AntiplateletNCT04237935
Replication of the PLATO Antiplatelet Trial in Healthcare Claims Data
An observational study of Antiplatelet, run by Brigham and Women's Hospital at 1 site in United States.
Trial summary
Investigators are building an empirical evidence base for real world data through large-scale replication of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Antiplatelet
- What is being tested?
- Ticagrelor 90mg and Clopidogrel 75mg
- How many people
- 27,960 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Sep 2019to 18 Feb 2021
- 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 to 120 years
- All sexes
- Adult, Older adult
Study population: This study will involve a new user, parallel group, cohort study design comparing ticagrelor 90mg twice daily to clopidogrel 75mg daily. The patients will be required to have continuous enrollment during the baseline period of 180 days before initiation of ticagrelor 90mg or the comparator drug (cohort entry date). Follow-up for the outcome (3P-MACE), begins the day after drug initiation.
Who may be able to join
- 1-4 ALL REQUIRED
- 1. Hospitalized for potential ST-segment elevation or non-ST-segment elevation ACS, with onset during the previous 24 hours, documented by cardiac ischemic symptoms due to atherosclerosis of ≥10 minutes' duration at rest
- 2. ≥18 years of age
- 3. Not pregnant. Urinary and/or blood pregnancy tests are to be performed in women of child-bearing potential and repeated at least every 6 months. Women of child-bearing potential must be using ≥2 forms of reliable contraception, including one barrier method.
- 4. With informed consent 1-4 AND 5A OR 5B
- 5A. ≥2 of the following:
Show all 18Show fewer
- 1. ST-segment changes on ECG indicating ischemia. ST-segment depression or transient elevation ≥ 1 mm in two or more 2 contiguous leads"
- 2. Positive biomarker indicating myocardial necrosis. Troponin I or T or CK-MB greater than the upper limit of normal
- 3. One of the following:
- ≥60 y of age
- Previous MI or CABG
- CAD with ≥50% stenosis in ≥2 vessels
- Previous ischemic stroke, TIA (hospital-based diagnosis), carotid stenosis (≥50%), or cerebral revascularization
- Diabetes mellitus
- Peripheral artery disease
- Chronic renal dysfunction
- OR
- 5B. Persistent ST-segment elevation ≥1 mm (not known to be preexisting or due to a coexisting disorder) in ≥2 contiguous leads or new LBBB plus primary PCI planned.
Who cannot join
- Drug related
- 1. Contraindication to clopidogrel or other reason that study drug should not be administered (eg, hypersensitivity, moderate or severe liver disease, active bleeding or bleeding history, major surgery within 30 days)"
- 2. Oral anticoagulation therapy that cannot be stopped
- 3. Fibrinolytic therapy planned or within the previous 24 h
- 4. Concomitant oral or IV therapy with strong CYP3A inhibitors (ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, grapefruit juice N1 L/d), CYP3A substrates with narrow therapeutic indices (cyclosporine, quinidine), or strong CYP3A inducers (rifampin/rifampicin, phenytoin, carbamazepine)
- Treatment related
Show all 20Show fewer
- 1. Index event is an acute complication of PCI
- 2. PCI after index event and before first study dose
- Medical
- 1. Increased risk of bradycardiac events
- 2. Dialysis required
- 3. Known clinically important thrombocytopenia
- 4. Known clinically important anemia
- 5. Any other condition that may put the patient at risk or influence study results in the investigators' opinion (eg, cardiogenic shock, severe hemodynamic instability, active cancer)
- General
- 1. Participant in another investigational drug or device study within 30 days
- 2. Pregnancy or lactation
- 3. Any condition that increases the risk for noncompliance or being lost to follow-up
- 4. Involvement in the planning or conduct of the study
- 5. Previous enrollment or randomization in this study
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham And Women's Hospital
Boston, Massachusetts, 02120
About this study
Investigators are building an empirical evidence base for real world data through large-scale replication of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies.
Read the detailed description
This is a non-randomized, non-interventional study that is part of the RCT DUPLICATE initiative (www.rctduplicate.org) of the Brigham and Women's Hospital, Harvard Medical School. It is intended to replicate, as closely as is possible in healthcare insurance claims data, the trial listed below/above. Although many features of the trial cannot be directly replicated in healthcare claims, key design features, including outcomes, exposures, and inclusion/exclusion criteria, were selected to proxy those features from the trial. Randomization is also not replicable in healthcare claims data but was proxied through a statistical balancing of measured covariates according to standard practice. Investigators assume that the RCT provides the reference standard treatment effect estimate and that failure to replicate RCT findings is indicative of the inadequacy of the healthcare claims data for replication for a range of possible reasons and does not provide information on the validity of the original RCT finding.
- Conditions
- Antiplatelet
- Being tested
- Ticagrelor 90mg, Clopidogrel 75mg
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ticagrelor 90mgDrug
Ticagrelor 90 mg dispensing claim is used as the exposure group
Clopidogrel 75mgDrug
Clopidogrel 75 mg dispensing claim is used as the reference group
| Study group | Role | What they receive |
|---|---|---|
| Clopidogrel 75 mg | Reference group Receives: Drug: Clopidogrel 75mg | |
| Ticagrelor 90 mg | Exposure group Receives: Drug: Ticagrelor 90mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Relative hazard of 3-P MACE (composite outcome of Stroke, MI, and Mortality)
Relative hazard of 3-point major adverse cardiovascular events (MACE), i.e., non-fatal myocardial infarction, non-fatal stroke, or all-cause/CV mortality- Please refer to uploaded protocol for full definition due to size limitations.
Measured: Through study completion (a median of 163-219 days)
Secondary outcomes (3)
Relative hazard of Hospital admission for MI
Relative hazard of Hospital admission for MI - Please refer to uploaded protocol for full definition due to size limitations.
Measured: Through study completion (a median of 163-219 days)
Relative hazard of Hospital admission for stroke
Relative hazard of Hospital admission for stroke - Please refer to uploaded protocol for full definition due to size limitations.
Measured: Through study completion (a median of 163-219 days)
Relative hazard of All-cause mortality/CV mortality
Relative hazard of All-cause mortality/CV mortality- Please refer to uploaded protocol for full definition due to size limitations.
Measured: Through study completion (a median of 163-219 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2020
- Study start22 Sep 2019
- Primary completion18 Feb 2021
- Study completion18 Feb 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 AntiplateletStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe 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
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 27,960 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Shirley Vichy Wang, Brigham and Women's Hospital
- Investigators
- Shirley Wang, PhD, ScM, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04237935
- Sponsor's protocol ID
- 2018P002966-DUP-PLATO
- Status last verified
- Jul 2023
- First submitted
- 17 Jan 2020
- Last updated
- 27 Jul 2023
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Franklin JM, Patorno E, Desai RJ, Glynn RJ, Martin D, Quinto K, Pawar A, Bessette LG, Lee H, Garry EM, Gautam N, Schneeweiss S. Emulating Randomized Clinical Trials With Nonrandomized Real-World Evidence Studies: First Results From the RCT DUPLICATE Initiative. Circulation. 2021 Mar 9;143(10):1002-1013. doi: 10.1161/CIRCULATIONAHA.120.051718. Epub 2020 Dec 17.
PubMed 33327727
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Replication of the PLATO Antiplatelet Trial in Healthcare Claims Data
- ClinicalTrials.gov ID
- NCT04237935
- Acronym / sponsor ID
- 2018P002966-DUP-PLATO
- Conditions
- Antiplatelet
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 27,960 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Study start
- 22 Sep 2019 (actual)
- Primary completion
- 18 Feb 2021 (actual)
- Study completion
- 18 Feb 2021 (actual)
- First posted
- 23 Jan 2020 (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.
Investigators are building an empirical evidence base for real world data through large-scale replication of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies.
Detailed description
This is a non-randomized, non-interventional study that is part of the RCT DUPLICATE initiative (www.rctduplicate.org) of the Brigham and Women's Hospital, Harvard Medical School. It is intended to replicate, as closely as is possible in healthcare insurance claims data, the trial listed below/above. Although many features of the trial cannot be directly replicated in healthcare claims, key design features, including outcomes, exposures, and inclusion/exclusion criteria, were selected to proxy those features from the trial. Randomization is also not replicable in healthcare claims data but was proxied through a statistical balancing of measured covariates according to standard practice. Investigators assume that the RCT provides the reference standard treatment effect estimate and that failure to replicate RCT findings is indicative of the inadequacy of the healthcare claims data for replication for a range of possible reasons and does not provide information on the validity of the original RCT finding.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Clopidogrel 75 mg | – | Drug: Clopidogrel 75mgReference group |
| Ticagrelor 90 mg | – | Drug: Ticagrelor 90mgExposure group |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- This study will involve a new user, parallel group, cohort study design comparing ticagrelor 90mg twice daily to clopidogrel 75mg daily. The patients will be required to have continuous enrollment during the baseline period of 180 days before initiation of ticagrelor 90mg or the comparator drug (cohort entry date). Follow-up for the outcome (3P-MACE), begins the day after drug initiation.
Key inclusion criteria (18 listed)
- 1-4 ALL REQUIRED
- 5A. ≥2 of the following:
- OR
- 5B. Persistent ST-segment elevation ≥1 mm (not known to be preexisting or due to a coexisting disorder) in ≥2 contiguous leads or new LBBB plus primary PCI planned.
Key exclusion criteria (20 listed)
- Drug related
- Treatment related
- Medical
- General
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 |
|---|---|---|
| Ticagrelor 90mgTicagrelor 90 mg dispensing claim is used as the exposure group | Drug | Ticagrelor 90 mg |
| Clopidogrel 75mgClopidogrel 75 mg dispensing claim is used as the reference group | Drug | Clopidogrel 75 mg |
Primary outcome
Relative hazard of 3-P MACE (composite outcome of Stroke, MI, and Mortality)
Time frame: Through study completion (a median of 163-219 days)
Relative hazard of 3-point major adverse cardiovascular events (MACE), i.e., non-fatal myocardial infarction, non-fatal stroke, or all-cause/CV mortality- Please refer to uploaded protocol for full definition due to size limitations.
3 secondary outcomes
Relative hazard of Hospital admission for MI
Time frame: Through study completion (a median of 163-219 days)
Relative hazard of Hospital admission for stroke
Time frame: Through study completion (a median of 163-219 days)
Relative hazard of All-cause mortality/CV mortality
Time frame: Through study completion (a median of 163-219 days)
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 27 Jul 2023.
- Derived from this study: PubMed 33327727Franklin JM, Patorno E, Desai RJ, Glynn RJ, Martin D, Quinto K, Pawar A, Bessette LG, Lee H, Garry EM, Gautam N, Schneeweiss S. Emulating Randomized Clinical Trials With Nonrandomized Real-World Evidence Studies: First Results From the RCT DUPLICATE Initiative. Circulation. 2021 Mar 9;143(10):1002-1013. doi: 10.1161/CIRCULATIONAHA.120.051718. Epub 2020 Dec 17.
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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.
Shirley Wang, PhD, ScM principal investigator
Brigham and Women's Hospital
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 Antiplatelet, run by Brigham and Women's Hospital at 1 site in United States.
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 18 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 27 Jul 2023. 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 States. 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?
Relative hazard of 3-P MACE (composite outcome of Stroke, MI, and Mortality) (time frame: Through study completion (a median of 163-219 days)). 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 NCT04237935, 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 27 Jul 2023.