PharmacogeneticsNCT05307718
Pharmacogenomics in Prediction of Cardiovascular Drugs Adverse Reaction
An observational study of Pharmacogenetics and Drug-Related Side Effects and Adverse Reactions, run by Clinical Hospital Centre Zagreb at 1 site in Croatia.
Trial summary
The research is planned as a prospective nested case-control study. The plan is to recruit about 1,200 consecutive subjects whose pharmacotherapy involves the drug(s) of interest within 4.5 years. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pharmacogenetics, Drug-Related Side Effects and Adverse Reactions, Cardiovascular Drugs
- What is being tested?
- Oral Anticoagulant, Direct-Acting
- Type of treatment
- Pill or oral medicine
- How many people
- 1,200 participants
- Where
- 1 siteCroatia
- Study dates
- 15 Dec 2020to 14 Dec 2025
- 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: The primary cohort is represented by subjects who have a new indication for the administration of a) new oral anticoagulants (NOAC); b) platelet aggregation inhibitors from the P2Y12 receptor antagonist group (clopidogrel, prasugrel, ticagrelor); c) an HMG-CoA reductase inhibitor (statins); for the purpose of treatment or prophylaxis for at least 3 months; as monotherapy or without restriction with respect to any other concomitant pharmacological therapy.
Who may be able to join
- age 18 years or older; b) a new indication for the administration of any of the medicinal products of primary interest (NOAC, clopidogrel, prasugrel, ticagrelor, statins) for which at least a 3-month administration is predicted; c) signed informed consent (for repeated evaluations and donation of blood samples for genetic and eventual pharmacokinetic analysis).
Who cannot join
- the existence of contraindications to the medicines of primary interest.
Trial locations and contacts
1 site in 1 country.
Croatia1 site, 1 recruiting
- Recruiting
UHC Zagreb
Zagreb, 10000
Tamara Bozina, PhD, +385 1 4566 777, tamara.bozina@mef.hr
Livija Šimičević, PhD, +385 1 2388 888, lsimicev@kbc-zagreb.hr
About this study
The research is planned as a prospective nested case-control study. The plan is to recruit about 1,200 consecutive subjects whose pharmacotherapy involves the drug(s) of interest within 4.5 years. The basic cohort - the subjects with the newly indicated indication for use: NOAC; platelet aggregation inhibitors from the P2Y12 receptor antagonist group; and HMG-CoA reductase inhibitors (statins); as monotherapy or without restriction with respect to any other concomitant pharmacotherapy. The ADRs will be analysed by CR by: age, gender, expectancy, severity, association, type (mechanism of event), and outcome, according to the classification of organ systems as well as association with the phenotype. Criteria for bleeding associated with the use of anticoagulant and antiplatelet therapy have been defined; as well as the myotoxicity and hepatotoxicity associated with statin therapy. Samples will be tested for biochemical, haematological, coagulation standard parameters and pharmacogenetic analyses of relevant genes depending on the used therapy. Pharmacogenetic analysis will be performed to genotype the polymorphisms of relevant pharmacogenes: Biological samples and clinical data will be anonymized plus all records of ADRs and other clinical variables will be protected. Possible drug-drug and drug-drug-gene interactions will be evaluated using the Clinical Decision Support System (CDSS) of Lexicomp, PharmGKB, the Flockhart Table, and other systems including panel consensus methods to determine the likelihood of an ADR being associated with drug interactions, and determine whether drug interactions contributed to the occurrence of ADRs to administered CV pharmacotherapy in subjects with variant pharmacogenes of interest (drug-drug-gene interaction). The overall project objective is to determine which pharmacogenes variants, together with clinical parameters, can be used as predictors of CV drug ADRs and are good candidates for inclusion in the clinical diagnostic panel for pre-emptive PGx testing.
- Being tested
- Oral Anticoagulant, Direct-Acting
- Keywords
- Pharmacogenetics; adverse drug reactions; statins; DOAK; platelet aggregation inhibitors
- Medical subject headings
- Drug-Related Side Effects and Adverse Reactions
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral Anticoagulant, Direct-ActingDrug
Also called HMG-CoA reductase inhibitors, platelet aggregation inhibitors from the P2Y12 receptor antagonist group
Newly indicated indication for use: DOAC; platelet aggregation inhibitors from the P2Y12 receptor antagonist group; and HMG-CoA reductase inhibitors (statins); as monotherapy or without restriction with respect to any other concomitant pharmacotherapy. Subjects will be followed up during regular visits.
| Study group | Role | What they receive |
|---|---|---|
| The basic cohort | The subjects with the newly indicated indication for use: NOAC; platelet aggregation inhibitors from the P2Y12 receptor antagonist group; and HMG-CoA reductase inhibitors (statins Receives: Drug: Oral Anticoagulant, Direct-Acting | |
| Cases | Cases will be subjects who have observed ADRs during follow-up: bleeding that meets the criteria of "major" or "non-major, clinically relevant bleeding (for anticoagulants and platelet aggregation inhibitors); muscle or liver lesions (for statins); any other serious ADR. Receives: Drug: Oral Anticoagulant, Direct-Acting | |
| Controls | Controls will be subjects in whom no ADRs were observed during the study Receives: Drug: Oral Anticoagulant, Direct-Acting |
What is being measured
The primary outcome is the main question the study is designed to answer.
The overall project objective is to determine which pharmacogenes variants, together with clinical parameters, can be used as predictors of CV drug ADRs
Measured: 4.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2022
- Study start15 Dec 2020
- Primary completion14 Dec 2025 (estimated)
- Study completion14 Dec 2025 (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 PharmacogeneticsStudies 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-control
- Time perspective
- Prospective
- Enrolment
- 1,200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Clinical Hospital Centre Zagreb
- Sponsor type
- University, hospital or other
- Collaborators
- University of Zagreb, Croatian Science Foundation
- Responsible party
- Principal investigator, Livija Šimičević, Clinical Hospital Centre Zagreb
- Investigators
- Tamara Bozina, PhD, Principal investigator, University of Zagreb, Schooll of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05307718
- Sponsor's protocol ID
- UIP-2020-02-8189
- Status last verified
- Mar 2022
- First submitted
- 23 Mar 2022
- Last updated
- 1 Apr 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Bozina T, Ganoci L, Simicevic L, Vrkic Kirhmajer M, Mucalo I, Samardzic J, Palic J, Sliskovic AM, Trkulja V. Pharmacogenomics in the prediction of adverse effects of cardiovascular drugs: the PGx-CardioDrug project. Croat Med J. 2026 Jan 5;66(6):446-455. doi: 10.3325/cmj.2025.66.446.
PubMed 41520206
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacogenomics in Prediction of Cardiovascular Drugs Adverse Reaction
- ClinicalTrials.gov ID
- NCT05307718
- Acronym / sponsor ID
- UIP-2020-02-8189
- Keywords
- Pharmacogenetics; adverse drug reactions; statins; DOAK; platelet aggregation inhibitors
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 1,200 participants (estimated)
- Lead sponsor
- Clinical Hospital Centre ZagrebUniversity, hospital or other
- Collaborators
- University of Zagreb, Croatian Science Foundation
- Study start
- 15 Dec 2020 (actual)
- Primary completion
- 14 Dec 2025 (estimated)
- Study completion
- 14 Dec 2025 (estimated)
- First posted
- 1 Apr 2022 (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.
The research is planned as a prospective nested case-control study. The plan is to recruit about 1,200 consecutive subjects whose pharmacotherapy involves the drug(s) of interest within 4.5 years. The basic cohort - the subjects with the newly indicated indication for use: NOAC; platelet aggregation inhibitors from the P2Y12 receptor antagonist group; and HMG-CoA reductase inhibitors (statins); as monotherapy or without restriction with respect to any other concomitant pharmacotherapy. The ADRs will be analysed by CR by: age, gender, expectancy, severity, association, type (mechanism of event), and outcome, according to the classification of organ systems as well as association with the phenotype. Criteria for bleeding associated with the use of anticoagulant and antiplatelet therapy have been defined; as well as the myotoxicity and hepatotoxicity associated with statin therapy. Samples will be tested for biochemical, haematological, coagulation standard parameters and pharmacogenetic analyses of relevant genes depending on the used therapy. Pharmacogenetic analysis will be performed to genotype the polymorphisms of relevant pharmacogenes: Biological samples and clinical data will be anonymized plus all records of ADRs and other clinical variables will be protected. Possible drug-drug and drug-drug-gene interactions will be evaluated using the Clinical Decision Support System (CDSS) of Lexicomp, PharmGKB, the Flockhart Table, and other systems including panel consensus methods to determine the likelihood of an ADR being associated with drug interactions, and determine whether drug interactions contributed to the occurrence of ADRs to administered CV pharmacotherapy in subjects with variant pharmacogenes of interest (drug-drug-gene interaction). The overall project objective is to determine which pharmacogenes variants, together with clinical parameters, can be used as predictors of CV drug ADRs and are good candidates for inclusion in the clinical diagnostic panel for pre-emptive PGx testing.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| The basic cohort | – | Drug: Oral Anticoagulant, Direct-ActingThe subjects with the newly indicated indication for use: NOAC; platelet aggregation inhibitors from the P2Y12 receptor antagonist group; and HMG-CoA reductase inhibitors (statins |
| Cases | – | Drug: Oral Anticoagulant, Direct-ActingCases will be subjects who have observed ADRs during follow-up: bleeding that meets the criteria of "major" or "non-major, clinically relevant bleeding (for anticoagulants and platelet aggregation inhibitors); muscle or liver lesions (for statins); any other serious ADR. |
| Controls | – | Drug: Oral Anticoagulant, Direct-ActingControls will be subjects in whom no ADRs were observed during the study |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The primary cohort is represented by subjects who have a new indication for the administration of a) new oral anticoagulants (NOAC); b) platelet aggregation inhibitors from the P2Y12 receptor antagonist group (clopidogrel, prasugrel, ticagrelor); c) an HMG-CoA reductase inhibitor (statins); for the purpose of treatment or prophylaxis for at least 3 months; as monotherapy or without restriction with respect to any other concomitant pharmacological therapy.
Key inclusion criteria (1 listed)
- age 18 years or older; b) a new indication for the administration of any of the medicinal products of primary interest (NOAC, clopidogrel, prasugrel, ticagrelor, statins) for which at least a 3-month administration is predicted; c) signed informed consent (for repeated evaluations and donation of blood samples for genetic and eventual pharmacokinetic analysis).
Key exclusion criteria (1 listed)
- the existence of contraindications to the medicines of primary interest.
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 |
|---|---|---|
| Oral Anticoagulant, Direct-ActingAlso: HMG-CoA reductase inhibitors, platelet aggregation inhibitors from the P2Y12 receptor antagonist groupNewly indicated indication for use: DOAC; platelet aggregation inhibitors from the P2Y12 receptor antagonist group; and HMG-CoA reductase inhibitors (statins); as monotherapy or without restriction with respect to any other concomitant pharmacotherapy. Subjects will be followed up during regular visits. | Drug | Cases, Controls, The basic cohort |
Primary outcome
The overall project objective is to determine which pharmacogenes variants, together with clinical parameters, can be used as predictors of CV drug ADRs
Time frame: 4.5 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2022.
- Derived from this study: PubMed 41520206Bozina T, Ganoci L, Simicevic L, Vrkic Kirhmajer M, Mucalo I, Samardzic J, Palic J, Sliskovic AM, Trkulja V. Pharmacogenomics in the prediction of adverse effects of cardiovascular drugs: the PGx-CardioDrug project. Croat Med J. 2026 Jan 5;66(6):446-455. doi: 10.3325/cmj.2025.66.446.
- Project web siteLink provided by the sponsor.
- 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.
Tamara Bozina, PhD principal investigator
University of Zagreb, Schooll of Medicine
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 Pharmacogenetics and Drug-Related Side Effects and Adverse Reactions, run by Clinical Hospital Centre Zagreb at 1 site in Croatia.
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 1 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: status not confirmed, as of the sponsor's last update on 1 Apr 2022. 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 Croatia. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Tamara Bozina, PhD (+385 1 45 66 777, tamara.bozina@mef.hr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The overall project objective is to determine which pharmacogenes variants, together with clinical parameters, can be used as predictors of CV drug ADRs (time frame: 4.5 years). 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 NCT05307718, 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 1 Apr 2022; AzTrials last refreshed its copy on 8 Nov 2026.