Condition category
Digestive System
Date applied
01/09/2020
Date assigned
05/09/2020
Last edited
03/09/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Chronic pancreatitis is a condition where the pancreas has become permanently damaged from inflammation and stops working properly. The pancreas is a small organ, located behind the stomach, that helps with digestion. Chronic pancreatitis can affect people of any age, but it usually develops between the ages of 30 and 40 as a result of heavy drinking over many years. It's more common in men.
Chronic pancreatitis is associated with a markedly reduced life expectancy and quality of life. In a recently performed study, current care for patients with chronic pancreatitis in the Netherlands proved not to be in accordance with the in 2017 published European guideline.
The aim of the present study is to assess whether standardized care through the implementation of an evidence-based management 'algorithm' of interventions for patients with chronic pancreatitis results in an improvement in quality of life and reduction of pain severity as compared to current practice.

Who can participate?
Chronic pancreatitis patients who meet the in- and exclusion criteria and are receiving active treatment in one of the participating centers of the Dutch Pancreatitis Study Group.

What does the study involve?
All participating hospitals cross over from current practice, to care according to the treatment algorithm. The sequence of crossing over is randomized. Study participants will be enrolled during the current practice phase and be followed until the end of the study. In the end, this evidence-based management algorithm will be implemented in all participating hospitals. The evidence-based management algorithm consists of a combination of interventions, based on the recommendation of the United European Gastroenterology evidence-based guidelines will be compared with care according to current practice.

What are the possible benefits and risks of participating?
There are no additional/potential risks for participating in this trial. Possible benefits: During the intervention phase all participating patients will be treated according to our standardized evidence-based management algorithm.

Where is the study run from?
Dutch Pancreatitis Study Group, St. Antonius Hospital (The Netherlands)

When is the study starting and how long is it expected to run for?
July 2020 to July 2023

Who is funding the study?
Mylan (The Netherlands)

Who is the main contact?
Prof. dr. M. Bruno, m.bruno@erasmusmc.nl
Dr. F.E.M. de Rijk , f.de.rijk@antoniusziekenhuis.nl

Trial website

https://combo-studie.nl/

Contact information

Type

Scientific

Primary contact

Miss Florence de Rijk

ORCID ID

Contact details

Koekoekslaan 1
Nieuwegein
3435 CM
Netherlands
+31 (0)88 3207050
f.de.rijk@antoniusziekenhuis.nl

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

NL8556

Study information

Scientific title

Implementation study of an evidence-based management algorithm for patients with chronic pancreatitis: a nationwide stepped-wedge cluster randomized controlled trial (COMBO trial)

Acronym

COMBO

Study hypothesis

The aim of this study is to investigate whether the implementation of an evidence-based management algorithm consisting of a combination of interventions for the management of chronic pancreatitis (CP) results in an improvement of patient outcomes.

Ethics approval

On 21/04/2020 the MEC-U (Medical Research Ethics Committees United; Postbus 2500, 3430 EM Nieuwegein, Koekoekslaan 1, Netherlands; +31 (0)88 3208784; info@mec-u.nl) ruled that this study is not subject to the Medical Research Involving Human Subjects Act (WMO), ref: W20.074

Study design

Nationwide stepped-wedge cluster randomized controlled trial

Primary study design

Interventional

Secondary study design

Stepped-wedge cluster randomized controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

https://combo-studie.nl/ (in Dutch)

Condition

Chronic pancreatitis

Intervention

All participating hospitals cross over from current practice to care according to the treatment algorithm. The sequence of crossing over is randomized. Study participants will be enrolled during the current practice phase and be followed longitudinally until the end of the study. In the end, this evidence-based management algorithm will be implemented in all participating hospitals.

The evidence-based management algorithm consists of a combination of interventions, all considered as part of best practice, based on the recommendations of the United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis (2017) and extensive systematic literature analysis. The interventions included in this algorithm are particularly focused on education of both physicians and patients, management of risk factors for disease progression and regular screening for and treatment of complications of chronic pancreatitis. The final algorithm has been critically reviewed by the advisory committee of international experts in the field of chronic pancreatitis before implementation in this trial.

Follow up will be 18 months after the start of the intervention.

Intervention type

Other

Phase

Drug names

Primary outcome measure

1. Quality of life measured using PANQOLI-questionnaire and EQ5D questionnaire at baseline, start of intervention and 1 year after start of intervention
2. Pain measured using Izbicki questionnaire at baseline, start of intervention and 12 months after start of intervention

Secondary outcome measures

1. Individual clinical outcomes measured using data from medical records combined with data from questionnaires at start of intervention and 12 months after start of intervention
2. Risk factors for disease progression measured using data from medical records combined with data from questionnaires at start of intervention and 12 months after start of intervention
3. Healthcare resource utilization measured using data from medical records combined with data from questionnaires at start of intervention and 12 months after start of intervention
4. Social participation measured using data from medical records combined with data from questionnaires at start of intervention and 12 months after start of intervention
5. Annual costs measured using data from medical records combined with data from questionnaires at start of intervention and 12 months after start of intervention

Overall trial start date

02/07/2020

Overall trial end date

31/07/2023

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Age ≥18 years
2. A diagnosis of CP according to the M-ANNHEIM criteria
3. Active treatment in one of the participating hospitals
4. Provided written informed consent (IC)

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

120 CP patients with a time since diagnosis ≤3 years

Participant exclusion criteria

1. Women who are pregnant
2. End-stage diseases (<6 months estimated survival) due to cancer, chronic obstructive pulmonary disease and/or congestive heart failure
3. Suspected or established pancreatic malignancies
4. Uncompensated cirrhosis
5. Renal failure (GFR <25 ml/min or who are on dialysis)

Recruitment start date

07/09/2020

Recruitment end date

31/12/2021

Locations

Countries of recruitment

Netherlands

Trial participating centre

Amsterdam UMC, locatie AMC
Meibergdreef 9
Amsterdam
1105 AZ
Netherlands

Trial participating centre

Amsterdam AMC, locatie VUMC
De Boelelaan 1117, 1118
Amsterdam
1081 HV
Netherlands

Trial participating centre

Amphia Ziekenhuis
Langendijk 75
Breda
4819 EV
Netherlands

Trial participating centre

St. Antonius Ziekenhuis
3435 CM
Netherlands

Trial participating centre

Bravis Ziekenhuis
4708 AE
Netherlands

Trial participating centre

Catharina Ziekenhuis
5623 EJ
Netherlands

Trial participating centre

Canisius Wilhelmina Ziekenhuis
6532 SZ
Netherlands

Trial participating centre

Erasmus MC
3015 GD
Netherlands

Trial participating centre

Sint Franciscus Gasthuis
3045 PM
Netherlands

Trial participating centre

Haga Ziekenhuis
2545 AA
Netherlands

Trial participating centre

Isala Ziekenhuis
8025 AB
Netherlands

Trial participating centre

Jeroen Bosch Ziekenhuis
5223 GZ
Netherlands

Trial participating centre

Leids Universitair Medisch Centrum
2333 ZA
Netherlands

Trial participating centre

Maasstad Ziekenhuis
3079 DZ
Netherlands

Trial participating centre

Martini Ziekenhuis
9728 NT
Netherlands

Trial participating centre

Meander MC
3813 TZ
Netherlands

Trial participating centre

Maxima MC
5631 BM
Netherlands

Trial participating centre

Medisch Spectrum Twente
7512 KZ
Netherlands

Trial participating centre

Noordwest Ziekenhuisgroep
1815 JD
Netherlands

Trial participating centre

OLVG
1091 AC
Netherlands

Trial participating centre

Radboud UMC
6525 GA
Netherlands

Trial participating centre

Reinier de Graaf Gasthuis
2625 AD
Netherlands

Trial participating centre

Spaarne Gasthuis
2134 TM
Netherlands

Trial participating centre

UMC Utrecht
3584 CX
Netherlands

Trial participating centre

Ziekenhuis Gelderse Vallei
6716 RP
Netherlands

Trial participating centre

Zuyderland MC
6162 BG
Netherlands

Sponsor information

Organisation

Pancreatitis Werkgroep Nederland

Sponsor details

St. Antonius Ziekenhuis
Koekoekslaan 1
Nieuwegein
3435 CM
Netherlands
+31 (0)88 320 30000
info@pancreatitis.nl

Sponsor type

Research organisation

Website

https://www.pancreatitis.nl/

Organisation

Erasmus University Medical Center

Sponsor details

Department of Gastroenterology
Doctor Molewaterplein 40
Rotterdam
3015 GD
Netherlands
+31 (0)10 7040704
f.derijk@erasmusmc.nl

Sponsor type

Research organisation

Website

http://www.erasmusmc.nl/

Funders

Funder type

Industry

Funder name

Mylan Healthcare B.V.

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer-reviewed journal. The researchers would like to publish their study protocol in the future, so for now this protocol is not available online for non-participating centers.

IPD sharing statement
The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication.

Intention to publish date

31/07/2024

Participant level data

Other

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

03/09/2020: Trial’s existence confirmed by Medical Research Ethics Committees United.