MyocarditisRAFALENCT03387540
Evaluation of Reporting of Immune Checkpoint Inhibitor Associated Cardio-vascular Adverse Reactions
An observational study of Myocarditis and Cardiac Complication, run by Groupe Hospitalier Pitie-Salpetriere at 1 site in France.
Trial summary
Immune checkpoint inhibitors (ICIs) might have high grade immune-related adverse events (irAEs) on the cardio-vascular system. This study investigates reports of cardio-vascular toxicity with treatment including anti-PD1, Anti-PDL-1, and Anti CTLA4 classes using the World Health Organization (WHO) database VigiBase. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myocarditis, Cardiac Complication
- What is being tested?
- ICI
- How many people
- 104 participants
- Where
- 1 siteFrance
- Study dates
- 2 Dec 2017to 31 Dec 2017
- How long will I take part?
- 2 Days
- 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 treated with an ICI for a cancer
Who may be able to join
- Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017
- Adverse event reported were including the MedDRA terms: Cardiac and vascular investigations (excl enzyme tests) (HLGT), Vascular disorders (SOC), Skeletal and cardiac muscle analyses (HLT), Sudden death (PT), Sudden cardiac death (PT), Cardiac disorders (SOC), Cardiac arrhythmias (HLGT), Cardiac disorder signs and symptoms (HLGT), Cardiac neoplasms (HLGT), Cardiac valve disorders (HLGT), Congenital cardiac disorders (HLGT), Coronary artery disorders (HLGT), Endocardial disorders (HLGT), Heart failures (HLGT), Myocardial disorders (HLGT), Pericardial disorders (HLGT)
- Patients treated with ICIs included in the ATC: Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC32).
Who cannot join
- Chronology not compatible between the drug and the toxicity
Trial locations and contacts
1 site in 1 country.
France1 site
AP-HP, Pitié-Salpêtrière Hospital, Department of Pharmacology, CIC-1421, Pharmacovigilance Unit, INSERM.
Paris, 75013
About this study
Official title: Evaluation of Reporting of Immune Checkpoint Inhibitor Associated Cardio-vascular Adverse Reactions Using International Pharmacovigilance Database
Immune checkpoint inhibitors (ICIs) might have high grade immune-related adverse events (irAEs) on the cardio-vascular system. This study investigates reports of cardio-vascular toxicity with treatment including anti-PD1, Anti-PDL-1, and Anti CTLA4 classes using the World Health Organization (WHO) database VigiBase.
Read the detailed description
ICIs have dramatically improved clinical outcomes in multiple cancer types and are increasingly being tested in earlier disease settings and used in combination. However, irAEs can occur. Here the investigators use VigiBase (http://www.vigiaccess.org/), the World Health Organization (WHO) database of individual safety case reports, to identify cases of cardiovascular adverse drug reaction following treatment with ICIs.
- Conditions
- Myocarditis, Cardiac Complication
- Being tested
- ICI
- Keywords
- Anti-PD-1, Anti-PD-L1, Anti CTLA-4, Immune checkpoint inhibitors
- Medical subject headings
- Myocarditis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ICIDrug
Immune checkpoint inhibitor targeting either PD-1, PD-L1 or CTLA-4, and included in the following list (ATC classification): Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC32).
| Study group | Role | What they receive |
|---|---|---|
| Myocarditis induced by Immune check point inhibitor | Case reported in the World Health Organization (WHO) of myocarditis of patient treated by ICI, with a chronology compatible with the drug toxicity Receives: Drug: ICI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cardio-vascular toxicity of ICIs.
Identification and report of the cardio-vascular toxicity of ICIs. The research includes the report with MedDRA terms: SOC Cardiac Disorders, SOC Vascular Disorders, Sudden death (PT), Cardiac and vascular investigations (excl enzyme tests) (HLGT), Skeletal and cardiac muscle analyses (HLT). Drugs investigated are ICIs: Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC32).
Measured: Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017
Secondary outcomes (6)
Causality assessment of reported cardiovascular events according to the WHO system
Measured: Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017
Description of the type of cardiotoxicity depending on the category of ICIs
Measured: Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017
Description of the duration of treatment when the toxicity happens (role of cumulative dose)
Measured: Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017
Description of the drug-drug interactions associated with adverse events
Measured: Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017
Description of the pathologies (cancer) for which the incriminated drugs have been prescribed
Measured: Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017
Description of the population of patients having a cardio-vascular adverse event
Measured: Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jan 2018
- Study start2 Dec 2017
- Primary completion4 Dec 2017
- Study completion31 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for MyocarditisStudies 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
- Observational
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Enrolment
- 104 participants (actual)
- Target duration
- 2 Days
Sponsor and investigators
- Lead sponsor
- Groupe Hospitalier Pitie-Salpetriere
- Sponsor type
- University, hospital or other
- Collaborators
- Institute of Cardiometabolism and Nutrition, France, Vanderbilt University, Vanderbilt University Medical Center
- Responsible party
- Principal investigator, Joe Elie Salem, Groupe Hospitalier Pitie-Salpetriere
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03387540
- Sponsor's protocol ID
- CIC1421-17-12
- Acronym
- RAFALE
- Status last verified
- Sep 2019
- First submitted
- 22 Dec 2017
- Last updated
- 26 Sep 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Dressler D, Potter H. Molecular mechanisms in genetic recombination. Annu Rev Biochem. 1982;51:727-61. doi: 10.1146/annurev.bi.51.070182.003455. No abstract available.
PubMed 6287923Moslehi JJ, Salem JE, Sosman JA, Lebrun-Vignes B, Johnson DB. Increased reporting of fatal immune checkpoint inhibitor-associated myocarditis. Lancet. 2018 Mar 10;391(10124):933. doi: 10.1016/S0140-6736(18)30533-6. No abstract available.
PubMed 29536852Moslehi JJ, Salem JE, Sosman JA, Lebrun-Vignes B, Johnson DB. Reporting of immune checkpoint inhibitor-associated myocarditis - Authors' reply. Lancet. 2018 Aug 4;392(10145):384-385. doi: 10.1016/S0140-6736(18)31556-3. No abstract available.
PubMed 30102170Salem JE, Manouchehri A, Moey M, Lebrun-Vignes B, Bastarache L, Pariente A, Gobert A, Spano JP, Balko JM, Bonaca MP, Roden DM, Johnson DB, Moslehi JJ. Cardiovascular toxicities associated with immune checkpoint inhibitors: an observational, retrospective, pharmacovigilance study. Lancet Oncol. 2018 Dec;19(12):1579-1589. doi: 10.1016/S1470-2045(18)30608-9. Epub 2018 Nov 12.
PubMed 30442497
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Reporting of Immune Checkpoint Inhibitor Associated Cardio-vascular Adverse Reactions Using International Pharmacovigilance Database
- ClinicalTrials.gov ID
- NCT03387540
- Acronym / sponsor ID
- RAFALE / CIC1421-17-12
- Conditions
- Myocarditis, Cardiac Complication
- Keywords
- Anti-PD-1, Anti-PD-L1, Anti CTLA-4, Immune checkpoint inhibitors
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 104 participants (actual)
- Lead sponsor
- Groupe Hospitalier Pitie-SalpetriereUniversity, hospital or other
- Collaborators
- Institute of Cardiometabolism and Nutrition, France, Vanderbilt University, Vanderbilt University Medical Center
- Study start
- 2 Dec 2017 (actual)
- Primary completion
- 4 Dec 2017 (actual)
- Study completion
- 31 Dec 2017 (actual)
- First posted
- 2 Jan 2018 (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.
Immune checkpoint inhibitors (ICIs) might have high grade immune-related adverse events (irAEs) on the cardio-vascular system. This study investigates reports of cardio-vascular toxicity with treatment including anti-PD1, Anti-PDL-1, and Anti CTLA4 classes using the World Health Organization (WHO) database VigiBase.
Detailed description
ICIs have dramatically improved clinical outcomes in multiple cancer types and are increasingly being tested in earlier disease settings and used in combination. However, irAEs can occur. Here the investigators use VigiBase (http://www.vigiaccess.org/), the World Health Organization (WHO) database of individual safety case reports, to identify cases of cardiovascular adverse drug reaction following treatment with ICIs.
Study design
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Target follow-up
- 2 Days
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Myocarditis induced by Immune check point inhibitor | – | Drug: ICICase reported in the World Health Organization (WHO) of myocarditis of patient treated by ICI, with a chronology compatible with the drug toxicity |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients treated with an ICI for a cancer
Key inclusion criteria (3 listed)
- Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017
- Adverse event reported were including the MedDRA terms: Cardiac and vascular investigations (excl enzyme tests) (HLGT), Vascular disorders (SOC), Skeletal and cardiac muscle analyses (HLT), Sudden death (PT), Sudden cardiac death (PT), Cardiac disorders (SOC), Cardiac arrhythmias (HLGT), Cardiac disorder signs and symptoms (HLGT), Cardiac neoplasms (HLGT), Cardiac valve disorders (HLGT), Congenital cardiac disorders (HLGT), Coronary artery disorders (HLGT), Endocardial disorders (HLGT), Heart failures (HLGT), Myocardial disorders (HLGT), Pericardial disorders (HLGT)
- Patients treated with ICIs included in the ATC: Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC32).
Key exclusion criteria (1 listed)
- Chronology not compatible between the drug and the toxicity
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 |
|---|---|---|
| ICIImmune checkpoint inhibitor targeting either PD-1, PD-L1 or CTLA-4, and included in the following list (ATC classification): Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC32). | Drug | Myocarditis induced by Immune check point inhibitor |
Primary outcome
Cardio-vascular toxicity of ICIs.
Time frame: Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017
Identification and report of the cardio-vascular toxicity of ICIs. The research includes the report with MedDRA terms: SOC Cardiac Disorders, SOC Vascular Disorders, Sudden death (PT), Cardiac and vascular investigations (excl enzyme tests) (HLGT), Skeletal and cardiac muscle analyses (HLT). Drugs investigated are ICIs: Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC32).
6 secondary outcomes
Causality assessment of reported cardiovascular events according to the WHO system
Time frame: Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017
Description of the type of cardiotoxicity depending on the category of ICIs
Time frame: Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017
Description of the duration of treatment when the toxicity happens (role of cumulative dose)
Time frame: Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017
Description of the drug-drug interactions associated with adverse events
Time frame: Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017
Description of the pathologies (cancer) for which the incriminated drugs have been prescribed
Time frame: Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017
Description of the population of patients having a cardio-vascular adverse event
Time frame: Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017
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 26 Sep 2019.
- Background: PubMed 6287923Dressler D, Potter H. Molecular mechanisms in genetic recombination. Annu Rev Biochem. 1982;51:727-61. doi: 10.1146/annurev.bi.51.070182.003455. No abstract available.
- Results publication: PubMed 29536852Moslehi JJ, Salem JE, Sosman JA, Lebrun-Vignes B, Johnson DB. Increased reporting of fatal immune checkpoint inhibitor-associated myocarditis. Lancet. 2018 Mar 10;391(10124):933. doi: 10.1016/S0140-6736(18)30533-6. No abstract available.
- Results publication: PubMed 30102170Moslehi JJ, Salem JE, Sosman JA, Lebrun-Vignes B, Johnson DB. Reporting of immune checkpoint inhibitor-associated myocarditis - Authors' reply. Lancet. 2018 Aug 4;392(10145):384-385. doi: 10.1016/S0140-6736(18)31556-3. No abstract available.
- Results publication: PubMed 30442497Salem JE, Manouchehri A, Moey M, Lebrun-Vignes B, Bastarache L, Pariente A, Gobert A, Spano JP, Balko JM, Bonaca MP, Roden DM, Johnson DB, Moslehi JJ. Cardiovascular toxicities associated with immune checkpoint inhibitors: an observational, retrospective, pharmacovigilance study. Lancet Oncol. 2018 Dec;19(12):1579-1589. doi: 10.1016/S1470-2045(18)30608-9. Epub 2018 Nov 12.
- Individual participant dataSharing planned: Undecided
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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?
An observational study of Myocarditis and Cardiac Complication, run by Groupe Hospitalier Pitie-Salpetriere at 1 site in France.
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 3 inclusion and 1 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 26 Sep 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 France. 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.
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?
Cardio-vascular toxicity of ICIs. (time frame: Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017). 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 NCT03387540, which also lists 4 linked publications.
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 26 Sep 2019.