Colchicine Treatment for Patients With Hand Osteoarthritis: A Randomised, Placebo-controlled Trial.
Phase: PHASE4
Conditions: Osteoarthritis Hand, Osteoarthritis Finger
Sponsor: Henning Bliddal

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
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CLINICAL STUDY PROTOCOL 
Colchicine treatment for patients with hand osteoarthritis: A randomised, placebo-
controlled trial. 
Anna Døssing, Karen Ellegaard, Lisa Stamp, Christoph Felix Müller, Margreet Kloppenburg, Ida K.  Haugen, 
Geraldine McCarthy, Philip Conaghan, Lene Terslev, Roy D. Altman, Fabio Becce, Elisabeth Marie Ginnerup-
Nielsen, Mikael Boesen, Robin Christensen, Henning Bliddal, Marius Henriksen 
 
Investigator:  
Henning Bliddal, MD, DMSc 
Sponsor: 
Henning Bliddal, MD, DMSc 
Sponsor & 
investigator site: 
The Parker Institute, Bispebjerg and Frederiksberg Hospital, Ndr. Fasanvej 57, DK-
2000 Frederiksberg, Denmark. Telephone: +45 38 16 41 55. 
Collaborators 
Department of Radiology, Bispebjerg and Frederiksberg Hospital, Bispebjerg Bakke 
23, 2400 København V, Denmark.  
GCP-unit by Copenhagen University Hospital, Bispebjerg and 
Frederiksberg Hospital, Nordre Fasanvej 57, Skadestuevej 1, parterre, 2000 
Frederiksberg, Denmark.  
Central pharmacy of the capital region (Region H), Marielundvej 25, 2730 Herlev, 
Denmark.  
 
 
 
 
 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 2 af 65 
 
1.1 Affiliations 
Anna Døssing, MD: The Parker Institute, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, 
Copenhagen, Denmark. Email: anna.doessing.01@regionh.dk. 
 
Felix C. Müller, MD: Department of Radiology, Herlev and Gentofte Hospital, University of Copenhagen, 
Copenhagen, Denmark. Email: Christoph.felix.mueller@regionh.dk. 
 
Karen Ellegaard, PT, PhD: The Parker Institute, Bispebjerg and Frederiksberg Hospital, University of 
Copenhagen, Copenhagen, Denmark. Email: karen.ellegaard@regionh.dk. 
 
Geraldine McCarthy, MD, FRCPI: Clinical Professor of Medicine, School of Medicine and Medical Science, 
University College Dublin, United Kingdom. Email: g.mccarthy@ucd.ie. 
 
Philip Conaghan, MD, MBBS, PhD, FRACP, FRCP: Leeds Institute of Rheumatic and Musculoskeletal 
Medicine, University of Leeds and National Institute for Health Research Leeds Biomedical Research Centre, 
Leeds, UK. Email: P.Conaghan@leeds.ac.uk 
 
Roy D. Altman, MD: Professor of Medicine, Division of Rheumatology and Immunology, The David Geffen 
School of Medicins at the University of California at Los Angeles (UCLA), Los Angeles, California, USA.  Email: 
journals@royaltman.com. 
 
Lisa Stamp, FRACP, PhD: Department of Medicine, University of Otago, Christchurch, New Zealand. Email: 
lisa.stamp@cdhb.health.nz 
 
Lene Terslev, MD PhD: Center for Rheumatology and Spine Diseases, Rigshospitalet, University of 
Copenhagen, Copenhagen, Denmark. Email: lene.terslev.01@regionh.dk 
 
Margreet Kloppenburg: , MD PhD: Departments of Rheumatology and Clinical Epidemiology, Leiden 
University Medical Center, Leiden, The Netherlands. Email: g.kloppenburg@lumc.nl 
 
Ida K. Haugen, MD PhD: Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. Email: 
Ida.haugen@diakonsyk.no 
 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
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Elisabeth Marie Ginnerup-Nielsen, PT, MHS: The Parker Institute, Bispebjerg and Frederiksberg Hospital 
University of Copenhagen, Copenhagen, Denmark. Email: elisabeth.marie.ginnerup-nielsen@regionh.dk 
 
Fabio Becce, MD: Department of Diagnostic and Interventional Radiology, Lausanne University Hospital and 
University of Lausanne, Lausanne, Switzerland. Email: fabio.becce@chuv.ch 
 
Mikael Boesen, MD, PhD: Department of Radiology, Bispebjerg and Frederiksberg Hospital, University of 
Copenhagen, Copenhagen Denmark: Email: mikael.ploug.boesen@regionh.dk.’ 
 
Robin Christensen, MSc, PhD: Musculoskeletal Statistics Unit, The Parker Institute, Bispebjerg and 
Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark. Research Unit of Rheumatology, 
Department of Clinical Research, University of Southern Denmark, Odense University Hospital, Denmark. 
Email: Robin.Christensen@Regionh.dk. 
 
Henning Bliddal, MD, DMSc: The Parker Institute, Bispebjerg and Frederiksberg Hospital, University of 
Copenhagen, Copenhagen, Denmark. Email: Henning.Bliddal@regionh.dk. 
 
Marius Henriksen, PT, PhD: The Parker Institute, Bispebjerg and Frederiksberg Hospital, University of 
Copenhagen, Copenhagen, Denmark. Email: marius.henriksen@Regionh.dk. 
 
 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
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2 ABSTRACT 
Background: Pharmacological treatment recommendations for hand osteoarthritis (OA) are focused around 
analgesics that are not targeted at the disease and new treatment strategies are explored continuously. 
Crystal deposits have been proposed to play a role in the progression of hand OA and may provide an 
explanation for inflammatory flares. In people with gout and monosodium urate crystal deposits, 
inflammation and pain can be treated successfully with oral colchicine. This study will assess the 
effectiveness of oral colchicine for people with hand OA. 
Methods: The COLchicine treatment for patients with hand OsteoaRthrithis (COLOR) trial will be a double-
blind, randomised, placebo-controlled trial. A total of 100 patients with painful hand OA will be included. 
Participants will be recruited from a single centre in Denmark. Participants will be randomised 1:1 to 
achieve oral treatment with colchicine one tablet (0.5 mg) or placebo one tablet bid (twice a day) for 12 
weeks. The primary outcome is change in finger joint pain measured on a visual analogue scale spanning 
from 0 (no pain) to 100 (worst imaginable pain). Secondary outcomes include improvement in function, 
joint activity measured on physician tender joint count, patient global assessment, hand strength, and 
health-related quality of life. Inflammation and crystal deposits will be assessed at baseline as exploratory 
contextual factors measured on ultrasound, dual-energy computed tomography, and cone-beam computed 
tomography, respectively. Mixed models with repeated measurements, and adjustment for baseline 
measures will be used to compare changes between groups in the intention-to-treat population after 12 
weeks. 
Discussion: The COLOR trial is designed to evaluate whether oral colchicine is effective for improving pain 
in people with painful hand OA. Exploratory analysis will assess if crystal deposition is a predictor of 
therapeutic response. This study will potentially provide data to support a new treatment option for hand 
OA that can be managed by both rheumatologist and non-rheumatological doctors in primary and 
secondary care. 
 
Keywords: Hand Osteoarthritis. Colchicine. Crystal deposition. Double-blind. Placebo-controlled. 
Randomised.  
 
 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 5 af 65 
 
TABLE OF CONTENT 
1.1 
Affiliations .......................................................................................................................................... 2 
2 
ABSTRACT.................................................................................................................................................. 4 
TABLE OF CONTENT ........................................................................................................................................... 5 
3 
ABBREVIATIONS ...................................................................................................................................... 10 
4 
TRIAL IDENTIFIER .................................................................................................................................... 12 
4.1 
Full title of trial ................................................................................................................................ 12 
4.2 
Acronym .......................................................................................................................................... 12 
4.3 
Short title ......................................................................................................................................... 12 
4.4 
Health Research Ethics Committee Number ................................................................................... 12 
4.5 
European clinical trials database (EudraCT number) ...................................................................... 12 
4.6 
Version number and date ................................................................................................................ 12 
4.7 
Revision history ............................................................................................................................... 12 
4.7.1 
Table 1: Revision history .......................................................................................................... 12 
4.8 
Expected timeline ............................................................................................................................ 13 
5 
INTRODUCTION ....................................................................................................................................... 13 
5.1 
Background ...................................................................................................................................... 13 
5.2 
Rationale and evidence-based research.......................................................................................... 13 
5.3 
Aim ................................................................................................................................................... 14 
5.4 
Hypothesis ....................................................................................................................................... 14 
5.5 
Objectives ........................................................................................................................................ 14 
5.5.1 
Primary objective ..................................................................................................................... 14 
5.5.2 
Secondary objectives ............................................................................................................... 14 
5.5.3 
Exploratory objectives ............................................................................................................. 15 
5.5.4 
Stratified (subgroup) exploratory objectives ........................................................................... 15 
5.6 
Trial design ....................................................................................................................................... 16 
5.6.1 
Figure 1: Trial design ................................................................................................................ 17 
6 
METHOD ................................................................................................................................................. 17 
6.1 
Study setting .................................................................................................................................... 17 
6.1.1 
Eligibility criteria ...................................................................................................................... 17 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 6 af 65 
 
6.1.2 
Inclusion criteria ...................................................................................................................... 18 
6.1.3 
Exclusion criteria ...................................................................................................................... 18 
6.1.4 
Selection of target hand .......................................................................................................... 20 
6.2 
Study treatments ............................................................................................................................. 20 
6.2.1 
Intervention and placebo ........................................................................................................ 20 
6.2.2 
Concomitant therapies ............................................................................................................ 22 
6.2.3 
Treatment adherence .............................................................................................................. 23 
6.3 
Outcomes ........................................................................................................................................ 23 
6.3.1 
Primary outcome ..................................................................................................................... 23 
6.3.2 
Secondary outcomes ............................................................................................................... 23 
6.3.3 
Exploratory outcomes ............................................................................................................. 23 
6.3.4 
Stratified (subgroup) exploratory outcomes ........................................................................... 24 
6.4 
Measures for descriptive statistics .................................................................................................. 24 
6.5 
Description of efficacy outcome measures ..................................................................................... 25 
6.6 
Description of imaging measures .................................................................................................... 28 
6.6.1 
X-ray ......................................................................................................................................... 28 
6.6.2 
Ultrasound ............................................................................................................................... 28 
6.6.3 
Dual energy CT ......................................................................................................................... 29 
6.6.4 
Cone beam CT .......................................................................................................................... 29 
6.7 
Description of safety outcome measures ........................................................................................ 29 
6.7.1 
Adverse event .......................................................................................................................... 29 
6.7.2 
AE and SAE recording .............................................................................................................. 30 
6.7.3 
Serious adverse events ............................................................................................................ 30 
6.7.4 
Suspected unexpected serious adverse reaction (SUSAR) ...................................................... 31 
6.7.5 
Relationship to study treatment ............................................................................................. 31 
6.7.6 
Participant withdrawal ............................................................................................................ 32 
6.7.7 
Participant discontinuation ..................................................................................................... 32 
6.7.8 
Study discontinuation .............................................................................................................. 32 
6.8 
Participant timeline ......................................................................................................................... 33 
6.8.1 
Table 5: Participant timeline ................................................................................................... 33 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
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6.8.2 
Assessment visit windows ....................................................................................................... 36 
6.8.3 
Recruitment ............................................................................................................................. 36 
6.8.4 
Pre-screening in the outpatient clinic ..................................................................................... 36 
6.8.5 
Telephone pre-screening ......................................................................................................... 37 
6.8.6 
Visit 1: Oral information visit (pre-screening) ......................................................................... 37 
6.8.7 
Visit 2: Screening visit .............................................................................................................. 38 
6.8.8 
Visit 3: Baseline visit ................................................................................................................ 38 
6.8.9 
Visit 4: Week 4 telephone visit ................................................................................................ 39 
6.8.10 
Visit 5: Pregnancy home screening .......................................................................................... 39 
6.8.11 
Visit 6: Week 12 visit................................................................................................................ 39 
6.8.12 
Visit 7: Post-study week 16 ...................................................................................................... 40 
6.8.13 
Visit 8: Pregnancy home screening .......................................................................................... 40 
6.8.14 
Visit 9: Pregnancy home screening .......................................................................................... 40 
6.8.15 
Delegation of study visits......................................................................................................... 40 
6.8.16 
Study completion ..................................................................................................................... 40 
6.8.17 
Protocol violations ................................................................................................................... 41 
6.8.18 
Participant retention and follow-up (drop-outs) ..................................................................... 41 
6.9 
Allocation ......................................................................................................................................... 41 
6.10 
Sample size and power considerations ........................................................................................... 41 
7 
METHODS: Assignment of interventions ................................................................................................ 42 
7.1 
Blinding ............................................................................................................................................ 42 
7.2 
Unblinding ....................................................................................................................................... 42 
8 
METHODS ................................................................................................................................................ 42 
8.1 
Data collections methods ................................................................................................................ 42 
8.2 
Data management ........................................................................................................................... 42 
8.2.1 
Source Documents ................................................................................................................... 43 
8.2.2 
Case Report Forms ................................................................................................................... 43 
8.2.3 
Data management upon completion of data entry ................................................................. 43 
8.2.4 
Data Protection Act and General Data Protection Regulation ................................................ 44 
8.3 
Statistical methods .......................................................................................................................... 44 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
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8.3.1 
Analysis population ................................................................................................................. 44 
8.3.2 
Missing data ............................................................................................................................. 45 
8.3.3 
Primary outcome ..................................................................................................................... 45 
8.3.4 
Secondary outcomes ............................................................................................................... 45 
8.3.5 
Exploratory outcomes ............................................................................................................. 45 
8.3.6 
Statistical analysis plan ............................................................................................................ 46 
9 
RESEARCH ETHICS ................................................................................................................................... 46 
9.1 
Oral information .............................................................................................................................. 46 
9.2 
Written information ........................................................................................................................ 46 
9.3 
Informed consent ............................................................................................................................ 47 
9.4 
Risk associated with the intervention ............................................................................................. 47 
9.4.2 
Colchicine safety in drug-drug interactions ............................................................................. 48 
9.5 
Risk associated with study participation ......................................................................................... 50 
9.5.1 
Questionnaires and physical examination............................................................................... 50 
9.5.2 
Blood samples .......................................................................................................................... 50 
9.5.3 
Radiation safety ....................................................................................................................... 50 
9.6 
Benefit of study participation .......................................................................................................... 51 
9.7 
Insurance ......................................................................................................................................... 51 
9.8 
Health Research Ethical approval .................................................................................................... 51 
10 
PERSPECTIVE ........................................................................................................................................... 51 
11 
PATIENT INVOLVEMENT ......................................................................................................................... 52 
12 
PUBLICATION .......................................................................................................................................... 52 
13 
FUNDING ................................................................................................................................................. 53 
14 
CONFLICT OF INTEREST ........................................................................................................................... 54 
15 
ROLES AND RESPONSIBILITY ................................................................................................................... 54 
16 
APPENDIXES ............................................................................................................................................ 55 
16.1 
Appendix 1: Laboratory samples ..................................................................................................... 55 
16.2 
Appendix 2: Paracetamol and NSAID diary ..................................................................................... 56 
16.3 
Appendix 3: Efficacy outcomes........................................................................................................ 61 
16.4 
Appendix 4: Danish Medicines Agency Product Resumé for tablet colchicine “Tiofarma” ............ 61 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
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16.5 
Appendix 5: Guideline for oral information .................................................................................... 61 
16.6 
Appendix 6: Written information .................................................................................................... 61 
16.7 
Appendix 7: Informed consent form ............................................................................................... 61 
16.8 
Appendix 8: Study participant card ................................................................................................. 61 
17 
REFERENCES ............................................................................................................................................ 61 
 
 
 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
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3 ABBREVIATIONS 
ACR 
American College of Rheumatology  
AE 
Adverse events 
ANCOVA 
Analysis of covariance 
AO 
As-observed 
AUSCAN 
Australian/Canadian hand index score 
Bid 
Bis in die [two times daily] 
CBCT 
Cone-beam computed tomography 
CI 
Confidence interval 
CMC 
Carpometacarpal 
CPP 
Calcium pyrophosphate 
CPPD 
Calcium pyrophosphate deposition 
CRF 
Case Report Form 
CYP3A4 
Cytochrome P450 3A4 
DECT 
Dual-energy computed tomography 
DEI 
Dual Energy Index 
DIP 
Distal interphalangeal  
EQ-5D 
European Quality of Life 5 Dimensions 
EULAR 
European League Against Rheumatism 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice  
HA 
Hydroxyapatite 
HADS 
Hospital Anxiety Depression Scale  
HAQ-DI 
Health Assessment Questionnaire Disability Index 
HOAMRIS 
Hand Osteoarthritis Magnetic Resonance Imaging Scoring System 
HU 
Hounsfield Unit 
IAP 
Image analysis plan 
ICF 
Informed consent form 
ICMJE 
International committee of medical journal editors 
IP 
Interphalangeal 
IPQ 
Illness Perception Questionnaire 
ITT 
Intention-to-treat 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
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KL 
Kellgren Lawrence 
MCP 
Metacarpophalangeal  
MSU 
Monosodium urate 
NSAID 
Non-steroid anti-inflammatory drugs 
OA 
Osteoarthritis 
OARSI 
Osteoarthritis Research Society International 
OMERACT Outcome Measures in Rheumatology 
PIP 
Proximal interphalangeal  
PP 
Per protocol 
PRPs 
Patient research partners 
PsA 
Psoriatic arthritis 
Qd 
Quaque di [once daily] 
PSQI 
Pittsburgh Sleep Quality Index  
RA 
Rheumatoid arthritis 
SAE 
Serious adverse event 
SAR 
Serious adverse reaction 
SD 
Standard deviation 
SPIRIT 
Standard Protocol Items: Recommendations for Interventional Trials 
SUSAR 
Suspected unexpected serious adverse reaction 
US 
Ultrasound 
VAS 
Visual analogue scale 
 
 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
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4 TRIAL IDENTIFIER 
4.1 Full title of trial 
Colchicine treatment for patients with hand osteoarthritis: A randomised, placebo-controlled trial. 
 
4.2 Acronym 
COLOR: COLchicine treatment for patients with hand OsteoaRthritis. 
 
4.3 Short title 
Colchicine vs placebo for hand OA. 
 
4.4 Health Research Ethics Committee Number 
H-20037713  
 
4.5 European clinical trials database (EudraCT number) 
2020-002803-20 
 
4.6 Version number and date 
Version 2, 24.07.2020 
 
4.7 Revision history 
4.7.1 
Table 1: Revision history 
Version 
# 
Issue date 
List of major changes 
1.0 
04.06.2020 
Version for first submission for authority approval 
2.0 
24.07.2020 
At request of the Danish Medicines Agency following changes have been 
made: Complete list of laboratory samples have been added. Elaborate 
information and precautions regarding colchicine related reproductive 
toxicity, including updated guidelines for anti-conceptional therapy in 
exclusion criteria and timely pregnancy screening of female fertile 
participants. Procedure for unblinding. Elaborated receiver control of study 
medication.   

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
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3.0 
24.11.2020 
Stratification was added to the randomisation: age (<75, ≥75), BMI (<30, ≥30), 
gender (male, female) 
 
4.8 Expected timeline 
First patient first visit: September 2020 
Last patient first visit: June 2021 
Last patient last visit: September 2021 
5 INTRODUCTION 
5.1 Background 
Hand osteoarthritis (OA) is a common disease and the prevalence of symptomatic hand OA has been 
estimated to 26.2% among women and 13.4% among men (The Framingham Study) [1]. Incidence increases 
with age and it is more prevalent among women [2]. Pain is the dominant symptom, but swelling and 
stiffness of the joint also occur [3]. It often affects distal interphalangeal (DIP) joints, thumb base and 
proximal interphalangeal (PIP) joints, and is bilateral, symmetrical and polyarticular in most cases [4]. 
Imbalance between on-going repair and destruction leads to characteristic progressive breakdown of 
articular cartilage and remodelling of the underlying bone [5, 6]. Hand OA affects all components of the 
joint and periarticular structures [7]. 
Some patients experience intermittent inflammatory flares [8]. Inflammation is associated with 
development of erosions in the joint [9]. Erosive hand OA can be difficult to distinguish from rheumatoid 
arthritis (RA) and psoriatic arthritis (PsA), however autoimmune features are not present in OA [10-12]. 
Inflammatory reactions in joints with OA could be due to crystal formation [13, 14]. The causal 
relationship is debated [15, 16]. Calcium-containing crystals have been associated with OA [17], and based 
on in-vitro studies [13, 14] it is proposed that crystals may be the initiating component for activation of 
inflammatory pathways [18, 19]. 
Hand OA treatment aims to reduce symptoms and improve function and quality of life [20]. 
Management strategies should be patient-centred and multifactorial, embracing non-pharmacological, 
pharmacological and surgical interventions [20-22]. No therapeutic agent has proven effective in 
preventing, reversing or halting disease progression. 
 
5.2 Rationale and evidence-based research 
Colchicine, a therapeutic agent normally used to treat gout flares, has been trialled for knee OA with 
divergent results: One study found no symptom reduction when examining oral colchicine as the sole 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 14 af 65 
 
treatment for an unselected subgroup of patients with knee OA [23]. Even though the study failed to 
reduce symptoms, a reduction of biomarkers associated with OA severity and progression risk was found. 
Three trials reported symptom reduction, but examined only women [24] or oral colchicine as an add-on 
therapy to a cyclooxygenase inhibitor [25] or intra-articular steroid [26]. Oral colchicine is considered safe 
and well-tolerated, please see section “Risk associated with the intervention” for specifics. To our 
knowledge no previous or planned trials have tested oral colchicine treatment for patients with hand OA. 
As efficacy is unknown, we plan to use placebo as comparator control group. If oral colchicine treatment 
proves effective, further research could consider using other potentially active treatments as comparator.  
 
5.3 Aim 
To compare oral colchicine 0.5 mg administered bid (bis in die [two times daily]) for 12 weeks with placebo 
as a treatment of hand OA symptoms. 
 
5.4 Hypothesis 
We hypothesize that oral colchicine is superior to placebo in reducing pain in patients with hand OA. 
 
5.5 Objectives 
5.5.1 
Primary objective 
To compare the effect of oral colchicine 0.5 mg bid, relative to placebo, on changes in finger joint pain of 
the target hand measured on a visual analogue scale (VAS) from baseline to week 12, in patients with 
painful hand OA. 
 
5.5.2 
Secondary objectives 
To compare the effect of oral colchicine 0.5 mg bid, relative to placebo, from baseline to week 12, in 
patients with painful hand OA on changes in: 
o Function of both hands measured on the AUSCAN Hand Index Score 
o Thumb base pain of the target hand measured on a VAS scale  
o Pain of both hands measured on the Australian/Canadian (AUSCAN) Hand Index Score 
o Joint activity of the target hand measured on physician tender joint count 
o Patient global assessment measured on a VAS scale 
o Quality of life measured on the European Quality of Life 5 Dimensions (EQ-5D) 
o Hand strength of the target hand measured on grippit 
o Treatment response measured on the Outcome Measures in Rheumatology (OMERACT) 
and Osteoarthritis Research Society International (OARSI) responder criteria [27] at week 
12, in patients with painful hand OA. 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
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5.5.3 
Exploratory objectives 
To compare the effect of oral colchicine 0.5 mg bid, relative to placebo, from baseline to week 4, in patients 
with painful hand OA on changes in: 
• 
Finger joint pain of the target hand measured on a VAS scale 
To compare the effect of oral colchicine 0.5 mg bid, relative to placebo, from baseline to week 12, in 
patients with painful hand OA on changes in: 
• 
Stiffness of both hands measured on the AUSCAN Hand Index Score 
• 
Pain, function and stiffness of both hands measured composite on the AUSCAN Hand Index Score 
• 
General physical function measured on the Health Assessment Questionnaire Disability Index (HAQ-
DI) 
• 
Physician global assessment measured on a VAS scale 
• 
Joint activity of the target hand measured on physician swollen joint count 
• 
Fatigue measured on a VAS scale 
• 
Anxiety and depression measured on the Hospital Anxiety Depression Scale (HADS)  
• 
Sleep measured on the Pittsburgh Sleep Quality Index (PSQI)  
• 
Illness perception measured on the brief illness perception questionnaire (IPQ) 
• 
Crystal associated serum compounds: serum urate, serum ionized calcium and serum magnesium 
• 
Serum marker for inflammation measured by C-reactive protein  
• 
Inflammation (yes/no) of the target hand as measured on ultrasound (US) 
To compare the safety of oral colchicine 0.5 mg bid, relative to placebo, from baseline to week 12, in 
patients with painful hand OA on changes in: 
• 
Colchicine related adverse events (AE) measured as the number of AE 
• 
Colchicine related serious adverse events (SAE) measured as the number of SAE 
• 
Withdrawals measured on the number of withdrawals in total and the number of withdrawals due 
to colchicine related AE 
• 
Use of analgesics measured as the use of paracetamol and non-steroid anti-inflammatory drugs 
(NSAID) 
 
5.5.4 
Stratified (subgroup) exploratory objectives 
To examine if oral colchicine 0.5 mg bid for 12 weeks treatment response measured on VAS finger joint 
pain, relative to placebo, differs when stratified by:  
o Presence of active inflammation (yes/no) at baseline as measured on ultrasound  

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
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o Presence of joint associated crystal deposits (yes/no) at baseline measured by dual-energy 
computed tomography (DECT) 
o The type of joint associated crystal (Monosodium urate (MSU)/calcium pyrophosphate 
(CPP)/hydroxyapatite (HA)) at baseline measured by DECT 
o The presence of joint associated crystal (yes/no) measured by cone-beam computed 
tomography (CBCT) 
o The type of joint associated crystal (MSU/CPP/HA) measured by CBCT 
o Presence of joint associated crystal deposits (yes/no) at baseline measured by ultrasound. 
o Body mass index (BMI) 
o Degenerative status measured by CBCT 
o Degenerative status measured by X-ray 
 
5.6 Trial design 
This study is designed as a randomised, placebo-controlled, double-blind trial with two parallel groups and 
a primary endpoint of changes in hand OA pain after 12 weeks measured on VAS finger joint pain. The 
study will include 100 participants. Treatment duration was based on previous studies [23-26]. Participants 
will receive treatment with either oral colchicine 0.5 mg bid or identically appearing placebo bid. The dose 
is the same as in standard gout treatment and previous studies.  
Participants will be seen by a medical doctor (or his/her delegate) at baseline and at week 12. A 
target hand will be selected, corresponding to the hand with most severe OA. When appropriate and 
possible, baseline and outcome measures will be target hand specific. Participants will be contacted by 
telephone by a medical doctor (or his/her delegate) after 4 weeks of treatment to assess AE and treatment 
adherence. The target hand of all participant will be examined using X-ray and will be scanned by US, DECT 
and CBCT at baseline. Only the US imaging modality will be repeated at week 12. Participants will be asked 
to fill out questionnaires at baseline, week 4 and week 12. Laboratory monitoring will be performed at 
baseline and week 12. A post-study telephone visit at week 16 will assess AE, SAE, study drug withdrawal 
symptoms (i.e. symptoms that occur upon abrupt discontinuation of study drug) and general hand OA 
symptoms. Post-study treatment will consist of conventional hand OA treatment, which can be assigned by 
any medical doctor (e.g. the participants general practitioner), including the study investigator or his/her 
delegate. The trial design will examine superiority of oral colchicine vs. placebo. Trial design overview is 
presented in figure 1. 
 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 17 af 65 
 
5.6.1 
Figure 1: Trial design 
 
 
The figure presents the trial design. CT: Computed tomography. Study’s primary endpoint is at 12 weeks.  
 
6 METHOD 
The study protocol adheres to the Standard Protocol Items: Recommendations for Interventional 
Trials (SPIRIT) guideline [28, 29]. The study will be conducted in agreement with the described protocol. 
Any protocol deviation, violation, amendment or alteration will be described in the Statistical Analysis Plan 
(SAP) and final study report.  
   
6.1 Study setting 
The study and radiological examinations will take place at Bispebjerg and Frederiksberg University Hospital, 
Copenhagen, Denmark. 
 
6.1.1 
Eligibility criteria 
Study participants will have a diagnosis of hand OA. Diagnosis will be confirmed by a medical doctor at 
baseline and participants must fulfil the American College of Rheumatology (ACR) criteria for hand OA [3]: 
• 
Hand pain, aching or stiffness on most days the previous 4 weeks 
And at least 3 of the following features: 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 18 af 65 
 
• 
Hard tissue enlargement of ≥2 of the 10 selected joints* 
• 
Hard tissue enlargement of ≥2 of the 10 DIP joints 
• 
Fewer than 3 swollen metacarpophalangeal (MCP) joints 
• 
Deformity of at least 1 of 10 selected joints* 
*The 10 selected joints are the second and third DIP, the second and third PIP, and the first 
carpometacarpal joints of both hands.  
 
6.1.2 
Inclusion criteria 
An individual will be eligible for study participation if he/she meets the following criteria: 
1. Age ≥18 years. 
2. Hand OA according to the ACR criteria above.  
3. Hand OA finger pain: Pain at rest ≥40 mm on VAS (0 to 100 mm range).  
 
6.1.3 
Exclusion criteria 
A participant will be excluded from the study if he/she meets any of the following criteria listed below. 
Some exclusion criteria require a blood sample, please see section “Visit 2: Screening visit”. A complete list 
of blood samples throughout the trial is available in Appendix 1. Known diseases will be based on diagnosis 
registered in the participants health journal. If an exclusion diagnose is suspected necessary diagnostics will 
be performed before inclusion in the study.   
Comorbidities 
1. Other known medical disease that may affect joints, e.g. RA, gout, PsA 
2. Positive anti-cyclic citrullinated peptide (>10 kU/L)  
3. Known cutaneous deposition diseases (e.g. amyloidosis or porphyria).  
4. Known blood dyscrasias and coagulation disorders 
5. Known malignancy (except successfully treated squamous or basal cell skin carcinoma) 
6. Elevated alanine transaminase (>45 U/L females, >70 U/L for males)  
7. Creatinine clearance ≤60 ml/min 
8. Elevated creatine kinase (>210 U/L females, >280 U/L for males) 
9. Known allergies towards the interventions 
10. Drug or alcohol abuse in the last year 
11. Generalised pain syndromes such as fibromyalgia 
12. Current reflux 
13. Current or recurrent diarrhoeal illnesses 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 19 af 65 
 
14. Current abdominal pain 
15. Known peripheral neuropathies 
16. Any other condition or impairment that, in the opinion of the investigator, makes a potential 
participant unsuitable for participation or which obstruct participation, such as e.g. psychiatric 
disorders. 
Medical history 
17. History of hand surgery within 12 months prior enrolment. 
18. History of arthroplasty or arthrodesis in the hand 
Management strategies 
19. Treatment with P-glycoprotein inhibitors and/or cytochrome P450 3A4 (CYP3A4) inhibitors, see 
section “Colchicine safety in drug-drug interactions” and table 7. If potential participants have been 
treated with these pharmaceuticals previously, treatment must be terminated 5 half-lifes before 
initiation of study drug.   
20. Use of systemic corticosteroids equivalent of ≥ 7.5 mg prednisolone daily within 3 months. 
21. Participation in experimental device or experimental drug study 3 months prior to enrolment.  
22. Intra-articular treatments or aspirations of any kind of any joint in the hands 3 months before 
inclusion 
23.  Intra-articular corticosteroids into any joint 1 months before inclusion 
24. Current use of synthetic or non-synthetic opioids  
25. Scheduled surgery during study participation 
26. Planning to start other treatment for hand OA in the study participation period.    
Reproductive system 
27. Pregnancy. 
28. Planned pregnancy within the study period, 3 months after end of study treatment for female 
fertile participant and 6 months after end of study treatment for male participant.  
29. Insufficient anti-conception therapy for female fertile participants within the study period and 3 
months after end of study treatment. Sufficient anti-conception therapy consists of intra-uterine 
device (coil),hormonal anti-conception (birth control pills, implant, intra-uterine system, dermal 
patch, vaginal ring, or injections) or sexual abstinence Female participants are considered infertile if 
they are postmenopausal or if they have undergone surgical sterilisation (bilateral salpingectomy, 
hysterectomy or bilateral oophorectomy). Postmenopausal state is defined as no menses for 12 
months without alternative medical cause before inclusion in the study. Menopause state will be 
confirmed by measurement of follicle stimulating hormone. 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 20 af 65 
 
30. Insufficient anti-conception therapy for male participants within the study period and 6 months 
after end of study treatment. Sufficient anti-conception therapy consists of condom or sexual 
abstinence. Male participants are considered sterile if they have undergone surgical sterilisation 
(vasectomy).     
31. Breast-feeding 
 
6.1.4 
Selection of target hand 
A target hand will be selected for outcome assessment. Selection of the target hand will adhere to the 
following, with advancement to next step if unable to choose target hand based on the given criteria. 
1. The hand with most overall pain, assessed by VAS finger joint pain. 
2. The hand with most overall reduced function, assessed by AUSCAN function subscale. 
3. The hand with most overall stiffness, assessed by AUSCAN stiffness subscale. 
4. The hand with most swollen joints, assessed by physician joint count. 
5. The hand with most tender joints, assessed by physician joint count. 
6. The hand with highest summed radiographic score, assessed by radiographic scoring of 
conventional X-ray. 
7. If unable to select target hand based on the above criteria, a target hand will be randomly assigned.   
Target hand will be registered in the Case Report Form (CRF). 
 
6.2 Study treatments 
6.2.1 
Intervention and placebo 
Participants in the intervention group will receive 0.5 mg tablets of colchicine. Participants in the placebo 
group will receive placebo tablet. As it was not possible to ensure identical tablets, tablets are packed in 
identical capsules, ensuring blinding, see figure 2. The capsules are made from bovine gelatine and are 
halal. Capsules are to be administered orally bid: morning and evening, no specific time-slots are advised. 
The intervention tablets are commercially available Colchicine “Tiofarma”. The Colchicine “Tiofarma” tablet 
is round, flat, off-white, diameter 6 mm, height 3 mm, and the text “0,5” is printed on one side. The 
placebo tablet consists of lactose monohydrate 50 mg, potato starch 45 mg, magnesium stearate 0.5 mg, 
and talc 4.5 mg, it is round, flat, off-white, diameter 6 mm, height approximately 2 mm, and no text printed 
on it. Medication including packing will be provided by the central pharmacy of the capital region. The 
etiquette on the study medication container will contain a treatment number which the participant will be 
assigned upon randomisation, see figure 3. Each package will contain 56 tablets, and each participant will 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 21 af 65 
 
be provided with 3 packages corresponding to 168 tablets in total. Medication will be sent from the Central 
Pharmacy of the capital region to the Parker Institute by transportation following the standard for 
shipment of medication from the Central Pharmacy of the capital region to the hospitals. Standard 
shipment from the Central Pharmacy follows a validated supply chain and is therefore not  temperature 
logged during transportation. Medication will be received by GCP-trained personal at the Parker Institute. 
Receiver control will contain following assessment: Date [dd.mm.yyyy], is the received medication in 
agreement with the ordered (yes/no), are the packing intact (yes/no), is there any sign of damage (yes/no), 
batch no., name of receiving personal, signature of receiving personal. The assessment sheet will be stored 
for documentation.Medicine will be stored in a locked room destined for medicine. Study medication will 
be placed separately from other medicine. Storing will adhere to recommended storing condition at the 
etiquette i.e. at room temperature not exceeding 25oC. The participant will receive treatment for the entire 
study period upon randomisation, distribution of medicine to participants will be documented. At week 12 
participants will be requested to return unused medication, which also will be documented. Returned 
medication will be stored at the Parker Institute in a locked room, separately from unused medication. 
Once the last participant has attended his/her week 12 visit the returned study medication will be sent with 
courier to the central pharmacy of the capital region where it will be destroyed in agreement the 
pharmacy’s standard procedure. The central pharmacy of the capital region provides receipt for both 
receiving and sending medication, which will be kept for documentation. 
 
6.2.1.1 
Figure 2: Study treatment 
 
A: Commercial colchicine tablet [Colchicin “Tiofarma”]. B: Placebo tablet. C: Capsule in which all study 
medication is packed.  
 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 22 af 65 
 
6.2.1.2 
Figure 3: Study treatment etiquette 
 
 
6.2.2 
Concomitant therapies  
Non-pharmacological interventions are allowed if use is stable for the 3 months prior to enrolment and will 
remain stable until the week 12 visit. Participants are not allowed to start a new non-pharmacological 
intervention aimed at the upper extremities and cervical spine until the week 12 visit has been reached. 
The following therapies will be allowed as concomitant OA therapies during the trial, if a stable dosage 
has been used for 3 months prior to enrolment, and a stable dosage will continue until the week 12 visit: 
• 
Chondroitin sulphate (oral administration) 
• 
Glucosamine (oral administration) 
• 
Bisphosphonate (oral administration) 
• 
Capsaicin (topical administration) 
Concomitant therapies will be recorded at baseline.  
 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 23 af 65 
 
Participants are permitted to remain on their baseline paracetamol (oral administration) and non-steroid 
anti-inflammatory drugs (NSAID) (oral or topical administration) if a stable dose has been used 14 days 
prior enrolment. We will request participants to pause paracetamol and NSAID 24 hours before study visits 
3, 4 and 6. Participants are not allowed to initiate other medical treatment for OA pain, e.g. opioids, 
immunomodulating therapy, joint arthrocentesis, or injections. Surgical treatments of the hands are not 
allowed during study participation.  
 
6.2.3 
Treatment adherence 
Adherence will be registered in the CRF. Participants will be asked about treatment adherence at week 4 
and week 12. 
• 
Participant reported adherence: Study drug used bid, study drug used between bid and qd (quaque 
di [once daily]), study drug used qd, study drug used less than qd, study drug not used.   
Participants will be requested to return excess medication and tablets will be counted at week 12. The 
number of tablets returned will be registered.  
 
6.3 Outcomes 
6.3.1 
Primary outcome 
Change from baseline in VAS finger joint pain of the target hand at week 12 
 
6.3.2 
 Secondary outcomes 
Secondary outcomes are change from baseline to week 12 in: 
• 
Physical function of both hands assessed by AUSCAN physical function subscale 
• 
VAS thumb base pain of the target hand 
• 
Pain of both hands assessed by AUSCAN hand pain subscale 
• 
Joint activity of the target hand assessed by physician tender joint count in the target hand 
• 
VAS patient global assessment 
• 
Quality of life assessed by the EQ-5D 
• 
Hand strength of the target hand assessed by grippit 
• 
Fulfilment of OMERACT-OARSI responder criteria [27] 
 
6.3.3 
Exploratory outcomes 
Change from baseline in 
• 
VAS finger joint pain of the target hand at week 4 
• 
Stiffness of both hands assessed by AUSCAN stiffness subscale at week 12 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 24 af 65 
 
• 
Hand OA symptoms of both hands assessed by the total AUSCAN score at week 12 
• 
Physical function of both hands assessed by the HAQ-DI at week 12 
• 
VAS physician global assessment at week 12 
• 
Physician swollen joint count of the target hand at week 12 
• 
VAS fatigue at week 12 
• 
Risk of anxiety and depression assessed by HADS at week 12 
• 
Sleep quality assessed by PSQI at week 12 
• 
Illness perception assessed by the brief IPQ at week 12 
• 
Serum urate level at week 12 
• 
Serum ionized calcium level at week 12 
• 
Serum magnesium level at week 12 
• 
C-reactive protein level at week 12 
All safety outcomes are considered as exploratory outcomes 
• 
Occurrence of colchicine related AE at week 12 
• 
Occurrence of colchicine related SAEs at week 12 
• 
Withdrawals from the study (regardless of reason) at week 12 
• 
Withdrawals due to colchicine related AEs at week 12 
• 
Use of oral paracetamol and NSAID will be recorded from baseline to week 12 daily by a participant 
diary, see appendix 2. 
 
6.3.4 
Stratified (subgroup) exploratory outcomes 
• 
Change from baseline in inflammations as evaluated by US synovitis score at week 12 
• 
MSU, CPP and HA (yes/no) detected by US at baseline 
• 
MSU, CPP and HA (yes/no) detected by DECT at baseline 
• 
MSU, CPP and HA (yes/no) detected by CBCT at baseline 
• 
Height and weight at baseline 
• 
Degenerative status detected by CBCT 
• 
Degenerative status detected by X-ray 
 
6.4 Measures for descriptive statistics 
For descriptive statistics we will collect medical and surgical history, comorbidities, concomitant therapy 
and co-medication (i.e. current treatments with indications other than OA). Information will be collected 
primarily by interviewing the patient. Electronic health journal and electronic medicinal chart will be 
assessed for additional information by using the participants unique personal identity number (CPR-
number). 
 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 25 af 65 
 
We will collect the following information: 
• 
Age [years] 
• 
Sex (male/female) 
• 
Dominant hand (left/right/ambidextrous) 
• 
OA specific 
o Hand OA symptom duration [year] 
o Joint pain at other sites (yes/no), if yes specify location: neck, shoulder, elbow, wrist, upper 
back, lower back, hip, knee, ankle, feet, other. 
o Known OA at other sites identified from medical records (yes/no), if yes: knee OA, hip OA, 
other OA (specify in text). 
• 
Medical and surgical history, both current and previous: Diagnosis, debut [dd.mm.yyyy], ended 
[dd.mm.yyyy], ongoing (yes/no). 
• 
Menopausal state (pre-menopause/menopause/post-menopause/not relevant) 
• 
Medication: Name, form (e.g. tablet or mixture), route of administration, dose, frequency, 
indication (diagnose), treatment start [dd.mm.yyyy], treatment terminated [dd.mm.yyyy], ongoing 
(yes/no). 
Information will be registered in the CRF. For descriptive statistics hand photos of both hands will be taken. 
For the hand photo hands will be positioned on a horizontal surface, palms down, relaxed, fingers apart. 
Hands will be positioned side-by-side.  
 
6.5 Description of efficacy outcome measures 
All questionnaires and scoring sheets are available in appendix 3. At baseline (visit 3) and 12 week (visit 6) 
data will be collected via touchscreens in the clinic using Cirkeline, see section “Case Report Forms.” 
Questionnaires at the telephone visit (week 4) will be collected using RedCap, see section “Visit 4: Week 4 
telephone visit”. 
  
6.5.1.1 
VAS 
VAS will be used for scoring of pain, fatigue, physician global assessment and patient global assessment. 
The scale spans from 0 to 100, where 0 equals no symptoms and 100 equals worst imaginable symptoms. 
Recall period is 1 week, thus participants will be asked to score average symptoms within the last week. 
Pain will be assessed separately for finger joints and thumb base. For finger joint pain participants will be 
asked to score the average pain in the 2nd to 5th finger joints. For thumb base pain participants will be 
asked to score the average pain in at the thumb base. Participant will be asked to score both finger joint 
and thumb base pain in the target hand and the non-target hand. The remainder of the VAS scores are not 
hand specific but aimed at overall measures. For fatigue participants will be asked to score average fatigue. 
For patient global assessment, participant will be asked to score average general health. Physician global 
assessment does not have a recall period, but is based on experience of health in general, physicians will be 
asked to score general health.    

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 26 af 65 
 
 
6.5.1.2 
AUSCAN 
The Australian/Canadian hand OA index AUSCAN, is a validated questionnaire with 3 subscales assessing 
pain, hand stiffness and hand function during the last 48 hours [30, 31]. The AUSCAN questionnaire is not a 
target hand specific measures but addresses both hands. Validation is limited by focus on right hand 
dominant individuals [32]. It will be available as an appendix for application to Health Research Ethics 
Committee, but not for publication as it is copyrighted, for further information go to www.womac.com. 
AUSCAN comes in both Likert and a visual analogue scale format, and this study uses the visual analogue 
scaled format. 
 
6.5.1.3 
HAQ-DI 
HAQ-DI assesses the difficulty associated with performing everyday activities, recall period is 1 week. 
Questions are rated on a scale of 0-3. A validated Danish translation is available [33]. HAQ-DI is not a hand 
specific measure.  
 
6.5.1.4 
Quality of life 
EQ-5D is a standardised patient-reported instrument for use as a measure of health outcome and quality of 
life, thus it is not a hand specific measure. EQ-5D is designed for self-completion by respondents and is 
ideally suited for use in surveys [34]. The EQ-5D consists of 2 pages – the EQ-5D-3L descriptive system (page 
1) and the EQ Visual Analogue scale (EQ VAS) (page 2). The descriptive system comprises 5 dimensions 
(mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Standardized answer options 
are given (3 Likert boxes) and each question is assigned a score from 1 to 3. It is simple, taking only a few 
minutes to complete. Instructions to respondents are included in the questionnaire. The EQ VAS records 
the respondent’s self-rated health on a 20 cm vertical, visual analogue scale with endpoints labelled ‘the 
best health you can imagine’ and ‘the worst health you can imagine’. This information can be used as a 
quantitative measure of health as judged by the individual respondents. A Danish version of the EQ-5D is 
available and a Danish valuation set for reference is also available [35].  
 
6.5.1.5 
Joint count 
Joint assessment includes bilateral examination of the first carpometacarpal (CMC-1) and first 
interphalangeal (IP) joints as well as second to fifth MCP, PIP and DIP joints. Joints will be assessed by the 
investigator or his/her delegate for swelling and tenderness according to the European League Against 
Rheumatism (EULAR) handbook [36] in a dichotomous manner. Both hands will be scored.   
 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 27 af 65 
 
6.5.1.6 
Grip strength  
Changes in the hand function are associated with changes in grip strength [37]. Grip strength 
measurements provide objective data on the muscular performance of the hand. Grip strength is assessed 
using the Grippit instrument that records grip force in Newtons. Three measurements are performed on 
each hand and averaged separately for each hand. 
 
6.5.1.7 
OMERACT-OARSI responder criteria 
To assess treatment response, the validated OMERACT-OARSI criteria will be applied [27]. The criteria 
combine target hand specific measures with measurement that apply to both hands.   
Participants will be classified as a responder if: 
1. the relative change in VAS finger joint pain of the target hand or AUSCAN function of both hands is 
≥ 50% and the absolute change is ≥ 20; or 
2. at least 2 of the following applies: 
a. the relative change in VAS finger joint pain of the target hand is ≥ 20% and the absolute 
change is ≥ 10. 
b. the relative change in AUSCAN function of both hands is ≥ 20% and the absolute change ≥ 
10. 
c. the relative change in VAS patient global assessment is ≥ 20% and the absolute change ≥ 
10. 
The absolute change is equal to the change from baseline to week 12. The relative change is the absolute 
change divided by the baseline score.  
 
6.5.1.8 
HADS 
HADS consists of two subscales with seven questions concerning anxiety and seven questions concerning 
depression [38]. The recall period is 1 week. The tool aims to help distinguish physical illness from mental, 
and can also assess symptom severity [39]. Each item is scored on a 0-3 scale. A cut-off value of 8 on each 
subscale suggest possible illness [39]. A Danish version of the questionnaire is available and have been 
validated among cardiac patients [40]. HADS is not a hand specific measure. 
 
6.5.1.9 
PSQI 
PSQI consist of 11 items, two of which contain multiple sub-questions [41]. In the PSQI scoring the 
questions are pooled into 7 components: subjective sleep quality, sleep latency, sleep duration, sleep 
efficiency, sleep disturbance, use of sleep medication, and daytime dysfunction. Each component is scored 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 28 af 65 
 
on a 0-3 scale providing a total score of 0-21. Higher scores indicate worse sleep quality. The Danish 
translation is limited by lack of validation. PSQI is not a target hand specific measure. 
 
6.5.1.10 Brief IPQ 
The brief IPQ is a scale assessing cognitive and emotional representation of illness. It is reliable and valid 
when compared to relevant measures. It contains eight numerical rating scale questions that each assess 
one dimension of illness perception and a memo field based on patients’ own beliefs about their condition. 
Dimensions are scored separately (1–10) [42]. The Danish translation is limited by lack of validation. Brief 
IPQ is not a hand specific measure. 
 
6.6 Description of imaging measures 
6.6.1 
X-ray 
Existing hand radiographs will be used in case these are not longer than 6 months old at the time of the 
screening visit. If there are no existing hand radiographs these will be obtained for both hands in a standard 
anterior-posterior projection at the Department of Radiology  X-ray’s will be used to describe degenerative 
status, image scoring will be described in a the SAP or the image analysis plan (IAP).  
 
6.6.2 
Ultrasound 
Ultrasound (US) examinations will be performed with a Logiq E10 using a 15 MHz linear transducer. US-
examinations will be performed by Karen Ellegaard (KE), who has more than 15 years of experience in 
musculoskeletal US. The US pre-set will be fixed during the study. The grey scale will be optimized for 
detection of signs of crystal deposits and only the gain and focus can be adjusted in order to optimize the 
image. The Doppler settings will be optimized for detection of slow flow [43]. Only the target hand will be 
assessed with US. The joints assessed will be DIP and PIP 2-5, IP-1, MCP 1-5 and CMC-1. The joints will be 
scanned both from the volar and dorsal aspect with the hand lying relaxed on the examination table. The 
joints will be scanned in the longitudinal plane and the transverse plane will be used to confirm abnormal 
findings. 
In the US examination at baseline will address crystal deposits (yes/no), inflammation and bony changes.  
US examination at week 12 will only assess inflammation. Scoring will be described in the SAP or the IAP. 
US findings will be registered in the CRF. US stills will be used to document findings and re-score images.  
 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 29 af 65 
 
6.6.3 
Dual energy CT  
Target hand will be examined with a dual-source dual-energy CT scanner (Siemens Somatom Force, 
Siemens Healthineers, Forchheim, Germany). Data acquisition settings and image reconstruction 
parameters are presented in table 2, Sn indicates use of a Tin filter to increase the spectral separation. Dual 
energy CT image reading will score for crystal deposits (yes/no) and crystal characterisation (MSU/CPP/HA). 
Software will be calibrated to crystal detection by scanning several crystal calibration phantoms at different 
known crystal concentrations. Image reading will be described in the SAP or IAP. 
Table 2: Dual-energy computed tomography data acquisition and image reconstruction parameters  
Scanner 
Force 
Tube voltage combination 80/sn150 kV 
Collimation 
64 x 0.6 mm 
CTDi 
8 mGy 
Rotation 
0.5 
Pitch 
0.3 
CT image Slice thickness 
0.5 mm 
CT image voxel size 
0.325 x 0.325 mm2 
CTDi: Computed tomography dose index. CT: Computed tomography. Sn: Tin filter.  
 
6.6.4 
Cone beam CT 
Non-contrast CBCT of the target hand will be performed in all participants on a Carestream OnSight® 
scanner. The CBCT scanner can perform a 3-dimensional scan of the target joint by rotating three X-ray 
emitting tubes 270 degrees around the anatomy of interest in approx. 20-25 seconds. CBCT has the 
advantage of low dose and very high resolution (isotropic voxel size less than 0.3 mm). Software will be 
calibrated to crystal detection by scanning several crystal calibration phantoms at different known crystal 
concentrations. CBCT will be used to score degenerative status and crystal depositions (yes/no) and crystal 
characterization (MSU/CPP/HA). Scoring will be described in the SAP or IAP. 
 
6.7 Description of safety outcome measures 
6.7.1 
Adverse event 
An AE will be defined by any untoward medical occurrence, any unfavourable and unintended sign, 
symptom, or disease. Worsening of a pre-existing condition will also be considered an AE. AE will be 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 30 af 65 
 
registered regardless of any causal relationship to the allocated treatment. Any AE with onset or worsening 
reported by a participant during the study period will be considered a treatment emergent AE.  
AE will be rated by severity, see table 3. 
Table 3: AE severity  
Mild 
Transient AE easily tolerated by the participant 
Moderate AE leading to participant discomfort and interrupt the participant’s usual activities. 
Severe 
AE leading to considerable interference with the participant’s usual activities and may be 
incapacitating or life-threatening. 
Known AEs related to the intervention are described in table 6. Laboratory monitoring at visit 6 will be used 
to assess hepatotoxicity (alanine transaminase [U/L]), bone marrow depression (haemoglobin [mM], 
thrombocytes [*109/L], differentiated leucocytes [*109/L]), rhabdomyolysis (creatine kinase [U/L]), and 
reduced kidney function (creatine clearance [mL/min], potassium [mM], and sodium [mM]). A complete list 
of blood samples throughout the trial is available in Appendix 1. Blood will be sampled and analysed at the 
central laboratory at Bispebjerg and Frederiksberg Hospital and destroyed after evaluation according to 
standard clinical procedures, thus blood will not be stored in a biobank. Approximately 20-25mL of blood 
will be drawn. Laboratory results will be available to the physician in charge in the patient health file 
(Sundhedsplatformen) immediately upon analyses and will be reviewed for abnormal findings.   
 
6.7.2 
AE and SAE recording 
The investigator will assess and record any AE in detail including the date of onset, description, severity, 
duration and outcome, and any action(s) taken. Relationship of the AE to study treatment will be rated as 
described in section “Relationship to study treatment”.  
AE registration will start at baseline and continue post-study to week 16. AE will be recorded at week 4, 
week 12 and week 16. The participant can report an AE during the study period by contacting the 
investigator site by telephone.  
All AE will be followed until they have abated, or until a stable situation has been reached.  
AEs will be registered in the CRF.  
 
6.7.3 
Serious adverse events 
Any AE meeting the following criteria are considered serious: 
• 
Results in death 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 31 af 65 
 
• 
Is life-threatening, i.e. any event in which the patient was at the risk of death at the time of the 
event. Events that hypothetically might have caused death if it was more severe is not covered by 
the term.  
• 
Requires inpatient hospitalization or prolongation of existing hospitalization 
• 
Results in persistent or significant disability/incapacity 
• 
Is a congenital anomaly/birth defect. 
All SAE should be reported to sponsor as quickly as possible, and within 24 hours after the investigator (or 
his/her delegate) have been made aware of the incidence. Investigator (or his/her delegate) will evaluate 
whether the SAE is a serious adverse reaction (SAR), see next section. Sponsor will evaluate whether the 
SAE is a SAR and optionally a suspected unexpected serious adverse reaction (SUSAR), see next section. 
Once a year in the entire study period the sponsor will provide a list of SAR and general evaluation of safety 
in the study, that will be sent to Danish Medicines Agency and the Health Research Ethics Committee.  
 
6.7.4 
Suspected unexpected serious adverse reaction (SUSAR) 
A SAR can be a SUSAR, which means that it is unexpected, as it is not consistent with current information. If 
the sponsor judge that a SAE is SUSAR he is responsible for reporting it to the Danish Medicines Agency and 
the local Health Research Ethics Committee. A SUSAR that is life-threatening must be reported to the 
national competence authority within 7 days (15 days in case of non life-threatening SUSAR). 
 
6.7.5 
Relationship to study treatment 
All AE, SAE, SAR, SUSARs will be registered whether the event is known or unknown, reference will be the 
Danish Medicines Agency product resumé for tablet colchicine “Tiofarma” section 4.8, see appendix 4. 
AE will be rated to study treatment in one of three groups, see table 4. 
Table 4: Relationship of AE to study treatment 
Probably 
related 
An AE has a strong temporal relationship to study treatments or recurs on re-challenge 
and an alternate aetiology is unlikely or significantly less likely.  
Probably not 
related 
An AE has little or no temporal relationship to the study treatments and/or a more likely 
alternative aetiology exists. 
Not related 
An AE is due to an underlying or concurrent illness or effect of another exposure and is 
not related to the study treatments (e.g., has no temporal relationship to study 
treatments or has a much more likely alternative aetiology). 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 32 af 65 
 
If the first category is not chosen, an alternative aetiology must be provided by the investigator for the AE. 
Evaluation of relationship to study treatment must bear known side-effects in mind, see section “Risk 
associated with the intervention”. 
 
6.7.6 
Participant withdrawal  
Participants are free to withdraw from the trial at any time without reason. Withdrawal will not have any 
consequences for the participant in future investigations and/or treatments at the site. Withdrawn 
participants will not be replaced. Decision to withdraw can come from the participant or from the 
investigator in case of urgent medical reasons or SAE. Participants who withdraw from treatment will be 
requested to participate in week 4, week 12,  week 16, week 20 and week 24 visits and efficacy assessment 
to minimize missing data.   
 
6.7.7 
Participant discontinuation 
The investigator may discontinue the participant for any reason. Participants will be discontinued if any of 
the following occur 
• 
Clinically significant AEs, which rule out continuation of the study treatment, as determined by the 
investigator. 
• 
Other illness, which rule out continuation of the study treatment, as determined by the 
investigator. 
If at any point in time between randomisation and week 12 the investigator feels that the participant’s 
clinical course is not acceptable within the normally applied paradigms of hand OA, the participant will be 
requested to withdraw from treatment, and it will be evaluated whether the participant should be taken 
out of the study completely. The clinician’s judgment will be required to decide on a case-by-case basis 
whether to implement this step or not. 
 
6.7.8 
Study discontinuation 
The study can be terminated at any time if the incidence of AE in this or other studies indicate a potential 
health hazard to the participants. 
 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 33 af 65 
 
6.8 Participant timeline 
Participant timeline and study procedures are evident from table 5 below. 
6.8.1 
Table 5: Participant timeline 
Study phase 
Pre-
screening Screening Baseline Week 4 
 
 
Week 8 
Primary 
endpoint, 
week 12 
Post-
study, 
week 16 
Post-
study, 
week 20 
Post-
study, 
week 24 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
Days 
≥ -7 
-35 to -7 
-7 to 0 
21 to 35 
49-63 
77-84 
105-119 134-148 162-176 
Oral information 
x 
  
  
  
 
  
  
 
 
Written information 
x 
 
 
 
 
 
 
 
 
Eligibility assessment 
 
x 
 
 
 
 
 
 
 
Selection of target hand 
 
x 
 
 
 
 
 
 
 
Informed consent 
  
x 
  
  
 
  
  
 
 
Randomisation 
  
  
x 
  
 
  
  
 
 
Medical history [1] 
  
x 
x 
x 
 
x 
x 
 
 
Treatment 
 
 
 
 
 
 
 
 
 
• 
Colchicine 
 
 
x ----- ----------- ----------- -------x 
 
 
 
• 
Placebo 
 
 
x ----- ----------- ----------- -------x 
 
 
 
Patient reported outcomes 
  
  
  
  
 
  
  
 
 
• 
VAS finger joint 
pain scoring 
  
  
x 
x 
 
x 
  
 
 
• 
VAS thumb base 
pain scoring 
  
  
x 
x 
 
x 
  
 
 
• 
AUSCAN 
  
  
x 
x 
 
x 
  
 
 
• 
HAQ-DI 
 
 
x 
x 
 
x 
 
 
 
• 
EQ-5D  
  
  
x 
x 
 
x 
  
 
 
• 
VAS fatigue 
  
  
x 
x 
 
x 
  
 
 
• 
VAS patient global 
assessment 
  
  
x 
x 
 
x 
  
 
 
• 
HADS  
  
  
x 
  
 
x 
  
 
 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 34 af 65 
 
• 
PSQI 
  
  
x 
  
 
x 
  
 
 
• 
Brief IPQ 
 
 
x 
 
 
x 
 
 
 
• 
Joint count 
 
 
x 
 
 
x 
 
 
 
Other examinations 
  
  
  
  
 
  
  
 
 
• 
Weight 
  
  
x 
  
 
  
  
 
 
• 
Height 
  
  
x 
  
 
  
  
 
 
• 
Blood pressure 
  
  
x 
  
 
x 
  
 
 
• 
Physical 
examination 
  
x 
x 
  
 
x 
  
 
 
• 
Grip strength [2] 
  
  
x 
  
 
x 
  
 
 
• 
VAS physician 
global assessment 
  
  
x 
  
 
x 
  
 
 
Ultrasound 
  
  
x 
  
 
x 
  
 
 
X-ray [3] 
  
x 
  
  
 
  
  
 
 
Dual-Energy CT 
  
  
x 
  
 
  
  
 
 
Cone-beam CT 
  
  
x 
  
 
  
  
 
 
Laboratory monitoring [4] 
  
x 
  
  
 
x 
  
 
 
Safety recording [5] 
  
  
  
x 
 
x 
x 
 
 
Pregnancy screening [6] 
 
 
 
 
 
 
 
 
 
• 
Blood sample 
 
x 
 
 
 
x 
 
 
 
• 
Urine test 
 
 
x 
x 
x 
 
x 
x 
x 
Assessment of treatment 
adherence  
  
  
  
x 
 
x 
  
 
 
Day 0 refers to the day study treatment is initiated.  
1: Includes outcomes specified in section “Outcomes for descriptive statistics”. Medical history is obtained at each visit and will be updated to adjust 
for any new events or treatments. At the post-study week 16 visit medical history will focus on study drug withdrawal symptoms and general hand-OA 
symptoms. 
2: Measured on Grippit [Newtons]. 
3: Existing hand radiographs will be used in case these are not longer than 6 months old. 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 35 af 65 
 
4: A complete list of blood samples throughout the trial is available in Appendix 1. 
5: AE, SAE, discontinuation of study drug, initiation of rescue treatment. 
VAS: Visual analog scale (0-100 mm). AUSCAN: Australian/Canadian Osteoarthritis Hand Index pain, disability, and stiffness subscales. HAQ-DI: Health 
Assessment Questionnaire Disability Index. EQ-5D: European Quality of Life 5 Dimensions. HADS: Hospital Anxiety Depression Scale. PSQI: Pittsburgh 
Sleep Quality Index. IPQ: Illness Perception Questionnaire. CT: Computed tomography.      
6: Only for female fertile participant. Urine screening will be done at home at visit 4, 5 and 8, and reported to the investigator or his/her delegate using 
telephone or email. 
 
 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 36 af 65 
 
6.8.2 
Assessment visit windows 
Visit 1 will be performed at least 1 week prior initiation of treatment, corresponding to day ≥ -7. Visit 2 will 
be performed 1 to 5 weeks before initiation of treatment, corresponding to day -35 to -7. Visit 1 and visit 2 
may take place on the same day. Visit 3 will be performed within a timeframe of 1 week prior initiation of 
treatment, corresponding to day -7 to 0. Visit 4, 5, 7 and 8 will be performed within +/- 1 week (7 days) for 
the scheduled visit. Visit 6 will be performed within a timeframe of 1 week before primary endpoint, 
corresponding to day 77-84.  
 
6.8.3 
Recruitment 
Participants will be recruited from the Parker Institutes outpatient OA clinic. Patients who are followed at 
the clinic and known to have hand OA will be invited to participate in the trial. Please see section below on 
pre-screening in the outpatient clinic. 
If further recruiting is required, we will place an advert in the local free-of-charge newspaper 
MetroXpress. Please see section on telephone pre-screening. 
 
6.8.4 
Pre-screening in the outpatient clinic 
The number of individuals pre-screened in the OA outpatient clinic will be registered. For individuals not 
proceeding to screening, the reason for drop-out will be registered. 
Potential trial participants will be identified by the investigator in the outpatient 
osteoarthritis clinical at Bispebjerg Frederiksberg Hospital. The identification of potential participants may 
occur during regular clinical visits. 
When a potential trial participant is identified by an investigator or a treating medical doctor 
in the clinic, a brief oral information about the trial is provided and the written information material will be 
handed out.  
If the potential participant is identified by a medical doctor that is not an investigator of the 
current trial, the potential participant will be asked if he/she accepts that his/her information is transferred 
to an investigator, so the investigator can initiate contact with the potential participant. The information 
that will be transferred will be restricted to: 
• 
Name 
• 
CPR-number 
• 
Contact information (telephone, email, postal address) 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 37 af 65 
 
Furthermore, the potential participant is asked if he/she wishes to schedule an appointment for the oral 
information visit and/or a screening visit. It must be ensured that the potential participant is provided an 
opportunity to have at least 24 hours of reflection time before the screening visits. 
Patient in the out-patient clinic who may be eligible for the study can also be contacted by the 
investigator or his/her delegate by telephone, see next section.  
 
6.8.5 
Telephone pre-screening 
Advertisements will encourage potentially eligible individuals to contact the Parker Institute secretariat via 
telephone for further information and scheduling of an oral information visit and a screening visit upon 
answers to a few simple questions regarding key eligibility criteria.  
 
The written information material will be sent by e-boks (national secure postal service) to the potential trial 
participant and the scheduling of a screening visit will ensure that he or she is provided with an opportunity 
to have at least 24 hours of reflection time (to read the material) before the oral information visit. 
 
6.8.6 
Visit 1: Oral information visit (pre-screening) 
The oral information visit will be organised as an individual session with the investigator (or his/her 
delegate) in the out-patients clinic. Potential participants have the right to bring next of kin or another 
person of the participant’s choice with him/her to the oral information visit. 
The following will be emphasized: 
• 
Participation in the trial is voluntary. 
• 
Participants have the right to minimum 24 hours reflection time before deciding to sign the 
informed consent or not.  
• 
Participants can at any time and without giving any reason, withdraw from the trial without 
affecting the potential participant’s right to current or future treatment.   
 
Further, the oral information will include: aim, procedures, potential benefits and risks when participating 
in the trial, procedures for random findings during the project, procedures for securing the participants 
privacy and data protection, information on the trial organisation, funding, as well as contact information 
on the primary investigator and other key investigators. 
The investigator will make sure that participants have received and understood the 
information given to them. The investigator will make sure they are aware that they have the right to 
minimum 24 hours reflection time before signing the informed consent. 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 38 af 65 
 
The written information material will be provided. 
If participant decline the right to 24 hours reflection, visit 2 can take place immediately after 
visit 1 on the same day.  
 
6.8.7 
Visit 2: Screening visit 
Potential participants will be requested to refrain from food and drinks 10 hours before visit 2 in order to 
ensure fasting blood sample, water intake is accepted within the fasting period. At the screening visit the 
following procedures will be done in this order. Signed informed consent is necessary to proceed to the 
following steps.  
1. Provision of signed informed consent 
2. Assessment of in- and exclusion criteria. 
3. Registration of background information, see section “Outcomes for descriptive statistics” 
4. Physical examination: 
• 
Heart and lung auscultation 
• 
Joint examination, see section “Joint count”.  
3. Laboratory test: Blood sample, cf. exclusion criteria and parameters for exploratory outcome. For 
fertile female participants, this will also include pregnancy screening. A complete list of blood 
samples throughout the trial is available in Appendix 1. Parameters ≤ 1 week old need not be 
repeated, except anti-cyclic citrullinated peptide, were measures ≤ 1 year old need not be 
repeated.      
4. X-ray. Existing hand radiographs will be used in case these are not more than 6 months old. 
5. Selection of target hand. 
 
6.8.8 
Visit 3: Baseline visit 
Participants will be asked to refrain from paracetamol and NSAID 24 hours prior baseline visit. Participants 
will also be asked to avoid any oral steroid, intramuscular steroids or steroids injections in other joints 
within 30 days prior visit 3. At the baseline visit the following procedures will be completed in this order: 
1. DECT 
2. CBCT 
3. Pregnancy screening. Female fertile participants will be screened for pregnancy by testing for urine 
human chorionic gonadotropin. 
4. Patient reported outcomes: See table 5. 
5. Update medical history to adjust for any new events or treatments. 
6. Hand photos 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 39 af 65 
 
7. Objective examination: See table 5. 
8. Ultrasound 
9. Randomization 
10. Scheduling of next visits 
 
6.8.9 
Visit 4: Week 4 telephone visit  
The week 4 visit will be a telephone visit. Participants will be asked to refrain from medication as described 
at the baseline visit 3. Following procedures will be completed in this order: 
1. Patient reported outcomes: See table 5. Scoring will be done by emailing individual internet 
hyperlink questionnaires. Participants will be directed to a secure webpage for online answering 
and the electronic system RedCap will be used for capture of data. If participants do not have 
access to email or online scoring of questionnaires, the questionnaires can be filled out by 
telephone interview.  
2. Pregnancy screening. Female fertile participants will be screened for pregnancy by testing for urine 
human chorionic gonadotropin. Urine screening will be done at home and reported in the RedCap 
questionnaire. If participants fail to fill out test results, this will be requested upon telephone 
interview. 
3. Safety recording: See table 5. Recording will be done by telephone interview.  
4. Assessment of treatment adherence by telephone interview.  
 
6.8.10 Visit 5: Pregnancy home screening 
Female fertile participants will be screened for pregnancy by testing for urine human chorionic 
gonadotropin, urine screening will be done at home and reported to the investigator or his/her delegate 
using telephone or email. If the participant fails to contact the investigator within the timeframe, the 
investigator or his/her delegate will contact the participant. 
 
6.8.11 Visit 6: Week 12 visit 
Participants will be asked to refrain from medication as described at the baseline visit 3. The primary 
endpoint at week 12 will assess the following in this order:  
1. Laboratory test: Blood sample, cf. safety and exploratory outcomes. For fertile female participants, 
this will also include pregnancy screening. A complete list of blood samples throughout the trial is 
available in Appendix 1. Parameters ≤ 1 week old need not be repeated.  
2. Patient reported outcomes: See table 5. 
3. Update medical history to adjust for any new events or treatments. 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 40 af 65 
 
4. Safety recording: See table 5. 
5. Assessment of treatment adherence 
6. Objective examination: See table 5. 
7. Ultrasound 
 
6.8.12 Visit 7: Post-study week 16 
At week 16 a post-study telephone visit take place. The visit is not part of the study. The following will be 
assessed: 
1. Updated medical history with focus on study drug withdrawal symptoms and general hand OA 
symptoms. 
2. Safety recording: See table 5. 
3. Pregnancy screening. Female fertile participants will be screened for pregnancy by testing for urine 
human chorionic gonadotropin. Urine screening will be done at home and reported by telephone 
interview. 
4.  
 
6.8.13 Visit 8: Pregnancy home screening 
Female fertile participants will be screened for pregnancy by testing for urine human chorionic 
gonadotropin, urine screening will be done at home and reported to the investigator or his/her delegate 
using telephone or email. If the participant fails to contact the investigator within the timeframe, the 
investigator or his/her delegate will contact the participant. 
 
6.8.14 Visit 9: Pregnancy home screening 
Identical to visit 8, please see description above.  
 
6.8.15 Delegation of study visits 
Investigator can delegate visit 1-9 to any medical doctor affiliated with the Parker Institutes outpatient OA 
clinic who is familiar with the project and GCP guidelines. Visit 4, 5 and the post-study visits 7-9 can also be 
delegated to a nurse with research expertise affiliated with the Parker Institutes outpatient OA clinic who is 
familiar with the project and GCP guidelines. 
 
6.8.16 Study completion 
The end-of-study is defined as the date of the last participant's last scheduled visit. 
  

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 41 af 65 
 
6.8.17 Protocol violations 
Protocol violations will be registered in the CRF, but participants may continue the study, i.e. participants 
with protocol violations and deviations will still be invited for outcome collection and follow-up.  
Participants with protocol violations occurring after randomization, will not be replaced by new 
participants.  
 
6.8.18 Participant retention and follow-up (drop-outs) 
Participants will schedule study visits over the phone. Visits will be confirmed by emailing appointments via 
the public secure mail system, e-boks. If participants fail to meet the appointment, they will be contacted 
by telephone and rescheduled for a new appointment. If the participant is prevented from attending the 
appointment, telephone consultation will be used to minimize missing data. If a participant fails to attend a 
study visit three times in a row and cannot be reached by telephone when contacted on three separate 
days, they will be sent a letter of notification. The letter will state that unless they contact the department 
within 14 days, they will be terminated from the trial and no further contact attempts will be made. Drop-
outs after randomisation will not be replaced by new participants. 
 
6.9 Allocation 
A computer-generated randomisation sequence will be produced before patients are enrolled, allocating 
participants to treatment with oral colchicine 0.5 mg bid or placebo (1:1). Randomisation will be in permuted 
blocks; block sizes will be unknown to the investigator and his/her delegate. The randomisation will be 
stratified on age (<75, ≥75), BMI (<30, ≥30) and gender (male/female).The randomisation sequence is 
generated by a biostatistician (RC), both the biostatistician and the central pharmacy of the capital region 
stores the randomisation list. Subjects will be assigned individual treatment numbers. Numbers will be listed 
on the study treatment etiquettes, to ensure that subjects are receiving the study drug or placebo according 
to the treatment allocation. Treatment number will be registered in the eCRF once participant has been 
randomised. 
The study utilizes a computer-generated allocation concealment process, which ensures that the group 
to which the patients is allocated is not known before the patient is entered into the study. 
 
6.10 Sample size and power considerations 
We set minimal clinical important difference for change in finger joint pain from baseline to week 12 to 15 
mm (VAS 0 to 100 scale), as used in previous hand OA trials [44, 45]. Based on previous trials [44, 45] we 
assume a standard deviation (SD) of 22 for the change in VAS finger joint pain over time. The standardised 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 42 af 65 
 
Cohens effect size 0.7 (mean difference divided by SD) is equivalent to a medium to large effect when using 
Cohens’ cut-off sizes (0.2: small, 0.5: medium, 0.8 large) [46].   
 
At a power of 90% and 80% and a p-value of 0.05 a sample size will be needed of at least 46 
and 35 per group respectively. To take loss-of-follow up into account we aim to include 100 patients. 
Sample size calculations were performed in R studio (Version 1.2.1335, RStudio Team (2018). RStudio: 
Integrated Development for R. RStudio, Inc., Boston, MA URL, http://www.rstudio.com/).  
 
7 METHODS: Assignment of interventions 
7.1 Blinding 
By providing a placebo identical to the intervention we aim to achieve blinding of participants, care 
providers and outcome assessors. Data analysists will be blinded throughout analysis. The data manager 
will provide a blinded data output for analyses. 
All participants are assigned a participant number and a treatment number upon randomisation. Both are 
unique. Study medication is labelled with the treatment number. The pharmacy provides sealed envelopes 
marked with a treatment number alongside study medication. The sealed envelopes will be stored 
separately from the medicine in a locked room at the Parker Institute.  
 
7.2 Unblinding 
Unblinding can occur immediately and without restrictions if necessary, by contacting the investigator. The 
investigator can look up the participants treatment number in the eCRF. The investigator can then open a 
physical envelope labelled with the treatment number and the envelope will contain information of the 
true content of study medication (colchicine or placebo). Each treatment number has its own envelope and 
unblinding of a participant does not collaterally unblind other participants.    
 
8 METHODS 
8.1 Data collections methods 
Data collection methods are specified in the outcomes section.  
 
8.2 Data management 
Data management will adhere to the standard requirements for Good Clinical Practice (GCP)-compliant 
data management in clinical trials. Sponsor will organize GCP monitoring together with the GCP-unit 
(address on the title page).  

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 43 af 65 
 
 
8.2.1 
Source Documents 
Source documents are defined as original documents, data and records. This may include hospital records, 
clinical and office charts, laboratory data/information, participants' diaries or evaluation checklists, health 
professionals’ records or charts, and other records, recorded data from automated instruments, and X-rays.  
The investigator(s)/institution(s) will permit study-related monitoring, audits and regulatory 
inspection(s), providing direct access to source data documents.  
DECT and CBCT will be made available for further imaging analyses in collaboration with the 
Department of Radiology, Bispebjerg and Frederiksberg Hospital, headed by MB. The imaging-analyses 
team will be blinded to other clinical trial data. The results will be transferred back to the data management 
team for further processing and subsequent analyses. 
 
8.2.2 
Case Report Forms 
The study will use electronic case report forms (eCRF) using an on-line web-based clinical trial management 
application (RedCap) and an in-house custom-built electronic data capture system (Cirkeline).  
RedCap allows individual patients to supply data from home and clinical and data can be entered by staff 
who has been granted permissions.  
Cirkeline allows individual patients to supply questionnaire data at clinical visits via touch-screens in the 
clinic, as well as entering of study related data by the staff. 
At the end of the trial, all data will be merged and stored in the RedCap application. Upon completion of 
data entry, the database will be checked to ensure acceptable accuracy and completeness. System backups 
and record retention for the study data will be consistent with The Parker Institutes standard procedures. 
The applications meet all regulatory standards and allow management of all activities related to clinical 
trials that ensures optimal resource use and safety according to good clinical practice and data protection 
legislation. 
 
8.2.3 
Data management upon completion of data entry 
Upon completion of data entry, the databases will be checked to ensure acceptable accuracy and 
completeness. System backups and record retention for the study data will be consistent with The Parker 
Institute standard procedures. All clinical data will be made available in an anonymised state to the data 
management team, led by the investigator. The team will make available a dataset for the statistical 
analysis. The statistician will be blinded throughout the analyses-phase. 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 44 af 65 
 
 
The source data and documents, protocol and amendments, drug accountability forms, 
correspondence, patient identification list, informed consent forms, and other essential GCP documents will 
be retained for at least 10 years after the study is completed at the study site. Any data captured electronically 
will be stored electronically in a separate database according to standard procedures at The Parker Institute.   
The data collected in the clinical trial will upon request be made available for further exploitation in 
the research community upon publication of the main results of the studies. The Parker Institute guarantees 
to ensure future data storage, protection, and availability. 
 
8.2.4 
Data Protection Act and General Data Protection Regulation 
The study will be conducted in accordance with the Data Protection Act and follow the General Data 
Protection Regulation. The study data management and data security procedures are approved by the 
Regional Knowledge Centre on Data Protection Compliance (Videnscenter for dataanmeldelser i Region 
Hovedstaden) on behalf of the Danish Data Protection agency (file no.: P-2020-138). 
 
8.3 Statistical methods 
Categorical data, e.g. the number of randomised patients will be summarized as total by using counts and 
percentages. Continuous variables will be presented as means with corresponding variation presented as 
SD, for skewed data medians and percentiles will be considered instead.  
 
8.3.1 
Analysis population 
Efficacy and safety analysis will use the intention-to-treat population (ITT) for primary analysis. The ITT 
population will also be used for calculating percentages in categorical data. The ITT population consist of all 
randomised patients irrespective of whether the patient received study intervention or the patient’s 
compliance with the study protocol, in the treatment group to which the participant was assigned at 
randomisation. A patient will be considered randomised as soon as a treatment is assigned by according to 
the allocation sequence. 
Sensitivity analysis will also be done on the as-observed population (AO) and the per 
protocol population (PP). The AO population consists of participants who has the outcome of interest 
assessed at any given time point of interest (i.e. no imputation of missing data will be done). The PP 
population consist of all patient meeting the study criteria, with no protocol violation, who completed the 
study. As drop-out or protocol violation may occur throughout the trial, the AO and PP population can 
differ at varying timepoints. The AO and PP population can be identical if all participant in the AO 
population adhered to protocol.  

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 45 af 65 
 
For analysis concerning inflammation analysis population will only include participants who 
refrained from anti-inflammatory medication (i.e. NSAID and corticosteroids) prior baseline visit 3 and the 
week 12 visit, this population will be referred to as per ultrasound protocol. Thus, they will still be included 
in inflammation analysis if other protocol violations occur.   
  
8.3.2 
 Missing data 
Missing data will not be imputed for descriptive statistics. Missing outcome data will be handled by 
multiple imputation.  
 
8.3.3 
Primary outcome 
Assessments of changes from baseline and construction of CIs for continuous measures will be based on a 
repeated measures analysis of covariance (ANCOVA; including group as the main factor and baseline 
measure as covariate). Outcome will be presented as point estimate of the differences between the two 
treatment arms. Corresponding CI of 95% and two-sided p-value will be presented. A p-value < 0.05 is 
considered significant. A difference in treatment effect between colchicine and placebo can be considered 
truly present, if CIs does not overlap between two treatment arms. Superiority will be claimed if the 
computed 95% confidence interval of the estimated group difference in the change from baseline in the 
VAS pain scale does not include 0 in the ITT population. The primary analysis will be adjusted for baseline 
VAS pain. In case of relevant between-group differences at baseline in other important covariates, the 
primary analysis will be adjusted for those.  Statistical analysis will be done in R studio (Version 1.2.1335, 
RStudio Team (2018). RStudio: Integrated Development for R. RStudio, Inc., Boston, MA URL, 
http://www.rstudio.com/). 
 
8.3.4 
Secondary outcomes 
Secondary outcomes will be analysed analogous to the above model for the continuous outcomes. 
Dichotomous endpoints will be presented as categorical data and compared using a two-sided significance 
test. The OMERACT-OARSI responder criteria incorporate changes from baseline, so there is no need to 
adjust for baseline data.  
 
8.3.5 
Exploratory outcomes 
Exploratory outcomes will be analysed analogous to the above model for the continuous outcomes.  
Stratified subgroup analysis will also adhere to the ITT population as defined. To avoid type I errors due to 
multiple comparisons, efficacy will only assess the primary outcome VAS finger joint pain. Analysis will be 
stratified based on inflammation (yes/no), crystal (yes/no), and type of crystal (MSU/CPP/HA). The latter 
will only be performed on the population who have crystals.  

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 46 af 65 
 
 
8.3.6 
Statistical analysis plan 
The statistical analysis plan will be reviewed again and described in detail before execution of analysis and 
before unblinding the treatment allocation.  
 
9 RESEARCH ETHICS 
Prior to screening, all potential trial participants are informed, both orally and in writing, about the purpose 
of this trial, its process and potential risks, as well as costs and benefits of participation. In addition, the 
leaflet ”Rettigheder som forsøgsperson i et sundhedsvidenskabeligt forskningsprojekt [Rights as a 
participant in a health research project]” will be handed out. All participants are informed of their rights to 
withdraw from the study at any time without this impacting on any future investigations and/or treatments 
at any site or by some of the members of the study group. After the information is delivered, read and 
understood, voluntary informed consent is given by the participant by signing a consent form before trial 
participation can take place. 
 
9.1 Oral information 
Oral information will be provided in agreement with the guideline presented in appendix 5. When a 
potential participant contacts the trial, an appointment for an information interview is made. It will be 
stressed that the investigator is asking the participant to consider participation in the trial, and that the 
potential trial participant has the right to bring a companion to the information interview. The written 
information material will be handed out or sent by e-boks to the potential trial participant so that he or she 
has at least 24 hours to read the material before the information interview. 
The oral information is based on the written information and will be given in a language easily understood 
without technical or value-laden terms. The information will be given in a considerate way that is tailored 
to each potential trial participants. The aim is that the conversation takes place without interference. It is 
the responsibility of the interviewer to ensure that the potential trial participant has understood the 
information. The information interview is performed by the investigator or his/her delegate.  
 
9.2 Written information 
A written information material for the patient is available in appendix 6. 
  

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 47 af 65 
 
9.3 Informed consent 
Consent to participation in the trial is given based on the written and oral information. 
An informed consent form (ICF), appendix 7, has been prepared. The form must be signed and dated by the 
participants prior to participation in the trial. A copy of the form is provided to the participants. The 
investigator or his/her delegates can receive the signed consent form. Prior to consent, it must be ensured 
that a potential participant has been given enough time to consider his or her participation. 
The source documentation and CRFs will document for each participant that informed consent was 
obtained prior to participation in the study. The signed ICF must remain in each participant’s study file and 
must be available for verification by study monitors at any time. 
 
9.4 Risk associated with the intervention 
There are well known AEs related to oral colchicine treatment, mainly from the gastrointestinal system 
(loose bowel movements, abdominal pain, dyspepsia). All studies have reported occurrence of these events 
but have found them to be mild and without significant difference between tablet colchicine and 
comparator arm [23-26]. No serious AEs have been reported in recent clinical trials [23-26]. Oral colchicine 
0.5 mg bid is therefore considered safe and well-tolerated. The participants are followed closely and will 
have the ability to contact the study investigator or delegates, if they need help managing AE or if 
unforeseen AE should occur.  
In case of AE participants will be evaluated by a medical doctor and assessed individually. Dose 
modification may be necessary.  
According to the Danish Medicines Agency Product Resumé for tablet colchicine (appendix 4) animal 
studies have shown reproductive toxicities related to colchicine. In humans, rare cases of reversible 
oligospermia or azoospermia have been described among men. Among pregnant women current data 
indicate that malformations and foetal or neonatal toxicities does not occur due to treatment with 
colchicine. In case of pregnancy within the treatment period or respectively 3 and 6 months after end of 
treatment for female and male participants, the couple will be referred to genetic counselling.    
The intervention is considered justifiable in a health research ethics perspective. Known AEs are 
summarized in table 6. 
 
9.4.1.1 
Table 6: Colchicine AEs   
Frequency Side-effect 
1-10% 
Abdominal pain. Diarrhea. Nausea. Vomiting 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 48 af 65 
 
Unknown 
Gastrointestinal hemorrhage. Hepatotoxicity. Bone marrow depression. Myopathy. 
Rhabdomyolysis. Neuropathy. Peripheral neuritis. Alopecia. Amenorrhea. Reduced kidney 
function. Oligospermia.    
Colchicine AE. Table reproduced from pro.medicin.dk without editing [47]. 
 
9.4.2 
Colchicine safety in drug-drug interactions 
Treatment with drugs known to inhibit cytochrome P450 3A4  and P-glycoprotein can increase the plasma 
concentration of colchicine [48], increasing the risk for colchicine related adverse effects. The United States 
Food and Drug Administration (FDA) recommends that P-glycoprotein inhibitors and strong CYP3A4 
inhibitors are not co-administered with oral colchicine in people with impaired kidney or liver function. In 
case of normal kidney and liver function, concomitant treatment are accepted, but dose reduction of oral 
colchicine is recommended [49]. Grapefruit is a moderate CYP3A4 inhibitor. The FDA advise for dose-
reduction when consuming grapefruit, while Danish recommendation consider it safe [50]. The 
pharmacokinetics of oral colchicine was not altered when 240 mL of grapefruit juice was consumed twice a 
day [51], and consumption within this range will be accepted in the current study. The potential interaction 
between statins and oral colchicine is not clear. Danish recommendations advise caution, allowing 
concomitant treatment but advise focus on symptoms related to acute myopathy [50]. Previous studies of 
oral colchicine 0.5 mg bid for knee OA did not exclude participants receiving statins and none of these trials 
have reported cases of acute myopathy nor a significant increase in symptoms related to myopathy such as 
myalgia or musculoskeletal pain [23-26]. In a trial assessing the efficacy and safety of continuous treatment 
with oral colchicine 0.5 mg once daily after myocardial infarction, 98.9% of the 2339 participants treated 
with oral colchicine where taking statins. The trial had no separate report on AE such as myopathy or 
myopathy related symptoms, but noteworthy there was no difference in occurrence of any AE or any SAE 
between intervention and placebo group [52]. We will adhere to national recommendations and allow 
concomitant treatment with statins, along with careful participant information. All participants will be 
provided with a study-participant card, to be always carried, which will contain information of the current 
study and study medication. The study-participant card contains contact information of a study investigator 
that can be contacted, see appendix 8.    
The study specific action for people taking treatment that inhibits P-glycoprotein or CYP3A4 are 
summarized in table 7.      
 
9.4.2.1 
 Table 7: Colchicine drug-drug interaction 
Classification 
Drugs 
Recommendation 
Study specific  

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 49 af 65 
 
P-glycoprotein 
inhibitors 
Cyclosporine* 
Ranolazine 
Tacrolimus* 
Colchicine dose-reduction 
[48]. 
 
Potential interaction [50]. 
Excluded or treatment 
terminated 5 half-lifes 
before initiation of study 
drug.  
Strong CYP3A4 
inhibitors 
Atazanavir 
Clarithromycin1 
Darunavir (with ritonavir) 
Indinavir 
Itraconazole 
Ketoconazole1 
Lopinavir (with ritonavir) 
Nefazodone 
Nelfinavir 
Ritonavir1 
Saquinavir 
Telithromycin 
Tipranavir (with ritonavir) 
Colchicine dose-reduction 
[48]. 
 
Potential interaction, 
recommend control of 
creatine kinase [50]. 
Excluded or treatment 
terminated 5 half-lifes 
before initiation of study 
drug.  
 
Moderate 
CYP3A4 
inhibitors 
Amprenavir 
Aprepitant 
Diltiazem1 
Erythromycin 
Fluconazol 
Fosamprenavir 
Verapemil1 
Grapefruit juice 
 
Colchicine dose-reduction 
[48]. 
Colchicine and verapamil co-
treatment should be avoided 
[50]. 
Colchicine and grapefruit 
juice is safe, no dose 
reduction required [50]. 
Excluded or treatment 
terminated 5 half-lifes 
before initiation of study 
drug. 
Grapefruit and grapefruit 
juice allowed but may not 
exceed 240 mL of 
grapefruit juice twice a 
day or equivalent.  
Weak CYP3A4 
inhibitors 
Azithromycin1 
No dose-reduction required 
of  colchicine 
[48]. 
Caution for musculoskeletal 
side-effects [50]. 
Not excluded. 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 50 af 65 
 
Uncategorized 
CYP3A4 
inhibitors 
Disulfiram 
Gemfibrozil 
Telapravir 
 
Potential interaction with 
colchicine when kidney or 
liver function are impaired  
[50]. 
Not excluded. 
Lipid-lowering 
CYP3A4 
inhibitors 
Simvastin 
Atorvastatin 
Pravastatin 
Potential interaction with 
colchicine, focus on 
symptoms related to acute 
myopathy [50]. 
Not excluded. Careful 
participant information.  
The table is modified from Terkeltaub et al., 1refers to the drugs studied in the trial [48]. Third column 
summarizes recommendations from the Danish database of interactions, controlled and hosted by the 
Danish Medicines Agency [50] and from the Terkeltaub study [48] on which the U.S. Food and Drug 
Administration bases their recommendations. Fourth column summarizes the study specific action for 
people taking treatment presented in column two. 
 
9.5 Risk associated with study participation 
9.5.1 
Questionnaires and physical examination 
The methods are non-invasive and is not associated with any predictable risks. The procedures are 
considered justified in a health research ethics perspective. 
 
9.5.2 
Blood samples 
Blood sampling can be associated with a short painful experience when the skin is penetrated by the 
sampling needle, and afterwards the participant may have a small subcutaneous haemorrhage and 
discoloration. This information will be included in the oral and written information. 
The knowledge gained by this examination is commensurate with the efforts and difficulties associated 
with participation. The procedure is considered justifiable in a health research ethics perspective. 
 
9.5.3 
Radiation safety 
The effective dose for a single X-ray image of a hand is approximately 3 μSv, in this study both hands will be 
X-rayed, so total effective X-ray radiation dose for participation in this trial will be 6 μSv. The total effective 
dose for DECT hand scans is 16 μSv. The effective X-ray dose for one scan of the hand with the CBCT 
(Carestream Onsight 3D Extremity System) equipment used is maximum of 40 μSv (5-40 μSv). The annual 
background radiation in Denmark is approximately 3000 μSv (≈ 8 μSv / day). When exposed to a dose of 1 
Sv (1,000000 μSv), the risk of causing a cancerous disease increases by 5% over the average risk in the 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 51 af 65 
 
population. The risk increments following exposure in this study is 6 µSv (X-ray both hands) + 16 μSv (DECT 
one hand) + 40 µSv (CBCT one hand) = 62 μSv can be calculated as 0.000062 Sv x 5% per Sv = 0.0000031% 
that should be added to the lifetime risk of dying from cancer of 25% in Denmark, that theoretically will 
change to 25.0000031%. 
 
9.6 Benefit of study participation 
Participants in this trial will receive special consultancies with a medical doctor with a special interest and 
knowledge of hand OA. Examinations in this trial exceeds standard hand OA examination and can give the 
participant a greater insight into their hand OA illness. Participants will not be financially compensated for 
participation.   
 
9.7 Insurance 
The participants are insured by the Danish Patient Insurance Association. Financing and insurance issues 
are addressed in the written information material. 
 
9.8 Health Research Ethical approval 
This protocol, the informed consent form, written patient information, any anticipated advertising 
materials, and relevant supporting information will be submitted to the Health Research Ethics Committee 
system, by the Sponsor, prior to study initiation. The study will be conducted in accordance with Danish 
law, the Helsinki declaration, and Health Research Ethics Committee requirements. 
The Sponsor is responsible for keeping the committee informed of amendments or changes to the protocol, 
and the progress of the study, as appropriate. 
 
10 PERSPECTIVE  
If this study finds a positive effect of tablet colchicine on hand OA symptoms, it could lead the way for a 
new treatment option in patients with hand OA. This will benefit both the individual patient and society, as 
hand OA is a costly disease with the ability to invalidate patients. A negative finding will also be important. 
In clinical practice treating hand OA can be challenging, and when treatment options have been exhausted 
or are insufficient, clinicians and patients are often tempted to try off-label medication, which may include 
colchicine. A negative finding will hopefully limit off-label colchicine use and spare patients’ unnecessary 
side-effects and medical expenses. In case of inconclusive results, this study may point the way for future 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 52 af 65 
 
research as it includes a broad hand OA population, and will explore if subgroups differ in tablet colchicine 
treatment effects.      
 
11 PATIENT INVOLVEMENT 
Two patient research partners (PRPs), Ulla Dal and Kirsten Baldo, with hand OA were involved in the 
designing process of this study, which follows the EULAR recommendations [53]. The PRP work is voluntary. 
The PRPs were identified at the Parker Institutes outpatient clinic and invited to participate. Prior to their 
decision of participation, they received a written and oral task description that clarified their roles and 
expected contributions. They were invited to comment on the entire protocol and study design, and 
requested to focus on study relevance, outcomes and treatment duration. Both PRPs approved the design, 
intervention (dose and duration), outcomes and the remainder of the protocol, including appendixes. They 
supported pain as the primary objective and requested the secondary objective to be function. This request 
was met. Both PRPs were concerned about AE and underlined the importance of possible contact with the 
investigator (or his/her delegate) in case of AE. Both PRPs supported the current design with respect to 
safety.  
The HAQ-DI questionnaire was criticised for not offering response option equal to “med lidt besvær 
[with little trouble]” but moves from “uden besvær [no trouble]” to “med noget besvær [with some 
trouble]”. The BIPQ was criticised for not including a self-centred reflection question on prevention “Tror 
du selv du kan gøre noget for at forebygge din sygdom? [Do you think you can do anything to prevent your 
disease?]”. Questionnaires were not altered but kept in original validated translations. 
The PRPs will prospectively be invited to participate in discussion of results and contribute to the core 
publication. The PRP may contact the research group whenever needed. The PRP can be offered co-
authorship in relation to publication according to the recommendations from the International Committee 
of Medical Journal Editors (ICMJE) criteria. 
 
12 PUBLICATION 
Development of the core publication will be coordinated by the executive committee, whose membership 
includes the investigator and delegates who provided significant input into study design, implementation, 
conduct and interpretation. Authors include the members of the executive committee and possibly other 
key study personnel (to be agreed upon by the executive committee) who has contributed significantly to 
the implementation and conduct of the study and non-site personnel who contribute substantially to the 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 53 af 65 
 
design, interpretation or analysis of the study and fulfil the requirements for authorship as recommended 
by the ICMJE.  
Development of secondary and/or substudy publication(s) will be coordinated by the 
executive committee. A named author approach will be utilized (authors to be agreed upon by executive 
committee) under the criteria recommended by ICMJE as above. 
In accordance with the principles of the Helsinki declaration, all results of the study, positive 
as well as negative and inconclusive will be published. 
Activities that alone (without other contributions) do not qualify a contributor for authorship include 
but are not limited to: acquisition of funding; general supervision of a research group or general 
administrative support; and writing assistance, technical editing, language editing, and proofreading. Those 
whose contributions do not justify authorship may be acknowledged individually or together as a group 
under a single heading (e.g. "Clinical Investigators" or "Participating Investigators"), and their contributions 
will be specified (e.g., "served as scientific advisors," "critically reviewed the study proposal," "collected 
data," "provided and cared for study patients", "participated in writing or technical editing of the 
manuscript"). Written permission to be acknowledged from all acknowledged individuals will be collected 
prior to submission of a manuscript for publication. 
 
13 FUNDING 
The study is initiated by Professor Henning Bliddal and Ph.D. student Anna Døssing who has received 
funding from the IMK foundation (DKK 920.000 Ph.D. student salary), the A.P. Møller foundation (DKK 
55.000 statistical assistance and database consultant), the Aase and Ejnar Danielsens Foundation (DKK 
100.000 microscopy, publication fees, radiograph assistance, statistical assistance and database 
consultant), and the Danish Medical Association (DKK 100.000 radiograph assistance, statistical assistance 
and database consultant). The Parker Institute is also supported by a core grant from the Oak Foundation 
(OCAY-18-774-OFIL). All funding is paid to the Parker Institute which administers the economy. None of the 
investigators have conflicts of interests related to the funding of this study. This information is disclosed to 
all participants in the written information material. 
 
All sources of support (including technical and financial support) provided for this study is disclosed in the 
written information material and will be disclosed in publication of the study results. Funding is an ongoing 
process. All future financial and/or technical support to the study will be disclosed to all participants 
(previous, current and potential) in the written information material. 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 54 af 65 
 
 
14 CONFLICT OF INTEREST 
Anna Døssing: No conflict of interest. 
Christoph Felix Müller: Employee of Siemens Healthineers. 
Geraldine McCarthy: No conflict of interest. 
Philip Conaghan: No conflict of interest. 
Roy D. Altman: No conflict of interest. 
Lisa Stamp: No conflict of interest. 
Lene Terslev: Speakers fee from Novartis, Lilly, BMS, AbbVie, Roche and GE 
Margreet Kloppenburg: No conflict of interest. 
Ida Haugen: Research grant from Pfizer 
Elisabeth Marie Ginnerup-Nielsen: No conflict of interest. 
Mikael Boesen: No conflict of interest. 
Robin Christensen: No conflict of interest. 
Henning Bliddal: No conflict of interest. 
Marius Henriksen: No conflict of interest. 
Fabio Becce: Has received personal consulting fees from Horizon Therapeutics, unrelated to this work. 
 
15 ROLES AND RESPONSIBILITY 
All authors participated in study design. AD drafted the protocol. All authors critically reviewed and 
approved the protocol. 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
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16 APPENDIXES 
16.1 Appendix 1: Laboratory samples 
Parameters ≤ 1 week old need not be repeated, except anti-cyclic citrullinated peptide, were measures ≤ 1 
year old need not be repeated. Only female fertile participants will be pregnancy screened (human 
chorionic gonadotropin). Only female postmenopausal participants will have postmenopausal state 
confirmed by measurement of follicle stimulating hormone.      
Blood sample 
Unit 
Purpose 
Sample collected 
Screening Outcome Safety Visit 2 
Visit 6 
Urate 
mM 
 
X 
 
X 
X 
Ionized calcium 
mM 
 
X 
 
X 
X 
Magnesium 
mM 
 
X 
 
X 
X 
C-reactive protein 
mM 
 
X 
 
X 
X 
White-cell (leucocytes) differential count *109/L 
X 
 
X 
X 
X 
Haemoglobin 
mM 
X 
 
X 
X 
X 
Hematocrit  
% 
X 
 
 
X 
 
Erythrocyte mean corpuscular volume 
mM 
X 
 
 
X 
 
Platelet count (thrombocytes) 
*109/L 
X 
 
X 
X 
X 
Creatine kinase 
U/L 
X 
 
X 
X 
X 
Alanine transaminase 
U/L 
X 
 
X 
X 
X 
Creatine clearance 
mL/min 
X 
 
X 
X 
X 
Sodium 
mM 
X 
 
X 
X 
X 
Potassium 
mM 
X 
 
X 
X 
X 
Anti-cyclic citrullinated peptide  
kU/L 
X 
 
 
X 
 
Human chorionic gonadotropin 
IU/L 
X 
 
X 
X 
X 
Follicle stimulating hormone 
IU/L 
X 
 
 
 
 
 
 
 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 56 af 65 
 
16.2 Appendix 2: Paracetamol and NSAID diary 
MEDICINDAGBOG 
Under hele forsøget bedes du dagligt angive brug af smertestillende medicin (præparat, dosis og antal) 
Navn: _________________________________________________________________  Id: _______________________ 
Dato 
Har ikke 
taget 
nogen 
Panodil 
Pamol 
Pinex 
Ipren 
Ibuprofen 
Ibumetin 
Andet 
Årsag 
Dosis 
(mg) 
antal 
Dosis 
(mg) 
antal 
Dosis 
(mg) 
antal 
Dosis 
(mg) 
antal 
Dosis 
(mg) 
antal Dosis 
(mg) 
antal 
Dosis 
(mg) 
antal 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 57 af 65 
 
MEDICINDAGBOG 
Under hele forsøget bedes du dagligt angive brug af smertestillende medicin (præparat, dosis og antal) 
Navn: _________________________________________________________________  Id: ________________________ 
Dato 
Har ikke 
taget 
nogen 
Panodil 
Pamol 
Pinex 
Ipren 
Ibuprofen 
Ibumetin 
Andet 
Årsag 
Dosis 
(mg) 
antal 
Dosis 
(mg) 
antal 
Dosis 
(mg) 
antal 
Dosis 
(mg) 
antal 
Dosis 
(mg) 
antal Dosis 
(mg) 
antal 
Dosis 
(mg) 
antal 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 58 af 65 
 
MEDICINDAGBOG 
Under hele forsøget bedes du dagligt angive brug af smertestillende medicin (præparat, dosis og antal) 
Navn: _________________________________________________________________  Id: ________________________ 
Dato 
Har ikke 
taget 
nogen 
Panodil 
Pamol 
Pinex 
Ipren 
Ibuprofen 
Ibumetin 
Andet 
Årsag 
Dosis 
(mg) 
antal 
Dosis 
(mg) 
antal 
Dosis 
(mg) 
antal 
Dosis 
(mg) 
antal 
Dosis 
(mg) 
antal Dosis 
(mg) 
antal 
Dosis 
(mg) 
antal 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 59 af 65 
 
MEDICINDAGBOG 
Under hele forsøget bedes du dagligt angive brug af smertestillende medicin (præparat, dosis og antal) 
Navn: _________________________________________________________________  Id: ________________________ 
Dato 
Har ikke 
taget 
nogen 
Panodil 
Pamol 
Pinex 
Ipren 
Ibuprofen 
Ibumetin 
Andet 
Årsag 
Dosis 
(mg) 
antal 
Dosis 
(mg) 
antal 
Dosis 
(mg) 
antal 
Dosis 
(mg) 
antal 
Dosis 
(mg) 
antal Dosis 
(mg) 
antal 
Dosis 
(mg) 
antal 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 60 af 65 
 
MEDICINDAGBOG 
Under hele forsøget bedes du dagligt angive brug af smertestillende medicin (præparat, dosis og antal) 
Navn: _________________________________________________________________  Id: ________________________ 
Dato 
Har ikke 
taget 
nogen 
Panodil 
Pamol 
Pinex 
Ipren 
Ibuprofen 
Ibumetin 
Andet 
Årsag 
Dosis 
(mg) 
antal 
Dosis 
(mg) 
antal 
Dosis 
(mg) 
antal 
Dosis 
(mg) 
antal 
Dosis 
(mg) 
antal Dosis 
(mg) 
antal 
Dosis 
(mg) 
antal 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
Side 61 af 65 
 
16.3 Appendix 3: Efficacy outcomes 
Questionnaires and scoring sheets for efficacy outcomes are available as a separate document. 
 
16.4  Appendix 4: Danish Medicines Agency Product Resumé for tablet colchicine 
“Tiofarma” 
The product resume is available in Danish as a separate document. Product resume was updated 
13.03.2020. 
  
16.5 Appendix 5: Guideline for oral information 
Guideline for oral information is available in Danish as a separate document.  
 
16.6 Appendix 6: Written information 
Written information for potential trial participants in Danish is available as a separate document.  
 
16.7 Appendix 7: Informed consent form 
An informed consent form in Danish is available as a separate document. 
 
16.8 Appendix 8: Study participant card 
A study participant card is available in Danish as a separate document. 
 
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PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
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PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
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PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
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PROTOCOL: Colchicine treatment for patients with hand osteoarthritis: A randomized, placebo-controlled trial. 
AUTHOR: The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital 
DATE: 24.11.2020. VERSION: 3. EudraCT: 2020-002803-20  
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