Rheumatoid ArthritisPhase 4IDEANCT01308255
Infliximab as Induction Therapy in Early Rheumatoid Arthritis (IDEA)
A Phase 4 study testing Infliximab, Methylprednisolone and Methotrexate in people with Rheumatoid Arthritis, run by University of Leeds at 1 site in United Kingdom.
Trial summary
This is a placebo controlled randomised clinical trial.Patients attending Yorkshire Early Arthritis Clinics and diagnosed with rheumatoid arthritis with symptom duration of 3-12 months will be recruited. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Infliximab, Methylprednisolone and Methotrexate
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 112 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Sep 2006to Feb 2011
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men \& Women 18-80 years of age.
- Fulfil 1987 ACR criteria for RA.
- Symptoms of > 3 months and < 12 months duration.
- Men and women must use adequate birth control measures for the duration of the study and should continue such precautions for 6 months after receiving the last infusion or dose of methotrexate.
- The patient must be able to adhere to the study visit schedule and other protocol requirements.
- The patient must be capable of giving informed consent and the consent must be obtained prior to any screening procedures.
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- Must have a chest radiograph within 3 months prior to first treatment dose with no evidence of malignancy, infection or fibrosis.
- Are considered eligible according to the tuberculosis (TB) eligibility assessment.
- Active disease as defined by DAS > 2.4.
- TNF therapy naïve.
- DMARD therapy naïve.
- Negative hepatitis B and C screening tests within 3 months prior to screening.
Who cannot join
- Women who are pregnant, nursing, or men or women planning pregnancy within 24 months after screening.
- Use of any investigational (unlicensed) drug within 1 month prior to screening or within 5 half-lives of the investigational agent, whichever is longer.
- Previous or current treatment with any other therapeutic agent targeted at reducing TNF.
- Prior treatment with any DMARD.
- Serious infections (such as pneumonia or pyelonephritis) in the previous 3 months.
- Documented HIV infection.
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- Hepatitis- B or Hepatitis-C serology positive (must be checked within 3 months prior to screening).
- Are considered ineligible according to the TB eligibility assessment.
- Have or have had an opportunistic infection within 6 months prior to screening.
- Significant haematological or biochemical abnormality.
- Have current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease.
- Concomitant congestive heart failure, including medically controlled asymptomatic patients.
- Presence of a transplanted organ (with the exception of a corneal transplant > 3 months prior to screening).
- Malignancy within the past 5 years.
- History of lymphoproliferative disease including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease.
- Known recent substance abuse (drug or alcohol).
- Poor tolerability of venipuncture or lack of adequate venous access for required blood sampling during the study period.
- Have a chest radiograph at screening that shows evidence of malignancy, infection, or any abnormalities suggestive of TB.
- Have a positive Mantoux test or evidence of active TB infection, or recent close contact with an individual with active TB.
- Previous oral, IM, IA or IV corticosteroids within 1 month prior to baseline.
- Receiving treatment with anakinra.
- Contra-indications to methotrexate, infliximab or steroids.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Chapel Allerton Hospital
Leeds, West Yorkshire, LS7 4SA
About this study
Official title: A Multi-centre Randomised Double Blind Placebo Controlled Study Comparing Two Regimens of Combination Therapy in Early DMARD Naive Rheumatoid Arthritis.
This is a placebo controlled randomised clinical trial.Patients attending Yorkshire Early Arthritis Clinics and diagnosed with rheumatoid arthritis with symptom duration of 3-12 months will be recruited. They will be randomised to blinded therapy with either methotrexate and intravenous corticosteroid at baseline, or methotrexate and intravenous infliximab according to the standard treatment regime. Patients will be followed regularly, and at each visit, if the patients are not in remission, they will be given an intramuscular injection of corticosteroid. After 26 weeks, all patients will be unblinded and those with an inadequate treatment response will be treated according to a dose escalation algorithm until they achieve remission. Those in remission will continue on blinded therapy and if 6 months of remission is achieved the intravenous agent (infliximab or placebo) will be withdrawn.
Read the detailed description
The main aim of the study is to compare the efficacy of biologic therapy (infliximab) as induction therapy against current best practice therapy: early introduction of methotrexate in combination with steroid induction therapy and dose modification according to predefined disease activity measures (as informed by the literature, and based around a pragmatic dose escalation protocol).
Exploratory analyses of imaging findings will be undertaken on a subgroup of patients at sites able to perform such assessments.
The imaging techniques used include
- DEXA
- US
- Peripheral MRI
End point
The end points of the study are defined as:
- Completion of 78 weeks of therapy in the study
- Withdrawal due to any reason including toxicity or inefficacy
- Withdrawal due to completion of the dose escalation regime and disease remains active
- Withdrawal due to meeting NICE criteria for biologics during the dose escalation regime
At the end of the study, patients will continue to be followed in the Yorkshire Rheumatology clinics as part of their routine care.
All patients who withdraw will be asked to have a withdrawal visit with X-Rays of hands and feet to allow assessment of the primary endpoint.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Infliximab, Methylprednisolone, Methotrexate, Folic acid
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
InfliximabDrug
Also called Remicade
Prior to week 26
- Infliximab 3mg/kg standard regime (weeks 0, 2, 6, 14, 22)
- Methotrexate commencing at 10mg weekly, progressing to 20mg by week 6.
- Folic acid 5 mg daily except the day methotrexate is taken
Patients will be unblinded at week 26 and then treated pragmatically guided by disease activity
Also called Medrol, Solu-Medrol and Cadista.
Steroid
MethotrexateDrug
Also called Maxtrex
All patients enrolled are commenced on oral methotrexate 10mg once a week The methotrexate dose should be increased to 15 mg at the week 2 visit. The methotrexate should be increased to 20mg at the week 6 visit.
Folic acidDietary supplement
Also called vitamin B9,vitamin Bc, or folacin
All patients enrolled are commenced on oral folic acid 5mg daily, except the day methotrexate is taken, and the study infusions.
| Study group | Role | What they receive |
|---|---|---|
| Infliximab Arm | Experimental | For those randomised to the infliximab arm, infliximab will be administered at a dose of 3mg/kg according to the standard treatment protocol. Receives: Drug: Infliximab; Drug: Methotrexate; Dietary Supplement: Folic acid |
| Steroid/Placebo Arm | Placebo comparator | Patients randomised to this arm will receive an IV infusion of 250mg methylprednisolone at week 0 \& those without an adequate clinical response after 26 wks will receive additional steroid as IM methylprednisolone 120mg. Patients on this arm will receive an IV placebo infusion of 250ml of 9mg/l NaCl. Receives: Drug: Methylprednisolone; Drug: Methotrexate; Dietary Supplement: Folic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary endpoint is the change in Sharpe van der Heijde score
Measured: 50 Weeks
Secondary outcomes (9)
Number of patients having a major clinical response (DAS <1.6 for 6 months)
Measured: 78 Weeks
The change in Sharpe van der Heijde scores between baseline, 26 & 72 wk hand & feet x-rays
Measured: Week 72
The number of patients in clinical remission (DAS <1.6) at 78 weeks
Measured: 78 Weeks
The number of patients in infliximab free remission (DAS <1.6) at 78 weeks
Measured: 78 Weeks
The number of patients in clinical remission (DAS <1.6) at 26 weeks
Measured: 26 Weeks
RA Quality of Life questionnaire
Measured: 78 Weeks
Health Assessment Questionnaire
Measured: 78 Weeks
Immunogenetic studies to predict long-term immune response
Measured: 78 Weeks
Immune phenotyping (flow cytometry) and assessment of immune effector & regulatory functions
Measured: 78 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2011 (estimated)
- Study startSep 2006
- Primary completionFeb 2011
- Study completionFeb 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 112 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Leeds
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Paul Emery, University of Leeds
- Investigators
- Paul Emery, Principal investigator, University of Leeds
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01308255
- Sponsor's protocol ID
- RR05/7092
- Other IDs
- 2005-005013-37, 2005
- Acronym
- IDEA
- Status last verified
- Oct 2019
- First submitted
- 3 Mar 2011
- Last updated
- 1 Nov 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-centre Randomised Double Blind Placebo Controlled Study Comparing Two Regimens of Combination Therapy in Early DMARD Naive Rheumatoid Arthritis.
- ClinicalTrials.gov ID
- NCT01308255
- Acronym / sponsor ID
- IDEA / RR05/7092
- Conditions
- Rheumatoid Arthritis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 112 participants (actual)
- Lead sponsor
- University of LeedsUniversity, hospital or other
- Study start
- Sep 2006
- Primary completion
- Feb 2011 (actual)
- Study completion
- Feb 2011 (actual)
- First posted
- 4 Mar 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a placebo controlled randomised clinical trial.Patients attending Yorkshire Early Arthritis Clinics and diagnosed with rheumatoid arthritis with symptom duration of 3-12 months will be recruited. They will be randomised to blinded therapy with either methotrexate and intravenous corticosteroid at baseline, or methotrexate and intravenous infliximab according to the standard treatment regime. Patients will be followed regularly, and at each visit, if the patients are not in remission, they will be given an intramuscular injection of corticosteroid. After 26 weeks, all patients will be unblinded and those with an inadequate treatment response will be treated according to a dose escalation algorithm until they achieve remission. Those in remission will continue on blinded therapy and if 6 months of remission is achieved the intravenous agent (infliximab or placebo) will be withdrawn.
Detailed description
The main aim of the study is to compare the efficacy of biologic therapy (infliximab) as induction therapy against current best practice therapy: early introduction of methotrexate in combination with steroid induction therapy and dose modification according to predefined disease activity measures (as informed by the literature, and based around a pragmatic dose escalation protocol).
Exploratory analyses of imaging findings will be undertaken on a subgroup of patients at sites able to perform such assessments.
The imaging techniques used include
- DEXA
- US
- Peripheral MRI
End point
The end points of the study are defined as:
- Completion of 78 weeks of therapy in the study
- Withdrawal due to any reason including toxicity or inefficacy
- Withdrawal due to completion of the dose escalation regime and disease remains active
- Withdrawal due to meeting NICE criteria for biologics during the dose escalation regime
At the end of the study, patients will continue to be followed in the Yorkshire Rheumatology clinics as part of their routine care.
All patients who withdraw will be asked to have a withdrawal visit with X-Rays of hands and feet to allow assessment of the primary endpoint.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Infliximab Arm | Experimental | Drug: Infliximab, Drug: Methotrexate, Dietary Supplement: Folic acidFor those randomised to the infliximab arm, infliximab will be administered at a dose of 3mg/kg according to the standard treatment protocol. |
| Steroid/Placebo Arm | Placebo comparator | Drug: Methylprednisolone, Drug: Methotrexate, Dietary Supplement: Folic acidPatients randomised to this arm will receive an IV infusion of 250mg methylprednisolone at week 0 \& those without an adequate clinical response after 26 wks will receive additional steroid as IM methylprednisolone 120mg. Patients on this arm will receive an IV placebo infusion of 250ml of 9mg/l NaCl. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Men \& Women 18-80 years of age.
- Fulfil 1987 ACR criteria for RA.
- Symptoms of > 3 months and < 12 months duration.
- Men and women must use adequate birth control measures for the duration of the study and should continue such precautions for 6 months after receiving the last infusion or dose of methotrexate.
- The patient must be able to adhere to the study visit schedule and other protocol requirements.
Key exclusion criteria (22 listed)
- Women who are pregnant, nursing, or men or women planning pregnancy within 24 months after screening.
- Use of any investigational (unlicensed) drug within 1 month prior to screening or within 5 half-lives of the investigational agent, whichever is longer.
- Previous or current treatment with any other therapeutic agent targeted at reducing TNF.
- Prior treatment with any DMARD.
- Serious infections (such as pneumonia or pyelonephritis) in the previous 3 months.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| InfliximabAlso: RemicadePrior to week 26 * Infliximab 3mg/kg standard regime (weeks 0, 2, 6, 14, 22) * Methotrexate commencing at 10mg weekly, progressing to 20mg by week 6. * Folic acid 5 mg daily except the day methotrexate is taken Patients will be unblinded at week 26 and then treated pragmatically guided by disease activity | Drug | Infliximab Arm |
| MethylprednisoloneAlso: Medrol, Solu-Medrol and Cadista.Steroid | Drug | Steroid/Placebo Arm |
| MethotrexateAlso: MaxtrexAll patients enrolled are commenced on oral methotrexate 10mg once a week The methotrexate dose should be increased to 15 mg at the week 2 visit. The methotrexate should be increased to 20mg at the week 6 visit. | Drug | Infliximab Arm, Steroid/Placebo Arm |
| Folic acidAlso: vitamin B9,vitamin Bc, or folacinAll patients enrolled are commenced on oral folic acid 5mg daily, except the day methotrexate is taken, and the study infusions. | Dietary supplement | Infliximab Arm, Steroid/Placebo Arm |
Primary outcome
The primary endpoint is the change in Sharpe van der Heijde score
Time frame: 50 Weeks
9 secondary outcomes
Number of patients having a major clinical response (DAS <1.6 for 6 months)
Time frame: 78 Weeks
The change in Sharpe van der Heijde scores between baseline, 26 & 72 wk hand & feet x-rays
Time frame: Week 72
The number of patients in clinical remission (DAS <1.6) at 78 weeks
Time frame: 78 Weeks
The number of patients in infliximab free remission (DAS <1.6) at 78 weeks
Time frame: 78 Weeks
The number of patients in clinical remission (DAS <1.6) at 26 weeks
Time frame: 26 Weeks
RA Quality of Life questionnaire
Time frame: 78 Weeks
Health Assessment Questionnaire
Time frame: 78 Weeks
Immunogenetic studies to predict long-term immune response
Time frame: 78 Weeks
Immune phenotyping (flow cytometry) and assessment of immune effector & regulatory functions
Time frame: 78 Weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul Emery principal investigator
University of Leeds
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Infliximab, Methylprednisolone and Methotrexate in people with Rheumatoid Arthritis, run by University of Leeds at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary endpoint is the change in Sharpe van der Heijde score (time frame: 50 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2019.