Ischemic Heart DiseasePhase 1/2RITA-MINCT03072199
Rituximab in Patients With Acute ST-elevation Myocardial Infarction Study
A Phase 1/2 study testing RiTUXimab Injection in people with Ischemic Heart Disease and Myocardial Infarction, run by Papworth Hospital NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
RITA-MI aims to develop of a novel therapeutic concept to target the immune response in patients with acute myocardial infarction (MI) by depleting B-cells with a single injection of Rituximab which is approved for clinical use in cancer, autoimmune disease and inflammatory conditions. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Ischemic Heart Disease, Myocardial Infarction, Inflammation
- What is being tested?
- RiTUXimab Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Jun 2017to 1 May 2021
- Phase
- Phase 1/2
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-75 years old
- Acute anterior (left anterior descending artery) STEMI and successful primary percutaneous coronary intervention (PCI) with stent implantation in the culprit lesion during the first 24h after onset of symptoms
Who cannot join
- A previous history of STEMI
- Cardiogenic shock (systolic blood pressure <80 mm Hg, unresponsive to fluids, or necessitating catecholamines), electrical instability or severe congestive heart failure
- Residual severe proximal bystander disease awaiting inpatient revascularisation
- Corrected QT interval (QTc) > 500 msecs using Bazett's formula
- Hematologic abnormalities (hemoglobin <10 g/dL or hematocrit <30%, platelet cell count of <100 x103/μL, white blood cell count <4 x103/μL)
- Hypogammaglobulinaemia (defined as <3g/L of IgG)
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- Renal failure (estimated GFR by the MDRD formula < 45 ml/min/1.73m2);
- Known hepatic failure or abnormal liver function tests at baseline (ALT > 2 x ULN).
- Active or recurrent hepatitis (type B).
- Known HIV infection
- Current or previous tuberculosis (Chest X-Ray)
- Current infections
- Presence or history in the previous five years of an ongoing cancer, except in situ cancer of the cervix or basal cell carcinoma
- Any oral or intravenous immunosuppressive treatment (other than concomitant 100 mg methylprednisolone), disease modifying drugs, or other immune modulatory monoclonal antibodies or immunodepleting therapy at any time
- Allergy to rituximab or one of its excipients
- Expected need for vaccination with a live attenuated vaccine during the study including incomplete vaccination courses.
- Known or suspected pregnancy at screening or lactating woman
- Women of childbearing age unless confirmed by direct questioning that they are reproductively sterile or post-menopausal
- Participation in other clinical trials
- Inability to comply with study procedures
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Papworth Hospital NHS Trust
Cambridge, Cambridgeshire, CB23 3RE
About this study
RITA-MI aims to develop of a novel therapeutic concept to target the immune response in patients with acute myocardial infarction (MI) by depleting B-cells with a single injection of Rituximab which is approved for clinical use in cancer, autoimmune disease and inflammatory conditions. The goal is to re-purpose the drug, and translate the discovery into benefit for patients at high risk of cardiovascular events. Rituximab is expected to limit infarction size and improve the healing process, as complementary to other therapeutic strategies.
The applicants intend to perform a clinical study in patients with acute myocardial infarction (MI). The objective is to find the optimal dose (lowest dose with highest biological efficacy and best safety profile) for peripheral blood B cell depletion during the first 6 days after injection, and selective molecular signatures associated with improved heart function through analysis of peripheral blood samples.
The study rationale is to decrease the inflammatory reaction upon tissue necrosis following heart muscle ischemia.
- Conditions
- Ischemic Heart Disease, Myocardial Infarction, Inflammation
- Being tested
- RiTUXimab Injection
- Keywords
- Rituximab, B cells
- Medical subject headings
- Myocardial Ischemia, Myocardial Infarction, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RiTUXimab InjectionDrug
Single dose of Rituximab given intravenously within 48hours of myocardial infarction
| Study group | Role | What they receive |
|---|---|---|
| Rituximab | Experimental | Not described Receives: Drug: RiTUXimab Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety - Review of Adverse Events and Serious Adverse Events;
Adverse and serious adverse events will be reviewed by daily history taking and clinical examination of patients whilst they are an inpatient. Subsequently patients will be followed up on discharge daily until day 6 with telephone follow up. On days 6, 14 and 6month patients will be assess again in an outpatient setting where adverse events will be documented. There is additional follow telephone follow up at day 30. After each group of 6 patients are recruited and infused with rituximab, an independent Data and Safety Monitoring Board will review the clinical and biological data and their side effect profile, including adverse events.
Measured: 6month
Safety - Clinically significant changes in biochemical and haematological markers
Biochemistry and haematology bloods will be taken daily after drug administration whilst an inpatient. Upon discharge bloods will be taken on days 6, 14 and 6month for further assessment. Any new abnormalities will be flagged. After each group of 6 patients are recruited and infused with rituximab, an independent Data and Safety Monitoring Board will review the clinical and biological data and their side effect profile, including adverse events.
Measured: 6month
Safety - Clinically significant ECG changes
Arrhythmia will be assess as patients will have continued cardiac monitoring whilst an inpatient. ECGs will be performed daily whilst an inpatient and also during outpatient attendance. QTc will be assessed using the Bazett formula. After each group of 6 patients are recruited and infused with rituximab, an independent Data and Safety Monitoring Board will review the clinical and biological data and their side effect profile, including adverse events.
Measured: 6month
Secondary outcomes (2)
B cells
Circulating B cells count before, immediately after administration (30 mins and 6 hours), and extended follow up (6 days, 14 days and 6months)
Measured: Days 0, 6, 14 and 6months
Cardiac biomarkers - Circulating inflammatory (hsCRP and IL6) and cardiovascular (BNP and Troponin) biomarkers.
These will be measure before the infusion and compared to after infusion on days 2, 6 and 6 months
Measured: Days 0, 2 and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2017
- Study start1 Jun 2017
- Primary completion1 Mar 2019
- Study completion1 May 2021
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 Ischemic Heart DiseaseStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Phase 1/2 unblinded interventional dose escalation study
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Papworth Hospital NHS Foundation Trust
- Sponsor type
- Other government
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03072199
- Sponsor's protocol ID
- P02100
- Acronym
- RITA-MI
- Status last verified
- Sep 2021
- First submitted
- 24 Feb 2017
- Last updated
- 14 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Zhao TX, Aetesam-Ur-Rahman M, Sage AP, Victor S, Kurian R, Fielding S, Ait-Oufella H, Chiu YD, Binder CJ, Mckie M, Hoole SP, Mallat Z. Rituximab in patients with acute ST-elevation myocardial infarction: an experimental medicine safety study. Cardiovasc Res. 2022 Feb 21;118(3):872-882. doi: 10.1093/cvr/cvab113.
PubMed 33783498
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rituximab in Patients With Acute ST-elevation Myocardial Infarction Study
- ClinicalTrials.gov ID
- NCT03072199
- Acronym / sponsor ID
- RITA-MI / P02100
- Conditions
- Ischemic Heart Disease, Myocardial Infarction, Inflammation
- Keywords
- Rituximab, B cells
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Papworth Hospital NHS Foundation TrustOther government
- Study start
- 1 Jun 2017 (actual)
- Primary completion
- 1 Mar 2019 (actual)
- Study completion
- 1 May 2021 (actual)
- First posted
- 7 Mar 2017 (actual)
- 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.
RITA-MI aims to develop of a novel therapeutic concept to target the immune response in patients with acute myocardial infarction (MI) by depleting B-cells with a single injection of Rituximab which is approved for clinical use in cancer, autoimmune disease and inflammatory conditions. The goal is to re-purpose the drug, and translate the discovery into benefit for patients at high risk of cardiovascular events. Rituximab is expected to limit infarction size and improve the healing process, as complementary to other therapeutic strategies.
The applicants intend to perform a clinical study in patients with acute myocardial infarction (MI). The objective is to find the optimal dose (lowest dose with highest biological efficacy and best safety profile) for peripheral blood B cell depletion during the first 6 days after injection, and selective molecular signatures associated with improved heart function through analysis of peripheral blood samples.
The study rationale is to decrease the inflammatory reaction upon tissue necrosis following heart muscle ischemia.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Phase 1/2 unblinded interventional dose escalation study
| Arm | Type | Receives |
|---|---|---|
| Rituximab | Experimental | Drug: RiTUXimab Injection |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Age 18-75 years old
- Acute anterior (left anterior descending artery) STEMI and successful primary percutaneous coronary intervention (PCI) with stent implantation in the culprit lesion during the first 24h after onset of symptoms
Key exclusion criteria (20 listed)
- A previous history of STEMI
- Cardiogenic shock (systolic blood pressure <80 mm Hg, unresponsive to fluids, or necessitating catecholamines), electrical instability or severe congestive heart failure
- Residual severe proximal bystander disease awaiting inpatient revascularisation
- Corrected QT interval (QTc) > 500 msecs using Bazett's formula
- Hematologic abnormalities (hemoglobin <10 g/dL or hematocrit <30%, platelet cell count of <100 x103/μL, white blood cell count <4 x103/μL)
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 |
|---|---|---|
| RiTUXimab InjectionSingle dose of Rituximab given intravenously within 48hours of myocardial infarction | Drug | Rituximab |
Primary outcome
Safety - Review of Adverse Events and Serious Adverse Events;
Time frame: 6month
Adverse and serious adverse events will be reviewed by daily history taking and clinical examination of patients whilst they are an inpatient. Subsequently patients will be followed up on discharge daily until day 6 with telephone follow up. On days 6, 14 and 6month patients will be assess again in an outpatient setting where adverse events will be documented. There is additional follow telephone follow up at day 30. After each group of 6 patients are recruited and infused with rituximab, an independent Data and Safety Monitoring Board will review the clinical and biological data and their side effect profile, including adverse events.
Safety - Clinically significant changes in biochemical and haematological markers
Time frame: 6month
Biochemistry and haematology bloods will be taken daily after drug administration whilst an inpatient. Upon discharge bloods will be taken on days 6, 14 and 6month for further assessment. Any new abnormalities will be flagged. After each group of 6 patients are recruited and infused with rituximab, an independent Data and Safety Monitoring Board will review the clinical and biological data and their side effect profile, including adverse events.
Safety - Clinically significant ECG changes
Time frame: 6month
Arrhythmia will be assess as patients will have continued cardiac monitoring whilst an inpatient. ECGs will be performed daily whilst an inpatient and also during outpatient attendance. QTc will be assessed using the Bazett formula. After each group of 6 patients are recruited and infused with rituximab, an independent Data and Safety Monitoring Board will review the clinical and biological data and their side effect profile, including adverse events.
2 secondary outcomes
B cells
Time frame: Days 0, 6, 14 and 6months
Cardiac biomarkers - Circulating inflammatory (hsCRP and IL6) and cardiovascular (BNP and Troponin) biomarkers.
Time frame: Days 0, 2 and 6 months
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 14 Sep 2021.
- Derived from this study: PubMed 33783498Zhao TX, Aetesam-Ur-Rahman M, Sage AP, Victor S, Kurian R, Fielding S, Ait-Oufella H, Chiu YD, Binder CJ, Mckie M, Hoole SP, Mallat Z. Rituximab in patients with acute ST-elevation myocardial infarction: an experimental medicine safety study. Cardiovasc Res. 2022 Feb 21;118(3):872-882. doi: 10.1093/cvr/cvab113.
- Individual participant dataSharing planned: No
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing RiTUXimab Injection in people with Ischemic Heart Disease and Myocardial Infarction, run by Papworth Hospital NHS Foundation Trust 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 2 inclusion and 20 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 14 Sep 2021. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Safety - Review of Adverse Events and Serious Adverse Events; (time frame: 6month). The study lists 3 primary outcomes in all. 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 NCT03072199, 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 14 Sep 2021.