. A sensitivity analysis was conducted, considering the patient in the experimental arm as a failure, and the one in the standard arm as a success. It confirmed the results of the primary endpoint analysis (p = 0.008; Table 2).

Table 2.

Procedure evaluation at day 0.

Criteria	Experimental (n = 48)	Control (n = 50)	Total (n = 98)	p
Primary endpoint (ITT) success	47 (98)	39 (78)	86 (88)	0.001
Dressing change within the first hour	1 (2)	23 (46)	24 (24)	<0.001
Complications to PICC insertion	1 (2)	3 (6)	4 (4)	0.62
Duration in the operating room (min)	28 (14–50)	26 (16–77)	27 (14–77)	0.54

p: p-value from the comparison between the two arms (Fisher exact or Wilcoxon test, as appropriate).

Data are given as absolute numbers n (%), and median [min-max] for each group, as appropriate.

Dressing change within the first hour after the procedure was significantly less needed in the experimental arm (n = 1, 2%) than in the standard arm (n = 23, 46%; p < 0.001). The occurrence of PICC-related immediate complications was not significantly different between the two groups (n = 1, 2% in experimental arm vs n = 3, 6% in standard arm, p = 0.62). The median procedure time, defined as the time from entry to exit from the operating room, was similar between the two arms: experimental arm: 28 (14–50) min; standard arm: 26 (16–77) min; p = 0.54 (Table 2).

Thirty days follow-up of dressing changes and safety

During the 30-day follow-up period, the median number of interventions per patient was 7 (1–23) in the experimental arm and 6 (2–19) in the standard arm (p = 0.81). The dressings were changed in median 5 times in each group (p = 0.41). The majority of patients required a change of dressing (experimental arm n = 34, 71%; standard arm n = 37, 74%). One PICC (2%) in the experimental arm and 3 (6%) in the standard arm were removed (p = 0.62). No difference was observed in the median number of cancer treatments between the two groups: 3 (1–13) in the experimental arm versus 4 (1–13) in the standard arm, p = 0.28 (Tables 3 and 4).

Table 3.

Procedure follow-up from day 0 to day 30 after PICC insertion.

Criteria	Experimental (n = 48)	Control (n = 50)	Total (n = 98)	p
From day 0 to day 8 after PICC insertion
Intervention on PICC dressing	2 (1–8)	2 (1–6)	2 (1–8)	0.93
Dressing change	1 (1–3)	1 (1–3)	1 (1–3)	0.76
PICC withdraw	0 (0)	1 (2)	1 (1)	1.00
Cancer therapy infusion	1 (1–6)	2 (1–6)	1.5 (1–6)	0.33
Other interventions	5 (1–6)	1 (1–5)	1 (1–6)	0.14
From day 0 to day 30 after PICC insertion
Intervention on PICC dressing	7 (1–23)	6 (2–19)	7 (1–23)	0.81
Dressing change	5 (1–6)	5 (1–7)	5 (1–7)	0.41
PICC withdraw	1 (2)	3 (6)	4 (4)	0.62
Cancer therapy infusion	3 (1–13)	4 (1–13)	3 (1–13)	0.28
Other interventions	4 (1–17)	1 (1–8)	3.5 (1–17)	0.58

p: p-value from the comparison between the two arms (Fisher exact or Wilcoxon test, as appropriate).

Data are given as absolute numbers n (%), and median [min-max] for each group, as appropriate

Table 4.

Complications follow-up from day 0 to day 30.

Criteria	Experimental (n = 48)	Control (n = 50)	Total (n = 98)	p
Overall complications	7 (15)	7 (14)	14 (14)	1.0
Infection	1 (2)	0 (0)	1 (1)	1.0
Thrombosis	1 (2)	2 (4)	3 (3)	1.0
Displacement	4 (8)	2 (4)	6 (6)	0.59
Other	1 (2)	3 (6)	4 (4)	0.56

p: p-value from the comparison between the two arms (Fisher exact or Wilcoxon test, as appropriate).

Data are given as absolute numbers n (%).

Seven patients in each arm (n = 14, 14%) experienced the following PICC-related complications: PICC displacement (n = 6, 6%), infection (n = 1, 1%), thrombosis (n = 3, 3%), medical adhesive related skin injury (n = 1, 1%), bleeding (n = 1, 1%), lymphatic drainage (n = 1, 1%). No significant differences between the two arms were reported (Table 4).

Discussion

The addition of cyanoacrylate glue during PICC insertion prevented bleeding and consequently the need for compresses, translating into an improved efficacy compared to standard procedure. Significantly less changes of dressing were required within the first hour after the procedure and no additional complications were reported. No difference in terms of efficacy and safety during the 30 days follow-up were observed between the two conditions.

Our results are consistent with recent findings from Padilla-Nula et al. assessing the efficacy of cyanoacrylate glue to secure catheters in hospitalized patients. This randomized controlled trial reported that adding cyanoacrylate glue reduces bleeding and oozing (n = 38, 37%) compared to standard procedure (n = 56, 51%; p = 0.04).⁶ Several retrospective or pilot studies showed that the addition of glue during PICC placement results in bleeding rates ranging from 0% to 43%. However, these trials were not designed to compare the efficacy of the glue or at least not in terms of bleeding.^9
–12 In addition, results of studies conducted in pediatrics settings cannot be fully transposed to adults.¹³ Despite these limitations, their conclusions suggest that a PICC placement strategy including a glue reduces bleeding at the puncture site.

The results of the current study are slightly above the predefined statistical assumptions in both arms (75% and 95% in both arms in predefined assumptions vs 78% and 98% in both arms in current study). This can be explained by the experience of the vascular access unit team (in our vascular access unit, over 3000 central catheters are placed every year) and by standardized PICC placement procedures (including compression).

Regardless of team experience, any per-procedure issue significantly impacts the unit organization. In particular, patients who experience bleeding at the end of the procedure need a sterile compress that must be changed the day after the PICC insertion by a homecare nurse. As cyanoacrylate glue prevented the bleeding with no additional time spent by the patients in the operating room, it may improve the unit organization. It may also reduce the need for additional nurse care, as the proportion of patients requiring a dressing change within an hour of PICC insertion fell sharply (2% with glue vs 46% without).

Considering that the risk of infectious colonization is associated with dressing disruptions,¹⁴ the French society for hospital hygiene recommends to postpone the change of dressing to day 8 after PICC insertion if transparent dressing is used.^2,14 In our study, there was no difference between groups regarding the mean number of dressing changes during the first 8 days. This may be explained by the chosen evaluation time point at day 8. Indeed, the dressing change is scheduled on day 8 when a transparent dressing has been used but when a compress has been needed it is anticipated at day 1 and the subsequent one is planned on day 9. However, another previous study reported that the time for the first dressing change was delayed when using glue, which is de facto the case in the present study population.¹² Similarly, no difference was observed in the number of dressing interventions between groups within the first 30 days.

To our knowledge, PICCandGLUE is the first randomized controlled trial investigating the impact of including cyanoacrylate glue in PICC placement with a 30-day outpatient follow-up period. There were no statistical differences between arms in terms of mechanical, thrombotic, or infectious complications during the first 30 days. Padilla-Nula et al. reported a reduction of PICC migration within the first 24 h (but no difference at 7 days post-intervention) that is not found in our results.⁶ Despite the fact that thrombotic complications appear within the first 14 days, the present study suggests that there is no clinical benefit beyond the insertion procedure, the small sample size not allowing us to judge an effect on thrombotic and infectious complications.¹⁵

The study population was representative of patients undergoing a PICC placement in our vascular access unit. Patients’ characteristics were well-balanced by the centralized randomization procedure, except for a significant difference in the sex ratio between the arms. However, there is no evidence in the literature that gender is associated to a higher risk of bleeding, even after adjustment on the conventional risk factors.¹⁶ Regarding the procedural limitations of our study, it was decided to release the tourniquet as soon as the peelable introducer was placed in the vein; although this choice may result in slightly more bleeding, this procedure was identical in the two groups.

Our primary endpoint reflects the immediate impact of each type of procedure on the patient’s course in the operating room. We considered that the absence of compress need at the time of dressing was associated with an optimal patient course and with no medical disorganization of the medical units. Therefore, it should be highlighted that all patients who had a PICC placement with cyanoacrylate glue were in this optimal setting. However, it would have been more relevant to consider failure as the need to change the dressing before the patient’s discharge. Indeed, the cyanoacrylate glue drastically lowered the rate of patients requiring a change of dressing within the first hour after PICC placement (2% with glue vs 46% without glue).

In conclusion, addition of cyanoacrylate glue provides an immediate benefit at the end of PICC insertion as the transparent dressing can be placed without a compress. The efficacy of the glue lasts from the end of the procedure to the first weekly dressing change, as demonstrated by the lower proportion of patients requiring an unscheduled change of dressing. Ambulatory management of these catheter placements is a challenge, and the glue helps to streamline patient care by reducing the number of nursing procedures. The upcoming organizational impact analysis and health-economics analysis will provide additional insights on the organizational and potential financial benefits.

Footnotes

Author’s note

The PICCandGLUE study (NCT05944900) was a prospective, randomized, controlled-study, conducted in the Vascular Access Unit (VAU) of the Comprehensive Cancer Center Léon Bérard (Lyon, France).

Author contributions

BF: Conceptualization, Investigation, Visualization. ND: Conceptualization, Investigation, Visualization. ADM: Methodology, Formal analysis, Writing—Original Draft. JG: Methodology, Resources, Writing—Original Draft, Visualization, Project administration, Funding acquisition. LB: Software, Quality control of study data, Writing—Original Draft. HR: Conceptualization, Funding acquisition. DP: Conceptualization. GW: Conceptualization, Funding acquisition, Methodology, Investigation, Writing—Original Draft, Supervision.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Essity provided partial financial support and cyanoacrylate glue supply. Essity had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

Ethical approval

The study received regulatory approval from the ethics committee Comité de Protection des Personnes Sud-Est I. No competent authority authorization was required. The study was conducted in accordance with the local regulations in force.

Informed consent

All patients provided a written informed consent prior to study enrollment.

ORCID iD

Grégoire Wallon

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