Central Venous Catheter vs Midline in Difficulty Access Patient - A Randomized Controlled Clinical Pilot Trial - Pilot-ACCESS-D
Phase: NA
Conditions: Difficult Intravenous Access
Sponsor: Region Jönköping County

Research plan:  
Central Venous Catheter vs Midline in 
Difficulty Access patient – A Randomized 
controlled clinical pilot trial – pilot-ACCESS-
D 
Content 
Overview: .................................................................................................................................... 2 
Introduction ................................................................................................................................ 3 
Methods ...................................................................................................................................... 4 
 
Last revised: 20 February 2025 
EPM:  
First: Dnr 2024-02365-01, Approved 22 April 2024 
Second: Dnr 2024-05700-01, Approved 18 September 2024 
 
CIP-kod: CVMID 
CIV-ID: CIV-24-08-048798 
ClinicalTrials.gov ID: NCT06719869 
 
 
 
 
 
 
 

Overview: 
Title: 
1. Midline vs. Central Venous Catheter for Difficult Venous Access patients (ACCESS-D 
study) – A pilot trial 
Study method: Randomized controlled clinical pilot trial 
Purpose: To examine the feasibility of the ACCESS-D trial. 
Population: 18+ age difficult intravenous access patients with expected 4-29 days of catheter 
dwell time in Ryhov Hospital, identified through the Acute care and Trauma unit (ATE). 
 
 
Abbreviations: 
CVC – Central venous catheter 
DIVA – Difficult intravenous access 
PICC – Peripherally inserted central catheter 
PVC – Peripheral venous catheter 
RCT – Randomized controlled clinical trial 
USG – Ultrasound guided 
VAD – Vascular access device 
 
 
 

Introduction 
 
Intravenous access is a necessity for nearly all inpatient medical care. Approximately half of 
hospitalized patients require a peripheral venous catheter (PVC), either to enable administration 
of medications intravenously or to repeatedly draw blood samples (1). Establishing a venous 
access sometimes requires repeated attempts, resulting in multiple needle sticks and prolonged 
discomfort for patients. In addition, this may lead to a diminished healthcare experience and 
create a stressful situation for both patients and healthcare personnel (2, 3). Delays in 
establishing intravenous access can result in setbacks in sample collection and drug 
administration (4, 5). 
Difficult Intravenous Access (DIVA) is a situation that arises “when two or more clinicians fail 
two or more times to establish a peripheral access using conventional techniques, when a patient 
lacks visible or palpable veins or the patient has a stated or documented history of DIVA” (6). 
The prevalence of DIVA varies from 6% to 88% in different studies, primarily due to variations 
in definition of DIVA. Known risk factors are diabetes, intravenous drug abuse, sex (higher risk 
for women), chronic illness, obesity, malnutrition, absence of visible or palpable veins (7, 8). 
Although it is possible to establish a short, standard-length PVC through the help of ultrasound-
guidance, this approach has limited scientific support (4, 9-11). In addition, ultrasound-guided 
PVCs are not health economically justifiable (12). 
There are a handful of alternatives in terms of vascular access devices (VAD) for DIVA patients: 
Standard short PVC, Midline catheter, Central Venous Catheter (CVC) and Peripherally 
Inserted Central Catheter (PICC). A Midline is a long (8-12 cm), peripherally inserted venous 
catheter that is most commonly inserted into the upper arm via the basilic, cephalic or brachial 
veins, with its tip terminating below the level of the axilla (13). A Central Venous Catheter 
(CVC) is inserted through one of several veins (subclavian, jugular, or femoral) and terminates 
in a central vein, typically the superior vena cava, right atrium, or the iliac/inferior vena cava, 
depending on the insertion site. A PICC is an extended venous catheter inserted peripherally, 
similar to the Midline, inserted through the veins of the upper arm. However, the PICC 
terminates centrally, in the superior vena cava. There is some existing evidence supporting that 
Midline catheters could be safer compared to PICCs in short term (14-16). Today, CVCs are 
standard of care in many centers, but retrospective data indicate that Midlines could be a 
feasible option in DIVA patients (17). Furthermore, CVC insertion involves certain risks, such 
as arterial puncture, hematoma or pneumothorax (18). For DIVA patients in need of venous 

access for 5 days or more, Midlines are preferred as per the Michigan Appropriateness Guide 
for Intravenous Catheters (MAGIC) guidelines (13). However, there are no randomized 
controlled clinical trials comparing Midlines to CVCs in DIVA patients. 
Primary aim of study 
The aim of the study is to test the feasibility of the study protocol before a future large-scale 
RCT. 
Methods 
CONSORT Methods  
This pilot trial is a randomized, controlled, two-armed study with a sample size of 30 patients. 
A sample size of 30 is chosen as a convenience sample. The study will be conducted in Ryhov 
county hospital, in southern Sweden. Hospitalized patients across adult somatic wards with 
difficult intravenous access, are screened for potential trial recruitment. Patients are identified 
when staff from the ward contact the vascular access nurse. All inclusion and exclusion criteria 
are presented in Table 1. Patients identified, screened, and deemed eligible will be approached 
with study information. The trial is planned in accordance with the CONSORT guidelines for 
pilot trials (19). 
Table 1 Inclusion and exclusion criteria 
Inclusion Criteria 
Exclusion Criteria 
• Age 18 and over 
• Unable to speak Scandinavian 
• DIVA criterium fulfilled;  
o 2 attempts of venous access 
by 2 clinicians 
OR 
o No visible nor palpable veins 
OR 
o History of difficult venous 
access 
• Cognitive Impairment 
• Is to receive hyperosmolar solutions 
(600 milliosmoles/L or above). 
• Is to receive chemotherapy 
• 4 - 29 days of catheter dwell time 
anticipated as assessed by referring 
clinician. 
 
 
 

Setting 
The patient flowchart, depicted in Figure 1, outlines the vascular access procedures at Ryhov 
County Hospital. This process involves collaboration between a ward nurse and an anesthesia 
(vascular access) nurse. In case the ward nurse encounters difficulties in establishing venous 
access, patients are referred to the anesthesia nurse accordingly. 
The insertion of catheters occurs in a dedicated post-op area. Clinicians in this setting have the 
option to choose between establishing a Midline catheter guided by ultrasound or opting for a 
Central Venous Catheter (CVC), also guided by ultrasound (USG). 
Recruitment, Randomization and Blinding 
Patients are assessed by the vascular access clinician in the Post-op ward. The recruitment 
process takes place in collaboration with anesthesiologists from the Acute Care and Trauma 
unit. Written consent and information are obtained by the physician. Subsequently, patients are 
randomized by the trial clinician using StudyRandomizer (https://www.studyrandomizer.com). 
Due to the visible nature of the intervention, blinding is not feasible. Trial participants are 
randomized in a 1:1 ratio using a block size of 6.  
Patient identification, screening, and recruitment are outlined in Figure 1. After obtaining 
written consent, randomization, allocation and insertion of the   VAD, patients return to their 
respective wards.  

 
 
 
Intervention, Midline:  
Patients in the intervention group receive a 10 cm PowerGlide Pro™ Midline Catheter (Becton 
Dickinson). Catheters are inserted with ultrasound-guidance by an anesthesiologist using sterile 
gloves, mask, and large drape. The insertion site is treated with a solution of 0.5% chlorhexidine 
(wt/vol) in 70% alcohol (SCHA) and allowed to dry for 1 to 2 minutes prior to insertion. No 
prophylactic antibiotics are given as per default. All catheters are secured with using a 
Ward Nurse/Anesthesia 
nurse contacted by ward 
Unsuccessful 
establishment of VAD in 
ward 
Patient relocated to 
Post-op area 
Patient is eligible: 
•
In need of VAD 
4-29 days 
•
DIVA Criterium 
•
Age 18 or above 
Recruitment             Assessment 
Screening 
Successful establishment 
of VAD in ward 
Patients recruited and 
Randomized 
Allocation 
Exclusion criteria met 
Declined to participate 
Does not receive 
allocated treatment 
Figure 1: Flowchart of screening, assessment, recruitment and allocation in study. 

StatLock™ Stabilization device (Becton Dickinson), and the site is dressed with a 
semipermeable dressing (Tegaderm HP; 3M Healthcare, St. Paul, MN). A red paper tag is 
attached to the catheter, indicating study participation. Choice of insertion site on arm below or 
above the elbow avoiding catheter across joints and at the clinician’s discretion. 
Control, Central Venous Catheter (CVC): 
Patients in the control group receive a Celsite 320 or 315 (B. Braun) or Pressure Injectable 
Arrowg+ard Blue Plus+ (Arrow). Catheters are inserted with ultrasound-guidance by an 
anesthesiologist with maximal sterile precautions (cap, mask, gown, gloves, and large drape) 
using the Seldinger technique. The insertion site is treated with a solution of 0.5% chlorhexidine 
(wt/vol) in 70% alcohol (SCHA) and allowed to dry for 1 to 2 minutes prior to insertion. No 
prophylactic antibiotics are given as per default. Catheters are secured with monofilament 
sutures, and the site is dressed with a semipermeable dressing (Tegaderm HP; 3M Healthcare, 
St. Paul, MN). A red paper tag is attached to the catheter, indicating study participation. The 
choice of insertion site is at the clinician’s discretion. 
Catheter care 
Catheters (Midline and CVC) are controlled daily by the ward nurse. Control includes 
inspection of dressing, puncture site, the catheter itself and tags. The catheter function is 
assessed and flushed with minimum 20mL saline solution daily and in conjunction to use.  For 
CVCs dressing is replaced every third day or earlier if necessary. Extension tubing, three-way 
connectors and injection valves are replaced every third day or earlier if necessary. With 
Midline, StatLock™ Stabilization device is replaced every 7th day or earlier if necessary. 
Outcomes 
The main outcomes are related to feasibility. Feasibility is defined as eligibility (>50% of 
screened patients considered eligible), recruitment (>70% of eligible patients consent to partake 
in trial), retention and attrition (<10% of patients lost to follow up, including those who 
withdrew consent), adherence (>80% of enrolled patients receive their randomized 
intervention), missing data (<10% of enrolled patients data missing) and venipuncture attempts 
(<20% of enrolled patients receive 2 venipunctures per insertion). 
The secondary outcomes are insertion time and dwell time measured in minutes and days 
respectively. Catheter complications (infection, thrombosis and mechanical failure) are 
measured by objectively through bacterial culture, radiology and clinical expertise as per 

standard clinical routine. Catheter complications during insertion and reason for removal are 
also registered during follow-up. 
 
Follow-up 
Follow-up will be performed in-ward every Monday and every Thursday by a research nurse 
or research assistant. Follow-up will be performed until the catheter is removed or until 28 days. 
Patients who are discharged from hospital with their catheter in situ will be followed through 
telephone interviews and chart reviews of out-patient notes  
Ethical considerations 
Ethical approval from the Swedish Ethical Review Authority is mandatory prior to trial start. 
The trial will be carried out in accordance with the study protocol under the principles of the 
Helsinki Declaration. The trial and study protocol will be prospectively registered on 
www.clinicaltrials.gov.  
Regardless of whether a patient participates in the study, the need for venous access remains. 
Both midline catheters and CVCs are well-established methods for securing venous access, and 
the study presents no significant disadvantages or ethical concerns associated with their 
implementation. 
Participation in the trial is entirely voluntary and is based on informed and signed consent. 
Participants have the right to withdraw their consent at any time for any reason, without 
prejudice to their medical care. Comprehensive oral and written information about the trial will 
be provided to participants before obtaining their consent and before their inclusion in the study. 
The research material will be stored in a secure safe where the research team have exclusive 
access. 
Statistical analysis     
Descriptive statistics are used to outline patients’ baseline characteristics. For measurements 
that follow a normal distribution, group differences will be assessed using Student's t-test. 
Given the small sample size of 30, Mann-Whitney U test will be used to calculate differences 
in dwell time and insertion time between groups. 
 

Funding 
Carl Mellander has 25% part-time research funded by RJL and LiU. 
 
Time plan (revised December 2024):  
2024 Q1: Protocol construction 
2024 Q2: Protocol submitted to Ethics Review Board 
2025 Q1: Study start (January 13) 
2025 Q2: Data analysis and manuscript 
 
 
 
 
 
 
 
 
 
 

Results 
 
Figure X: Patient flowchart according to CONSORT. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Assessed for eligibility 
 (n = …) 
Excluded (n = …) 
  Not meeting inclusion criteria (n = …) 
  Refused to participate (n = …) 
  Other reasons (n = …) 
Randomized (n = …) 
Allocated to 
intervention (n = …) 
Received allocated 
intervention (n = …) 
Did not receive allocated 
intervention (n = …) 
(give reasons) 
Allocation 
 
 
Enrollment 
Allocated to 
intervention (n = …) 
Received allocated 
intervention (n = …) 
Did not receive allocated 
intervention (n = …)  
(give reasons) 
Follow up 
Lost to follow up  
(n = …) (give reasons) 
Discontinued intervention 
(n = …) (give reasons) 
Lost to follow up  
(n = …) (give reasons) 
Discontinued intervention 
(n = …) (give reasons) 
Analyzed (n = …) 
Excluded from analysis (n = …) 
(give reasons) 
Analyzed (n = …) 
Excluded from analysis (n = …) 
(give reasons) 

 
References 
1. 
Alexandrou E, Ray-Barruel G, Carr PJ, Frost S, Inwood S, Higgins N, et al. International 
prevalence of the use of peripheral intravenous catheters. Journal of Hospital Medicine. 
2015;10(8):530-3. 
2. 
Schults JA, Calleja P, Slaughter E, Paterson R, Rickard CM, Booker C, et al. Peripheral 
intravenous catheter insertion and use of ultrasound in patients with difficult intravenous access: 
Australian patient and practitioner perspectives to inform future implementation strategies. PLOS 
ONE. 2022;17(6):e0269788. 
3. 
Robinson-Reilly M, Paliadelis P, Cruickshank M. Venous access: the patient experience. 
Supportive Care in Cancer. 2016;24(3):1181-7. 
4. 
Stolz LA, Stolz U, Howe C, Farrell IJ, Adhikari S. Ultrasound-guided peripheral venous 
access: a meta-analysis and systematic review. J Vasc Access. 2015;16(4):321-6. 
5. 
Witting MD. IV Access Difficulty: Incidence and Delays in an Urban 
Emergency Department. The Journal of Emergency Medicine. 2012;42(4):483-7. 
6. 
Bahl A, Johnson S, Alsbrooks K, Mares A, Gala S, Hoerauf K. Defining difficult 
intravenous access (DIVA): A systematic review. The Journal of Vascular Access. 
2021;0(0):11297298211059648. 
7. 
Whalen M, Maliszewski B, Baptiste DL. Establishing a Dedicated Difficult Vascular 
Access Team in the Emergency Department: A Needs Assessment. J Infus Nurs. 2017;40(3):149-54. 
8. 
Sebbane M, Claret PG, Lefebvre S, Mercier G, Rubenovitch J, Jreige R, et al. Predicting 
peripheral venous access difficulty in the emergency department using body mass index and a clinical 
evaluation of venous accessibility. J Emerg Med. 2013;44(2):299-305. 
9. 
Sou V, McManus C, Mifflin N, Frost SA, Ale J, Alexandrou E. A clinical pathway for the 
management of difficult venous access. BMC Nursing. 2017;16(1):64. 
10. 
Liu YT, Alsaawi A, Bjornsson HM. Ultrasound-guided peripheral venous access: a 
systematic review of randomized-controlled trials. Eur J Emerg Med. 2014;21(1):18-23. 
11. 
Pavelkova K, Lisova K, Blahova P, Mokra D, Hloch O, Charvat J. Comparison of 12-cm 
versus 6-cm long peripheral catheters in patients with difficult intravenous access (DIVA). J Vasc 
Access. 2022;23(1):94-7. 
12. 
Gala S, Alsbrooks K, Bahl A, Wimmer M. The economic burden of difficult intravenous 
access in the emergency department from a United States’ provider perspective. Journal of Research 
in Nursing. 2024;0(0):17449871231213025. 
13. 
Moureau N, Chopra V. Indications for peripheral, midline and central catheters: 
summary of the MAGIC recommendations. Br J Nurs. 2016;25(8):S15-24. 
14. 
Swaminathan L, Flanders S, Horowitz J, Zhang Q, O'Malley M, Chopra V. Safety and 
Outcomes of Midline Catheters vs Peripherally Inserted Central Catheters for Patients With Short-
term Indications: A Multicenter Study. JAMA Intern Med. 2022;182(1):50-8. 
15. 
Urtecho M, Torres Roldan VD, Nayfeh T, Espinoza Suarez NR, Ranganath N, 
Sampathkumar P, et al. Comparing Complication Rates of Midline Catheter vs Peripherally Inserted 
Central Catheter. A Systematic Review and Meta-analysis. Open Forum Infect Dis. 
2023;10(2):ofad024. 
16. 
Chopra V, Flanders SA, Saint S, Woller SC, O'Grady NP, Safdar N, et al. The Michigan 
Appropriateness Guide for Intravenous Catheters (MAGIC): Results From a Multispecialty Panel Using 
the RAND/UCLA Appropriateness Method. Ann Intern Med. 2015;163(6 Suppl):S1-40. 
17. 
Mushtaq A, Navalkele B, Kaur M, Krishna A, Saleem A, Rana N, et al. Comparison of 
complications in midlines versus central venous catheters: Are midlines safer than central venous 
lines? American Journal of Infection Control. 2018;46(7):788-92. 
18. 
Lennon M, Zaw NN, Pöpping DM, Wenk M. Procedural complications of central venous 
catheter insertion. Minerva Anestesiol. 2012;78(11):1234-40. 

19. 
Eldridge SM, Chan CL, Campbell MJ, Bond CM, Hopewell S, Thabane L, et al. CONSORT 
2010 statement: extension to randomised pilot and feasibility trials. BMJ. 2016;355:i5239.