Patient-Controlled Sedation in Port Implantation (PACSPI-2) -a Randomized Controlled Trial
Phase: PHASE4
Conditions: Pain, Patient Satisfaction, Cancer, Venous Puncture
Sponsor: Region Jönköping County

Patient-controlled Sedation in Port Implantation (PACSPI_3) – patient reported outcome measure on QoR-15 
Studyprotocol 4.0: PACSPI 3 
13-08-2024 
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Study protocol PACSPI 3 
 
TRIAL FULL TITLE 
Patient-controlled Sedation in Port Implantation (PACSPI_3) – 
patient reported outcome measure on QoR-15 
EPM Nr 
EPM amendment Nr 
EPM: 2022-00088-01 
EPM: 2022-00088-02 
EUDRACT NUMBER 
2021-003821-31 
PROTOCOL VERSION 
3.0 
STUDY CODE 
Futurum-963747 
VERSION DATE 
2024-05-22 
TRIAL STATISTICIAN 
Olle Eriksson 
TRIAL SPONSOR 
Knut Taxbro 
TRIAL PRINCIPAL 
INVESTIGATOR 
Stefanie Seifert 
PROTOCOL AUTHOR 
Stefanie Seifert 
 
 
 
 
 
 

Patient-controlled Sedation in Port Implantation (PACSPI_3) – patient reported outcome measure on QoR-15 
Studyprotocol 4.0: PACSPI 3 
13-08-2024 
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Trial Steering Group 
 
Trial Sponsor 
Knut Taxbro 
OP/IVA kliniken  
Ryhov County Hospital 
55185 Jönköping 
Email: knut.taxbro@rjl.se> 
 
Prinicipal Investigator 
Stefanie Seifert 
OP/IVA kliniken  
Ryhov County Hospital 
55185 Jönköping 
Email:   stefanie.seifert@rjl.se> 
 
Co-Investigator 
Fredrik Hammarskjöld 
OP/IVA kliniken  
Ryhov County Hospital 
55185 Jönköping 
Email:  fredrik.hammarskjold@rjl.se> 
 
Co-Investigator 
Josip Azman 
An/OP/IVA kliniken 
Linköping University Hospital 
Email:   Josip.Azman@regionostergotland.se> 
 
Co-Investigator 
Andreas Nilsson 
An/OP/IVA kliniken 
Linköping University Hospital 
Email:  Andreas.Nilsson@regionostergotland.se> 
 
Co-Investigator 
Michelle Chew 
An/OP/IVA kliniken 
Linköping University Hospital 
Email:   Michelle.Chew@regionostergotland.se> 
 
Statistician 
Olle Eriksson 
Futurum 
Ryhov County Hospital 
55185 Jönköping 
Email: olle.eriksson@rjl.se> 
 
Monitor: 
FORUM Östergötland 
Region Östergötland 
Universitetssjukhuset I Linköping 
58185 Linköping 
forumo@regionostergotland.se 

Patient-controlled Sedation in Port Implantation (PACSPI_3) – patient reported outcome measure on QoR-15 
Studyprotocol 4.0: PACSPI 3 
13-08-2024 
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Table of Contents 
1 
Abbreviations and Definitions ................................................................................... 4 
2 
Introduction ......................................................................................................... 5 
2.1 
Purpose of the analyses .................................................................................... 6 
3 
Study Objectives and Endpoints ................................................................................ 6 
3.1 
Study Objectives ............................................................................................. 6 
3.2 
Endpoints ..................................................................................................... 6 
4 
Study Methods ..................................................................................................... 7 
4.1 
General Study Design and Plan ........................................................................... 7 
4.2 
Inclusion-Exclusion Criteria and General Study Population ......................................... 7 
4.3 
Randomisation and Blinding ............................................................................... 7 
4.4 
Study Variables ............................................................................................... 8 
5 
Sample Size .......................................................................................................... 9 
6 
General Considerations ........................................................................................... 9 
6.1 
Timing of Analyses........................................................................................... 9 
6.2 
Analysis Populations ........................................................................................ 9 
6.2.1 
Full Analysis Population .............................................................................. 9 
6.2.2 
Per Protocol Population .............................................................................. 9 
6.2.3 
Intention to treat Population ..................................................................... 10 
6.3 
Missing Data ................................................................................................ 10 
6.4 
Interim Analyses and Data Monitoring ................................................................ 10 
6.4.1 
Documentation of Interim Analyses ............................................................. 10 
6.5 
Multi-centre Studies ...................................................................................... 10 
6.6 
Demographic and Baseline Variables .................................................................. 10 
7 
Statistical Analyses ............................................................................................... 11 
8 
Reporting Conventions ......................................................................................... 11 
9 
Technical Details ................................................................................................. 11 
 
 
 

Patient-controlled Sedation in Port Implantation (PACSPI_3) – patient reported outcome measure on QoR-15 
Studyprotocol 4.0: PACSPI 3 
13-08-2024 
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1 Abbreviations and Definitions 
AE 
Adverse Event 
ASA 
American Society of Anesthesiologists 
CCS 
Clinician-controlled sedation 
CONSORT 
Consolidated Standards of Reporting Trials 
CRF 
Case Report Form 
DSMB 
Data and Safety Monitoring Board 
EPM 
Etikprövningsmyndigheten, Swedish Ethical Review Authority. 
GCP 
Good Clinical Practice 
ITT 
Intention-to-treat 
LA 
Local Anaesthesia 
LMV 
Läkemedelsverket, Swedish medical products agency 
MCID 
Minimal clinically important difference 
NRS 
Numeric Rating Scale 
PACU 
Post Anesthesia Care Unit 
PCS 
Patient-controlled sedation 
QoR-15 swe 
Quality of Recovery-15 swedish 
RCT 
Randomized Controlled Trial 
SFAI 
Swedish Society for Anaesthesia and Intensive Care 
SPOR 
Swedish Perioperative Register 
SVP 
Subcutaneous Venous Port 
TIVAD 
Totally Implantable Venous Access Device 
 
 
 

Patient-controlled Sedation in Port Implantation (PACSPI_3) – patient reported outcome measure on QoR-15 
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13-08-2024 
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2 Introduction 
 
Cancer requiring chemotherapy is common.  Approximately 70.000 patients are diagnosed with 
cancer in Sweden every year often leaving patients in need of intravenous chemotherapy.  
Subcutaneous venous ports (SVP) are commonly used in cancer patients to facilitate intravenous 
administration of chemotherapy, blood sampling and administration of other medications.   
The implantation of SVPs is a minor surgical procedure and one of Sweden´s most common according 
to the Swedish Perioperative Register (SPOR).  SVP implantation is usually performed in a day case 
surgery setting and the patient released home within a few hours after the procedure.   
Conventional outcomes measured after surgery have focused on morbidity, mortality, pain scores, 
analgesic consumption, etc.  However, these measures represent only one aspect of a patient`s 
recovery [1]. 
`Quality of Recovery` scores are patient-reported outcome measures (PROM) evaluating recovery 
after surgery and anaesthesia reflecting the patient`s ability to resume normal activities and are an 
important indicator of a successful perioperative experience [1]. 
The Quality of Recovery-15 (QoR-15) is a psychometrically evaluated instrument with high reliability 
and validity, high responsiveness and good return rates in the postoperative setting [2].  It provides a 
meaningful overall evaluation of a patient´s recovery after surgery [3].  Fifteen questions assess five 
domains of patient-reported health status: pain, physical comfort, physical independence, 
psychological support and emotional state.  The 11-point numerical rating scale leads to a minimum 
score of 0 (very poor recovery) and a maximum score of 150 (excellent recovery).  QoR-15 scores 
negatively correlate with duration of surgery and analgesic usage.  Its minimal clinically important 
difference (MCID) describes the smallest change in score that constitutes a meaningful change in 
health status and is recommended to be a value of six [4].  The Swedish version of QoR-15swe has 
recently been validated [5]. 
A common perception of postoperative recovery in cancer patients undergoing SVP implantation is 
that recovery is good.  We hypothesize that postoperative QoR-15 score is unaffected among patients 
undergoing SVP implantation, randomized to PCS.  To our knowledge no study has investigated 
postoperative recovery after SVP implantation in general and the influence of PCS in particular. 
The aim of this pre-planned sub-study of the PACSPI trial (PACSPI-2, EUDRACT NUMBER 2021-003821-
31) is to assess postoperative recovery, measured as QoR-15 among patients randomized to patient-
controlled sedation (PCS) with alfentanil and propofol as adjunct to local anaesthesia (LA) during SVP 
implantation or standard care with LA.  Patients participating in the study are interviewed with QoR-
15 at three different time points; preoperatively (baseline), postoperatively at the post anaesthesia 
care unit (PACU, before discharge) and 24 hours postoperatively (by telephone).   
 
 
 

Patient-controlled Sedation in Port Implantation (PACSPI_3) – patient reported outcome measure on QoR-15 
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2.1 Purpose of the analyses 
The analyses will assess recovery scores measured by QoR-15.  The analyses will assess if there are 
differences in QoR-15 scores due to PCS intervention. 
3 Study Objectives and Endpoints 
3.1 Study Objectives 
This study measures postoperative outcome of cancer patients undergoing SVP implantation 
evaluated with QoR-15 and the influence of PCS on postoperative recovery.  The study was pre-
planned within `Patient-controlled sedation in subcutaneous port implantation- a randomized 
controlled trial` (PACSPI-2, EUDRACT NUMBER 2021-003821-31) which assesses the efficacy of 
patient-controlled sedation (PCS) with alfentanil and propofol as adjunct to local anaesthesia during 
SVP implantation.  Patients participating in the study are interviewed with QoR-15 at three different 
time points; preoperatively (baseline), postoperative in PACU (before discharge) and 24 hours 
postoperatively (by telephone).  Assessment of QoR-15 scores between groups and time points are 
the study objectives in these analyses. 
 
3.2 Endpoints 
Primary endpoint: 
The primary endpoint is assessment of change in total QoR-15 score between groups at the time 
points. 
 
Secondary endpoints: 
Secondary endpoint is assessment of difference for each QoR dimension and for each of Parts A and B 
within and between groups.  
Secondary endpoint is assessment of analgesic consumption and patient-reported postoperative pain 
perception between groups. 
 
 
 
 

Patient-controlled Sedation in Port Implantation (PACSPI_3) – patient reported outcome measure on QoR-15 
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4 Study Methods 
 
4.1 General Study Design and Plan 
 
This is a pre-planned secondary study of the PACSPI-2 trial (NCT05688384). 
In short: 
The PACSPI-2 trial is an open multicentre randomized controlled trial with a study and a control arm 
in a 1:1 ratio.  Patients are randomized to either a control arm of LA for SVP-implantation or a study 
arm of PCS with propofol and alfentanil as adjunct to LA for SVP-implantation.  The aim is to 
randomize 340 patients with an estimated patient recruitment over 18 months.  The trial is 
performed at two centres; Ryhov County Hospital, Jönköping, Sweden and Linköping University 
Hospital, Sweden.  QoR-15 data is collected during the PACSPI-2 trial.  Secondary outcomes include 
patient satisfaction, implantation conditions, sedation level, sedative and analgesic medication 
consumption, postoperative analgesic requirement, procedural time consumption as well as safety 
aspects and adverse events. 
 
4.2 Inclusion-Exclusion Criteria and General Study Population 
Inclusion criteria:  
o Adult patients (≥18 years) with cancer scheduled for SVP-implantation at participating 
anesthesia departments. 
Exclusion criteria:  
o Inability to operate the PCS apparatus 
o Inability to communicate in Scandinavian languages  
o Patients who require general anesthesia or patients eligible for LA only on anesthesiologist´s 
assessment (i.e. severe sleep apnea) 
o Propofol or alfentanil allergy 
o Non-fasting according to guidelines of the Swedish Society for Anesthesia and Intensive Care 
(SFAI) 
o Failure to achieve peripheral vascular access 
o Pregnancy  
o Previous participation in study 
 
4.3 Randomisation and Blinding 
Prior to SVP-implantation and when the patient´s eligibility has been confirmed and consent forms 
have been completed the patient is randomized by password-coded randomization software 
accessible to the co-investigators at each participating site (REDCap).  All patients are randomized 
onto the study prior to SVP-implantation. 

Patient-controlled Sedation in Port Implantation (PACSPI_3) – patient reported outcome measure on QoR-15 
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Each patient randomized will be allocated a unique sequential patient code number for the 
randomization arm together with an allocated study arm. 
The randomization scheme is equal allocation (1:1).  Randomization will be performed consecutively.  
If a patient withdraws from the trial the unique patient code will not be used again and the patient 
will not be included into the trial again. 
 
4.4 Study Variables 
All measured study variables are described in the PACSPI-2 study protocol accessible on 
clinicaltrials.gov (NCT05688384).   
QoR-15swe (Quality of Recovery-15 Sweden) is measured on a numeric rating scale (NRS) from 0 to 
10. 
The score in the separate dimensions will be combined into a single value as expression for total QoR-
15 score. 
Del A  
Hur har du mått de senaste 24 timmarna?   
På en skala från 0 till 10, där 0 = Inte någon gång {dåligt} och 10 = hela tiden {utmärkt}  
  
 
1 
 
Kunnat andas lugnt 
  
Inte någon gång  
 
0 
 
1 
 
2 
 
3 
 
4 
 
5 
 
6 
 
7 
 
8 
 
9 
 
10 
  
hela tiden  
 
2 
 
Kunnat njuta av maten 
  
Inte någon gång  
 
0 
 
1 
 
2 
 
3 
 
4 
 
5 
 
6 
 
7 
 
8 
 
9 
 
10 
 
hela tiden  
 
3 
 
Känt dig utvilad 
  
Inte någon gång  
 
0 
 
1 
 
2 
 
3 
 
4 
 
5 
 
6 
 
7 
 
8 
 
9 
 
10 
  
hela tiden  
 
4 
 
Kunnat sova gott 
  
Inte någon gång  
 
0 
 
1 
 
2 
 
3 
 
4 
 
5 
 
6 
 
7 
 
8 
 
9 
 
10 
 
hela tiden  
 
5 
Kunnat sköta toalettbesök och personlig 
hygien utan hjälp 
  
Inte någon gång  
 
0 
 
1 
 
2 
 
3 
 
4 
 
5 
 
6 
 
7 
 
8 
 
9 
 
10 
 
hela tiden  
 
6 
Kunnat kommunicera med anhöriga eller 
vänner   
  
Inte någon gång  
 
0 
 
1 
 
2 
 
3 
 
4 
 
5 
 
6 
 
7 
 
8 
 
9 
 
10 
 
hela tiden  
 
7 
Fått stöd från sjukhuspersonal 
 
  
Inte någon gång  
 
0 
 
1 
 
2 
 
3 
 
4 
 
5 
 
6 
 
7 
 
8 
 
9 
 
10 
 
hela tiden  
 
8 
Kan du utföra ditt arbete eller dina 
vanliga aktiviteter hemma 
  
Inte någon gång  
 
0 
 
1 
 
2 
 
3 
 
4 
 
5 
 
6 
 
7 
 
8 
 
9 
 
10 
 
hela tiden  
 
9 
Känt dig trygg och haft kontroll över din 
tillvaro 
  
Inte någon gång  
 
0 
 
1 
 
2 
 
3 
 
4 
 
5 
 
6 
 
7 
 
8 
 
9 
 
10 
 
hela tiden  
 
10 
Haft en känsla av allmänt välbefinnande 
 
  
Inte någon gång 
 
0 
 
1 
 
2 
 
3 
 
4 
 
5 
 
6 
 
7 
 
8 
 
9 
 
10 
 
hela tiden 
 
Del B  
Har du känt något av följande symptom de senaste 24 timmarna?   
på en skala från 10 till 0,där 10 = Inte någon gång {utmärkt} och 0 = hela tiden {dåligt}  
 
11 
Medelsvår smärta 
 Inte någon gång  
10 
9 
8 
7 
6 
5 
4 
3 
2 
1 
0 
hela tiden  
12 
Svår smärta  
 Inte någon gång  
10 
9 
8 
7 
6 
5 
4 
3 
2 
1 
0 
hela tiden  

Patient-controlled Sedation in Port Implantation (PACSPI_3) – patient reported outcome measure on QoR-15 
Studyprotocol 4.0: PACSPI 3 
13-08-2024 
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13 
Illamående eller kräkning 
 Inte någon gång  
10 
9 
8 
7 
6 
5 
4 
3 
2 
1 
0 
hela tiden  
14 
Känt ångest eller oro  
 Inte någon gång  
10 
9 
8 
7 
6 
5 
4 
3 
2 
1 
0 
hela tiden  
15 
Känt dig ledsen eller deprimerad  
 Inte någon gång 
10 
9 
8 
7 
6 
5 
4 
3 
2 
1 
0 
hela tiden 
 
 
Time table for measurement of variables 
 
Preop 
Intraop 
Postop 
f
24h postop 
l
h
QoR-15swe 
x 
 
x 
x 
Demographic 
x 
 
 
 
Vital signs 
x 
x 
 
 
Procedure details 
 
x 
 
 
Malignancy details 
x 
 
 
 
Sedation assessment 
 
x 
 
 
AE/SAE 
 
x 
 
 
Analgesia 
 
x 
 
x 
Time consumption 
x 
x 
x 
 
 
5 Sample Size  
Sample size calculation in the original trial was performed on its primary endpoint with the aim to 
detect a 50% reduction in pain perception as stated by the study protocol. 340 patients are included 
in the study with a 1:1 randomization.  
Considering a minimal clinically important difference (MCID) of 6 that has been suggested to 
constitute a meaningful change in health status with a standard deviation of 19 a total number of 314 
patients is needed to detect this change with 80% power, 2-sided, at a significance level of 5%. 
 
 
6 General Considerations 
6.1 Timing of Analyses 
The final analysis will be performed after 340 patients have been included.   
 
6.2 Analysis Populations 
6.2.1 
Full Analysis Population 
All participants who were randomized. 
6.2.2 
Per Protocol Population 
All participants who received a SVP. 

Patient-controlled Sedation in Port Implantation (PACSPI_3) – patient reported outcome measure on QoR-15 
Studyprotocol 4.0: PACSPI 3 
13-08-2024 
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6.2.3 
Intention to treat Population 
Analyses will be performed on all participants in the original assigned randomized group. 
 
6.3 Missing Data 
Missing data are assumed of missing at random (MAR).  Less than 10 % of data are assumed missing. 
Missing data will be quantified and reported. 
 
6.4 Interim Analyses and Data Monitoring 
Interim analyses are not expected to lead to early closure of neither randomization on safety nor 
efficacy grounds.  Both techniques are established and clinically approved methods and complications 
are very uncommon.  After 100 respectively 200 patients analyses of adverse events (AE) will be 
performed in which we expect a frequency lower than 15% based on previous studies (PACSPI1).  In 
the event of a higher frequency the sponsor will discuss further action with the monitor.  
6.4.1 
Documentation of Interim Analyses 
Snapshots of the data available at each interim analysis will be preserved.  Reports of AE analyses will 
be stored in the sponsor`s documents enabling recreating the decision process from the trial archive. 
 
6.5 Multi-centre Studies 
This trial will be carried out in the following anaesthesia departments: 
OP/IVA-klinken, Ryhov County Hospital, Sweden 
AnOpIVA-kliniken, Linköping University Hospital, Sweden 
 
Co-investigators at participating sites will have access to REDCap.  Centres are provided with the PCS 
pump.  There will be no restrictions in the choice of LA-solution being left up to local practice at 
participating sites 
 
6.6 Demographic and Baseline Variables 
Gender, age, American Society of Anestesiologists (ASA)-class, BMI, cancer type, treatment strategy, 
preoperative analgesia, procedural time, sedation score at timepoints T1-4 (OAAS), sedation volym, 
alfentanil (mg) delivered, propofol (mg) delivered will be reported for demographic and interventional 
data.   
 
 

Patient-controlled Sedation in Port Implantation (PACSPI_3) – patient reported outcome measure on QoR-15 
Studyprotocol 4.0: PACSPI 3 
13-08-2024 
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7 Statistical Analyses 
The analysis will be produced on intention to treat population. 
 
Data will be summarised by treatment group.  Summary statistics of demographic and baseline 
variables will be reported.  All continuous variables will be summarised using the following descriptive 
statistics: n (non-missing sample size), median, interquartile range.  The frequency and percentages 
(based on the non-missing sample size) of observed levels will be reported for all categorical 
measures.  Categorical data will be analysed with Chi2 test, continuous data will be analysed with 
Mann-Whitney U test. 
 
Repeated measurement of analysis of variance is used for the analysis of treatment effect of PCS on 
QoR-15 scores.  This model takes the inter- and intra-individual variation into account and provides 
flexibility in handling missing data which will be reported.  Fixed factors include treatment group, time 
and treatment-by time-interaction.  Confidence intervals will be reported and adjustment for planned 
comparison conducted.  Testing will be two-sided with a 5% significance level. 
 
Demographic and baseline data will be listed by treatment group in a table. 
Primary endpoint will be displayed in a figure. 
Secondary endpoints will be displayed in a figure. 
 
8 Reporting Conventions 
P-values  ≥ 0.01 will be reported to two decimal places,  p-values ≥0.001 will be reported to three 
decimal places; p-values less than 0.001 will be reported as “<0.001”.  The median and any other 
statistics other than quantiles, will be reported to one decimal place greater than the original data. 
 
9 Technical Details 
Analyses will be carried out with the study statistician.  Analyses will be carried out in SPPS, IBM 
 
 
 
 
 
 

Patient-controlled Sedation in Port Implantation (PACSPI_3) – patient reported outcome measure on QoR-15 
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References 
 
1. 
Chazapis M, Walker EM, Rooms MA, Kamming D, Moonesinghe SR. (2016). Measuring quality 
of recovery-15 after day case surgery. Br J Anaesth;116(2):241-8. 
http://dx.doi.org/10.1093/bja/aev413.  
2. 
Stark PA, Myles PS, Burke JA. (2013). Development and psychometric evaluation of a 
postoperative quality of recovery score: the QoR-15. Anesthesiology;118(6):1332-40. 
http://dx.doi.org/10.1097/ALN.0b013e318289b84b.  
3. 
Myles PS. (2018). Measuring quality of recovery in perioperative clinical trials. Curr Opin 
Anaesthesiol;31(4):396-401. http://dx.doi.org/10.1097/aco.0000000000000612.  
4. 
Myles PS, Myles DB. (2021). An Updated Minimal Clinically Important Difference for the QoR-
15 Scale. Anesthesiology;135(5):934-5. http://dx.doi.org/10.1097/aln.0000000000003977.  
5. 
Lyckner S, Böregård IL, Zetterlund EL, Chew MS. (2018). Validation of the Swedish version of 
Quality of Recovery score -15: a multicentre, cohort study. Acta Anaesthesiol Scand;62(7):893-902. 
http://dx.doi.org/10.1111/aas.13086.