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Prediction Medical Device for Rheumatoid Arthritis (PREDIRA) (PREDIRA)

Primary Purpose

Arthritis, Rheumatoid

Status

Unknown status

Phase

Not Applicable

Locations

Spain

Study Type

Interventional

Intervention

SinnoTest®

Biotherapy prescription without SinnoTest® software

About this trial

This is an interventional treatment trial for Arthritis, Rheumatoid focused on measuring Biological therapy, Predictive software, Quality of life

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients over 18 years old and under 70 years old,
Patients with RA, defined according to the ACR / EULAR 2010 or ACR 1987 criteria,
Patients failing a first anti-TNF, defined as:
Ineffectiveness (which is defined as a DAS28-ESR ≥3.2 and an inadequate response to iTNF according to the usual rheumatologist, which generally includes one or more of the following conditions: persistent swollen and tender joints, persistence of disease activity according to the overall evaluation of the patient, high levels of acute phase reactants and/or dependence of analgesics, nonsteroidal anti-inflammatory drugs or corticosteroids); or
Toxicity(defined as the appearance of any adverse event that the patient's rheumatologist relates to the medication and requires discontinuation),
Effective contraception for patients of childbearing potential (oral contraceptive, intrauterine device, implant, spermicide, surgical sterilization or abstinence),
Patients able to read and understand the modalities of the protocol,
Patients who have dated and signed the informed consent form of the trial,
Stability of treatments (no change) between the selection visit and the inclusion visit (M0).

Exclusion Criteria:

Patients with a contraindication to any bDMARD or methotrexate,
Patients included in another therapeutic evaluation study during this trial,
Surgical intervention programmed during the trial,
Patients with difficulties in understanding the Spanish language,
Patients cannot be followed up 6 months,
Psychosocial instability incompatible with regular monitoring (homelessness, addictive behaviour, antecedent of psychiatric pathology or any other comorbidity that would make it impossible for free and informed consent or limit adherence to the protocol),
Breastfeeding and/or pregnancy. Although there are bDMARD that can be used in pregnancy, since SinnoTest can recommend one that discourages this condition, it is decided to exclude the inclusion of pregnant women.

Sites / Locations

Hospital Universitario La Princesa
Hospital Universitario Ramon y CajalRecruiting
Hospital Universitario Clinico San CarlosRecruiting
Hospital Universitario 12 de OctubreRecruiting
Hospital Universitario de La PazRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

SinnoTest® software

Current practice

Arm Description

SinnoTest® is a therapeutic guidance device for patients suffering from rheumatoid arthritis. Prescription of an original or biosimilar biotherapy (rituximab, adalimumab, abatacept) is possible.

Prescription of biotherapy without the SinnoTest® software which corresponds to current practice (all biotherapies).

Outcomes

Primary Outcome Measures

Incremental Cost Utility ratio at 6 months

This outcome will be calculated as the average differential cost per patient between both study arms (mean costs of the Sinnotest® Arm - mean costs of the Control Arm) divided by the diference in effectiveness between both study arms measured in the number of years of life weighted by the quality of life (QALY: quality-adjusted life year) generated by each of the strategies (mean QALY of the Sinnotest® Arm - mean QALY of the Control Arm). QALY will be measured using the EuroQol-5D. Cost will be considered from a Societal perspective, including both direct and indirect costs The ratio will be expressed in cost (2019 Euros) per QALY earned, which represents the additional cost that will have to be spent to earn a healthy year of life

Secondary Outcome Measures

Budget impact analysis at 6 and 12 months

A budget impact analysis will be carried out if the innovation is deemed efficient. This budget impact analysis will describe the resources consumed and the expenses generated by each scenario, a scenario with the use of SinnoTest® and a scenario without SinnoTest®.

Software's predictive model performance

Sensitivity, Especificity, positve and negative preddicted values of the predictive models using the biomarkers will be assessed on the new clinical data from the 6-month trial.

Description of the variation of the proteomic profile between M0 (biotherapy start date) and M6 (6 months visit)

Based on shotgun and semiquantitative proteomics, the diferences between the proteomic profile at baseline and at M6 will be analyzed

Full Information

NCT ID

NCT04147026

First Posted

October 25, 2019

Last Updated

January 7, 2020

Sponsor

Hospital San Carlos, Madrid

1. Study Identification

Unique Protocol Identification Number

NCT04147026

Brief Title

Prediction Medical Device for Rheumatoid Arthritis (PREDIRA)

Acronym

PREDIRA

Official Title

PRediction mEdical DevIce for Rheumatoid Arthritis: Scale-up of Unique Predictive Online Platform Highly Improving the Quality of Life of Rheumatoid Arthritis' Patient by Personalised and Efficient Biotherapies Prescription

Study Type

Interventional

2. Study Status

Record Verification Date

January 2020

Overall Recruitment Status

Unknown status

Study Start Date

December 16, 2019 (Actual)

Primary Completion Date

July 1, 2020 (Anticipated)

Study Completion Date

January 1, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Hospital San Carlos, Madrid

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

Rheumatoid arthritis (RA) is one of the leading chronic inflammatory rheumatism, with a prevalence of about 0.4% of the population. First-line therapy with synthetic disease modifying anti-rheumatic drugs (including methotrexate) is insufficiently effective in 40% of cases. These patients are then treated with biotherapies. The use of these bio-drugs increases each year, becoming a public health issue and a considerable economic burden. Besides, their growth is just beginning, as they are among the major purveyors of pharmacy innovations. There are about ten bio-drugs currently on the market for rheumatoid arthritis with an average annual treatment cost of 8 to 12 K € per patient. This cost is 20 times higher than that of synthetic disease modifying anti-rheumatic drugs. However, among patients treated with biotherapies, clinical practice shows that about one-third will not respond to the selected drug. In the case of non-response, practitioners currently have no choice but to perform an empirical rotation between the different treatments, because no tool capable of predicting the response or non-response to these molecules is currently available. The study is a prospective, phase III, controlled, multicenter, and randomized, single-blind (patient) clinical trial. Intervention arm: Prescription of biotherapy (rituximab, adalimumab, abatacept) using SinnoTest® software Control arm: Prescription of biotherapy without the SinnoTest® software which corresponds to current practice (all biotherapies). In addition, a sub study will be carried out within this trial to analyse the proteomic profile of the patients included and their modification throughout the study. To study the clinical and pharmacoeconomic impact after 6 months of the use of the SinnoTest® predictive tool in patients with rheumatoid arthritis who have failed to a first anti-TNF biologic agent compared to usual care.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Arthritis, Rheumatoid

Keywords

Biological therapy, Predictive software, Quality of life

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

The study is a prospective, phase III, controlled, multicenter, and randomized in 2 parallel groups, single-blind (patient) with binded outcome assessment clinical trial. Intervention arm: Prescription of biotherapy (rituximab, adalimumab, abatacept) using SinnoTest® software Control arm: Prescription of biotherapy without the SinnoTest® software which corresponds to current practice (all biotherapies).

Masking

ParticipantOutcomes Assessor

Masking Description

The patient will not know if his bDMARD treatment was prescribed with or without the help of SinnoTest® software

Allocation

Randomized

Enrollment

180 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

SinnoTest® software

Arm Type

Experimental

Arm Description

SinnoTest® is a therapeutic guidance device for patients suffering from rheumatoid arthritis. Prescription of an original or biosimilar biotherapy (rituximab, adalimumab, abatacept) is possible.

Arm Title

Current practice

Arm Type

Active Comparator

Arm Description

Prescription of biotherapy without the SinnoTest® software which corresponds to current practice (all biotherapies).

Intervention Type

Device

Intervention Name(s)

SinnoTest®

Intervention Description

The selection of the biotherapy is carried out based on the recommendations of SinnoTest®. This test categorizes the bDMARDs based on the probability of response. It will allow to prescribe both original molecules, as well as biosimilars, in an equivalent way. In the SinnoTest® arm, the investigator prescribes the treatment defined as the most effective by SinnoTest®, except in case of contraindication. If contraindicated, the investigator prescribes the second-choice treatment (if any) of SinnoTest® in terms of efficacy.

Intervention Type

Other

Intervention Name(s)

Biotherapy prescription without SinnoTest® software

Intervention Description

The rheumatologist will use the current guidelines of rheumatoid arthritis to choose the more adapted biotherapy treatment to the patient

Primary Outcome Measure Information:

Title

Incremental Cost Utility ratio at 6 months

Description

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Budget impact analysis at 6 and 12 months

Description

Time Frame

12 months

Title

Software's predictive model performance

Description

Sensitivity, Especificity, positve and negative preddicted values of the predictive models using the biomarkers will be assessed on the new clinical data from the 6-month trial.

Time Frame

6 months

Title

Description of the variation of the proteomic profile between M0 (biotherapy start date) and M6 (6 months visit)

Description

Based on shotgun and semiquantitative proteomics, the diferences between the proteomic profile at baseline and at M6 will be analyzed

Time Frame

Inclusion and 6 months

Other Pre-specified Outcome Measures:

Title

Incremental Cost Effectiveness ratio at 6 months

Description

This outcome will be calculated as the average differential cost per patient between both study arms (mean costs of the Sinnotest® Arm - mean costs of the Control Arm) divided by the diference in effectiveness between both study arms measured as the percentage of patients achieving a good clinical response in each study arm (% in the Sinnotest® Arm - % in the Control Arm). Good clinical response will be measured using the EULAR criteria of Good clinical response Cost will be considered from a Societal perspective, including both direct and indirect costs The ratio will be expressed in cost (2019 Euros) per increase in 1% of subjects achieving a Good Clinical Response, which represents the additional cost that will have to be spent to earn a healthy year of life rates of treatment-response patients associated respectively with the usual strategy without SinnoTest® and with the strategy with SinnoTest®

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients over 18 years old and under 70 years old, Patients with RA, defined according to the ACR / EULAR 2010 or ACR 1987 criteria, Patients failing a first anti-TNF, defined as: Ineffectiveness (which is defined as a DAS28-ESR ≥3.2 and an inadequate response to iTNF according to the usual rheumatologist, which generally includes one or more of the following conditions: persistent swollen and tender joints, persistence of disease activity according to the overall evaluation of the patient, high levels of acute phase reactants and/or dependence of analgesics, nonsteroidal anti-inflammatory drugs or corticosteroids); or Toxicity(defined as the appearance of any adverse event that the patient's rheumatologist relates to the medication and requires discontinuation), Effective contraception for patients of childbearing potential (oral contraceptive, intrauterine device, implant, spermicide, surgical sterilization or abstinence), Patients able to read and understand the modalities of the protocol, Patients who have dated and signed the informed consent form of the trial, Stability of treatments (no change) between the selection visit and the inclusion visit (M0). Exclusion Criteria: Patients with a contraindication to any bDMARD or methotrexate, Patients included in another therapeutic evaluation study during this trial, Surgical intervention programmed during the trial, Patients with difficulties in understanding the Spanish language, Patients cannot be followed up 6 months, Psychosocial instability incompatible with regular monitoring (homelessness, addictive behaviour, antecedent of psychiatric pathology or any other comorbidity that would make it impossible for free and informed consent or limit adherence to the protocol), Breastfeeding and/or pregnancy. Although there are bDMARD that can be used in pregnancy, since SinnoTest can recommend one that discourages this condition, it is decided to exclude the inclusion of pregnant women.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Luis Rodriguez-Rodriguez, MD, PhD

Phone

+34913303615

Ext

7560

lrrodriguez@salud.madrid.org

First Name & Middle Initial & Last Name or Official Title & Degree

Dalifer Freites Nuñez, MD

Phone

+34913303615

daliferdayanira.freites@salud.madrid.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Benjamín Fernández-Gutiérrez, MD, PhD

Organizational Affiliation

Hospital San Carlos, Madrid

Official's Role

Principal Investigator

Facility Information:

Facility Name

Hospital Universitario La Princesa

City

Madrid

ZIP/Postal Code

28006

Country

Spain

Individual Site Status

Active, not recruiting

Facility Name

Hospital Universitario Ramon y Cajal

City

Madrid

ZIP/Postal Code

28034

Country

Spain

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Mónica Vázquez-Díaz, MD, PhD

Facility Name

Hospital Universitario Clinico San Carlos

City

Madrid

ZIP/Postal Code

28040

Country

Spain

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Benjamin Fernandez-Gutierrez, MD, PhD

Phone

+34913303615

Ext

7803

bfernandez.hcsc@salud.madrid.org

First Name & Middle Initial & Last Name & Degree

Luis Rodriguez-Rodriguez, MD, PhD

Phone

+34913303615

Ext

7560

lrrodriguez@salud.madrid.org

First Name & Middle Initial & Last Name & Degree

Dalifer Freites Nuñez, MD

Facility Name

Hospital Universitario 12 de Octubre

City

Madrid

ZIP/Postal Code

28041

Country

Spain

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

José Luis Pablos Álvarez, MD, PhD

Facility Name

Hospital Universitario de La Paz

City

Madrid

ZIP/Postal Code

28046

Country

Spain

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Alejandro Balsa Criado, MD, PhD

12. IPD Sharing Statement

Citations:

PubMed Identifier

29885551

Citation

Nguyen MVC, Baillet A, Romand X, Trocme C, Courtier A, Marotte H, Thomas T, Soubrier M, Miossec P, Tebib J, Grange L, Toussaint B, Lequerre T, Vittecoq O, Gaudin P. Prealbumin, platelet factor 4 and S100A12 combination at baseline predicts good response to TNF alpha inhibitors in rheumatoid arthritis. Joint Bone Spine. 2019 Mar;86(2):195-201. doi: 10.1016/j.jbspin.2018.05.006. Epub 2018 Jun 6.

Results Reference

background

PubMed Identifier

30243783

Citation

Nguyen MVC, Adrait A, Baillet A, Trocme C, Gottenberg JE, Gaudin P. Identification of cartilage oligomeric matrix protein as biomarker predicting abatacept response in rheumatoid arthritis patients with insufficient response to a first anti-TNFalpha treatment. Joint Bone Spine. 2019 May;86(3):401-403. doi: 10.1016/j.jbspin.2018.09.005. Epub 2018 Sep 19. No abstract available.

Results Reference

background

PubMed Identifier

30919904

Citation

Baillet A, Trocme C, Romand X, Nguyen CMV, Courtier A, Toussaint B, Gaudin P, Epaulard O. Calprotectin discriminates septic arthritis from pseudogout and rheumatoid arthritis. Rheumatology (Oxford). 2019 Sep 1;58(9):1644-1648. doi: 10.1093/rheumatology/kez098.

Results Reference

background

PubMed Identifier

20100792

Citation

Baillet A, Trocme C, Berthier S, Arlotto M, Grange L, Chenau J, Quetant S, Seve M, Berger F, Juvin R, Morel F, Gaudin P. Synovial fluid proteomic fingerprint: S100A8, S100A9 and S100A12 proteins discriminate rheumatoid arthritis from other inflammatory joint diseases. Rheumatology (Oxford). 2010 Apr;49(4):671-82. doi: 10.1093/rheumatology/kep452. Epub 2010 Jan 25.

Results Reference

background

PubMed Identifier

18664547

Citation

Trocme C, Marotte H, Baillet A, Pallot-Prades B, Garin J, Grange L, Miossec P, Tebib J, Berger F, Nissen MJ, Juvin R, Morel F, Gaudin P. Apolipoprotein A-I and platelet factor 4 are biomarkers for infliximab response in rheumatoid arthritis. Ann Rheum Dis. 2009 Aug;68(8):1328-33. doi: 10.1136/ard.2008.093153. Epub 2008 Jul 29.

Results Reference

background

PubMed Identifier

32867830

Citation

Freites-Nunez D, Baillet A, Rodriguez-Rodriguez L, Nguyen MVC, Gonzalez I, Pablos JL, Balsa A, Vazquez M, Gaudin P, Fernandez-Gutierrez B. Efficacy, safety and cost-effectiveness of a web-based platform delivering the results of a biomarker-based predictive model of biotherapy response for rheumatoid arthritis patients: a protocol for a randomized multicenter single-blind active controlled clinical trial (PREDIRA). Trials. 2020 Aug 31;21(1):755. doi: 10.1186/s13063-020-04683-7.

Results Reference

derived

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Prediction Medical Device for Rheumatoid Arthritis (PREDIRA)

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