Reumatoid ArthritisPOET-VEFNCT02130076
Interruption of TNFinhibitors and Endothelial Function
An observational study of Reumatoid Arthritis and Cardiovascular Diseases, run by Radboud University Medical Center.
Trial summary
Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular events. This increased risk is thought to be driven by inflammation-induced endothelial dysfunction, an initial step in atherogenesis. Treatment with TNFalpha inhibitors (TNFi) improve endothelial function in patients with RA. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Reumatoid Arthritis, Cardiovascular Diseases
- How many people
- 48 participants
- Where
- No sites listed yet
- Study dates
- Sep 2012to Dec 2014
- Phase
- Observational
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with stable rheumatoid arthritis who are included in another study (POEET) to stop or continue their TNFi therapy.
Who may be able to join
- Informed consent for POEET trial and this additional study
- On stable medication (except for TNFi-therapy)
Who cannot join
- Uncontrolled hypertension (RR > 140/90 mmHg average of three measurements at screening after 5 minutes of supine rest)
- Diabetes mellitus
- Heart failure or any other cardiovascular disease that is expected to induce changes in cardiovascular medication during the study period.
- Expected to start or change medication that can alter endothelial function (lipid lowering drugs, blood pressure lowering drugs, NSAIDs, immunosuppressive therapy other than TNFi drugs)
About this study
Official title: The Effect of Interruption of TNFi on Endothelial Function in Patients With Rheumatoid Arthritis
Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular events. This increased risk is thought to be driven by inflammation-induced endothelial dysfunction, an initial step in atherogenesis. Treatment with TNFalpha inhibitors (TNFi) improve endothelial function in patients with RA. Discontinuation of TNFi could therefore worsen endothelial function even in the absence of recurrence of systemic inflammation or reactivation of arthritis. If stopping TNFi results in worsening of endothelial function this would strongly suggest a higher cardiovascular risk in association with TNFi-wthdrawal
Read the detailed description
Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular events. This increased risk is thought to be driven by inflammation-induced endothelial dysfunction, an initial step in atherogenesis. Both systemic as well as local (intra-arterial) treatment with anti-TNF-antibody therapy improves endothelial function in patients with vasculitis or RA as reflected by the vasodilator response to intra-arterially infused acetylcholine. Also other vascular functions that are (at least partially) endothelium-dependent such as flow-mediated dilation of the brachial artery and pulse wave velocity are improved when active RA patients are being treated with methotrexate plus TNFi, i.e. infliximab or etanercept. ( Therefore one may hypothesize that when TNFi therapy is stopped, endothelial function may worsen even in the absence of recurrence of systemic inflammation or reactivation of arthritis. Endothelial function tests are a marker of long-term cardiovascular mortality. If stopping TNFi results in worsening of endothelial function this would strongly suggest a higher cardiovascular risk in association with TNFi-wthdrawal. These findings would indicate an important drawback for stopping TNFi in RA patients.
To date it is unclear whether the worsening of endothelial function occurs within half a year following the (successful) cessation of TNFi, whether this decline occurs simultaneously, or prior to RA exacerbation and whether this deterioration process is delayed by additional use of statin and/or ACEi.
To improve cardiovascular prognosis in RA significantly it is important to increase our knowledge regarding these processes.
- Conditions
- Reumatoid Arthritis, Cardiovascular Diseases
- Medical subject headings
- Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Stop | Patients with stable RA stopping TNF inhibition | |
| Continue | Patients with stable RA continuing TNFi therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response to acetylcholine
The primary endpoint is the interaction between TNFi-withdrawal and the vasodilator response to acetylcholine expressed as difference in FBF between the withdrawal group and the continuing group.
Measured: 6 months
Secondary outcomes (2)
TNFi withdrawal and response to nitroprusside
Secondary endpoints are the interaction between TNFi-withdrawal and the vasodilator response to nitroprusside (expressed as difference in FBF between the withdrawal group and the continuing group). The response to SNP serves as an internal vasodilator control to assess potential endothelium-independent effects of TNFi-withdrawal on the response to acetylcholine.
Measured: 6 months
VCAM and SCAM
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2014 (estimated)
- Study startSep 2012
- Primary completionDec 2014 (estimated)
- Study completionDec 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Reumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, G. Rongen, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02130076
- Sponsor's protocol ID
- IMM11-0103
- Acronym
- POET-VEF
- Status last verified
- Apr 2014
- First submitted
- 8 Jan 2013
- Last updated
- 2 May 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Rongen GA, van Ingen I, Kok M, Vonkeman H, Janssen M, Jansen TL. Vasodilator function worsens after cessation of tumour necrosis factor inhibitor therapy in patients with rheumatoid arthritis only if a flare occurs. Clin Rheumatol. 2018 Apr;37(4):909-916. doi: 10.1007/s10067-017-3961-6. Epub 2018 Jan 7.
PubMed 29307093
Study at a glance
From the registry record, last updated by the sponsor on 2 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Interruption of TNFi on Endothelial Function in Patients With Rheumatoid Arthritis
- ClinicalTrials.gov ID
- NCT02130076
- Acronym / sponsor ID
- POET-VEF / IMM11-0103
- Conditions
- Reumatoid Arthritis, Cardiovascular Diseases
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- Sep 2012
- Primary completion
- Dec 2014 (estimated)
- Study completion
- Dec 2014 (estimated)
- First posted
- 2 May 2014 (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.
Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular events. This increased risk is thought to be driven by inflammation-induced endothelial dysfunction, an initial step in atherogenesis. Treatment with TNFalpha inhibitors (TNFi) improve endothelial function in patients with RA. Discontinuation of TNFi could therefore worsen endothelial function even in the absence of recurrence of systemic inflammation or reactivation of arthritis. If stopping TNFi results in worsening of endothelial function this would strongly suggest a higher cardiovascular risk in association with TNFi-wthdrawal
Detailed description
Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular events. This increased risk is thought to be driven by inflammation-induced endothelial dysfunction, an initial step in atherogenesis. Both systemic as well as local (intra-arterial) treatment with anti-TNF-antibody therapy improves endothelial function in patients with vasculitis or RA as reflected by the vasodilator response to intra-arterially infused acetylcholine. Also other vascular functions that are (at least partially) endothelium-dependent such as flow-mediated dilation of the brachial artery and pulse wave velocity are improved when active RA patients are being treated with methotrexate plus TNFi, i.e. infliximab or etanercept. ( Therefore one may hypothesize that when TNFi therapy is stopped, endothelial function may worsen even in the absence of recurrence of systemic inflammation or reactivation of arthritis. Endothelial function tests are a marker of long-term cardiovascular mortality. If stopping TNFi results in worsening of endothelial function this would strongly suggest a higher cardiovascular risk in association with TNFi-wthdrawal. These findings would indicate an important drawback for stopping TNFi in RA patients.
To date it is unclear whether the worsening of endothelial function occurs within half a year following the (successful) cessation of TNFi, whether this decline occurs simultaneously, or prior to RA exacerbation and whether this deterioration process is delayed by additional use of statin and/or ACEi.
To improve cardiovascular prognosis in RA significantly it is important to increase our knowledge regarding these processes.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Stop | – | –Patients with stable RA stopping TNF inhibition |
| Continue | – | –Patients with stable RA continuing TNFi therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with stable rheumatoid arthritis who are included in another study (POEET) to stop or continue their TNFi therapy.
Key inclusion criteria (2 listed)
- Informed consent for POEET trial and this additional study
- On stable medication (except for TNFi-therapy)
Key exclusion criteria (4 listed)
- Uncontrolled hypertension (RR > 140/90 mmHg average of three measurements at screening after 5 minutes of supine rest)
- Diabetes mellitus
- Heart failure or any other cardiovascular disease that is expected to induce changes in cardiovascular medication during the study period.
- Expected to start or change medication that can alter endothelial function (lipid lowering drugs, blood pressure lowering drugs, NSAIDs, immunosuppressive therapy other than TNFi drugs)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Response to acetylcholine
Time frame: 6 months
The primary endpoint is the interaction between TNFi-withdrawal and the vasodilator response to acetylcholine expressed as difference in FBF between the withdrawal group and the continuing group.
2 secondary outcomes
TNFi withdrawal and response to nitroprusside
Time frame: 6 months
VCAM and SCAM
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 May 2014.
- Derived from this study: PubMed 29307093Rongen GA, van Ingen I, Kok M, Vonkeman H, Janssen M, Jansen TL. Vasodilator function worsens after cessation of tumour necrosis factor inhibitor therapy in patients with rheumatoid arthritis only if a flare occurs. Clin Rheumatol. 2018 Apr;37(4):909-916. doi: 10.1007/s10067-017-3961-6. Epub 2018 Jan 7.
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
An observational study of Reumatoid Arthritis and Cardiovascular Diseases, run by Radboud University Medical Center.
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 2 inclusion and 4 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: status not confirmed, as of the sponsor's last update on 2 May 2014. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
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?
Response to acetylcholine (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02130076, which also lists 1 linked publication.
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 2 May 2014.