Intracranial HemorrhagesRICHNCT02481011
Risk of Intracranial Hemorrhage in Users of Oral Antithrombotic Drugs
An observational study of Intracranial Hemorrhages and Stroke, run by St. Olavs Hospital at 1 site in Norway.
Trial summary
The true incidence and risks of intracranial hemorrhage (ICH) in patients on various antithrombotic treatments remain unknown. Here a nationwide study is conducted to investigate the risk for and incidence rates of ICH in users and non-users of various oral antithrombotic drugs in Norway between 2008 through 2014. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Intracranial Hemorrhages, Stroke
- What is being tested?
- antithrombotic drugs
- How many people
- 22,111 participants
- Where
- 1 siteNorway
- Study dates
- May 2015to 1 Jan 2016
- 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 intracranial hemorrhage admitted to hospitals in Norway 2008-2014
Who may be able to join
- hospitalization due to intracranial hemorrhage (ICH)
- residential address in Norway
Who cannot join
- Traumatic (high-energy) intracranial injury
- Parenteral antithrombotic treatment
- ICH related to tumor or vascular malformation
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Risk of Intracranial Hemorrhage in Users of Oral Antithrombotic Drugs: a Nationwide Study
The true incidence and risks of intracranial hemorrhage (ICH) in patients on various antithrombotic treatments remain unknown. Here a nationwide study is conducted to investigate the risk for and incidence rates of ICH in users and non-users of various oral antithrombotic drugs in Norway between 2008 through 2014.
Hopefully, this study will contribute to a more responsible prescription pattern of antithrombotic medications.
Read the detailed description
The most serious adverse effect of antithrombotic therapy is bleeding. Combinations of antithrombotic agents are now frequently used (e.g. after use of drug eluting stents or after ischemic stroke), and this may lead to an increased frequency of significant bleeding complications. Among hemorrhagic complications of antithrombotic drugs, intracranial hemorrhage (ICH) may have particularly devastating consequences with high morbidity, disability and even mortality rates. Intracerebral hemorrhage (hemorrhagic stroke) is generally associated with a higher risk for death and incurs greater loss of health over a lifetime than ischemic stroke.
This makes antithrombotic therapy a double-edged sword. Although a certain risk for bleeding may be acceptable in the context of even greater protection against ischemic events, it is important to quantify the magnitude of bleeding risk. So far the efficacy and safety profile of antithrombotic agents are generally assessed in randomized controlled trials (RCT). However, extrapolating the results from randomized clinical trials to the general patient population in this context is challenging. Patients who participate in clinical trials are frequently highly selected and therefore somewhat unrepresentative. In addition, their numbers are limited and the treatment period is often much shorter than in routine management of a chronic disease or condition. Finally, patients in clinical trials are often monitored more closely than in routine practice.
The incidence of intracranial hemorrhage due to antithrombotic therapy could theoretically be monitored by post-marketing surveillance by including spontaneously reported events. Unfortunately, it seems this does not provide more reliable estimates. A recent study from Finland has shown that bleeding complications due to oral anticoagulation with Warfarin are underreported in daily clinical practice. Further, it has been shown that reporting rates of side effects following medical therapy tend to decrease over time indicating that it is more likely that adverse events to a newer drug are reported than to a drug that has been available for many years. This is why population-based large-scale pharmaco-epidemiological studies are needed, in which cohorts of patients exposed to antithrombotic medications are monitored to determine a valid and reliable risk of the treatment.
- Conditions
- Intracranial Hemorrhages, Stroke
- Being tested
- antithrombotic drugs
- Keywords
- Fibrinolytic agents, Adverse effects, Registries, Incidence, Risk assessment
- Medical subject headings
- Intracranial Hemorrhages, Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
antithrombotic drugsDrug
| Study group | Role | What they receive |
|---|---|---|
| users | patients on antithrombotic drugs admitted to a Norwegian hospital for intracranial hemorrhage (ICH) Receives: Drug: antithrombotic drugs | |
| non-users | patients not on antithrombotic drugs admitted to a Norwegian hospital for intracranial hemorrhage (ICH) |
What is being measured
The primary outcome is the main question the study is designed to answer.
incidence rate of intracranial hemorrhage (ICH) requiring hospitalization
We will determine the incidence rates of ICH in users and non-users of oral antithrombotic treatment by linking data from Norwegian Patient Register (NPR) and the Norwegian prescription database.
Measured: 6 years
Secondary outcomes (2)
overall survival following ICH
comparison of users and non-users of oral antithrombotic drugs
Measured: 6 years
proportion of ICH patients undergoing neurosurgical procedures
comparison of users and non-users of oral antithrombotic drugs
Measured: 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2015 (estimated)
- Study startMay 2015
- Primary completion1 Jan 2016
- Study completion1 Jan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Intracranial HemorrhagesStudies of the same condition, open and under way.
- More trials run by St. Olavs 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
- Case only
- Time perspective
- Retrospective
- Enrolment
- 22,111 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Olavs Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Norwegian University of Science and Technology
- Responsible party
- Sponsor
- Investigators
- Sasha Gulati, md phd, Study director, Norwegian University of Science and Technology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02481011
- Sponsor's protocol ID
- 2014/7958
- Acronym
- RICH
- Status last verified
- Aug 2018
- First submitted
- 22 Jun 2015
- Last updated
- 28 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Gulati S, Solheim O, Carlsen SM, Oie LR, Jensberg H, Gulati AM, Giannadakis C, Jakola AS, Salvesen O. Risk of intracranial hemorrhage in users of oral antithrombotic drugs: Study protocol for a nationwide study. F1000Res. 2015 Dec 30;4:1519. doi: 10.12688/f1000research.7633.1. eCollection 2015.
PubMed 26918124Gulati S, Solheim O, Carlsen SM, Oie LR, Jensberg H, Gulati AM, Madsbu MA, Giannadakis C, Jakola AS, Salvesen O. Risk of intracranial hemorrhage (RICH) in users of oral antithrombotic drugs: Nationwide pharmacoepidemiological study. PLoS One. 2018 Aug 23;13(8):e0202575. doi: 10.1371/journal.pone.0202575. eCollection 2018.
PubMed 30138389
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Risk of Intracranial Hemorrhage in Users of Oral Antithrombotic Drugs: a Nationwide Study
- ClinicalTrials.gov ID
- NCT02481011
- Acronym / sponsor ID
- RICH / 2014/7958
- Conditions
- Intracranial Hemorrhages, Stroke
- Keywords
- Fibrinolytic agents, Adverse effects, Registries, Incidence, Risk assessment
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 22,111 participants (actual)
- Lead sponsor
- St. Olavs HospitalUniversity, hospital or other
- Collaborators
- Norwegian University of Science and Technology
- Study start
- May 2015 (actual)
- Primary completion
- 1 Jan 2016 (actual)
- Study completion
- 1 Jan 2016 (actual)
- First posted
- 25 Jun 2015 (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.
The true incidence and risks of intracranial hemorrhage (ICH) in patients on various antithrombotic treatments remain unknown. Here a nationwide study is conducted to investigate the risk for and incidence rates of ICH in users and non-users of various oral antithrombotic drugs in Norway between 2008 through 2014.
Hopefully, this study will contribute to a more responsible prescription pattern of antithrombotic medications.
Detailed description
The most serious adverse effect of antithrombotic therapy is bleeding. Combinations of antithrombotic agents are now frequently used (e.g. after use of drug eluting stents or after ischemic stroke), and this may lead to an increased frequency of significant bleeding complications. Among hemorrhagic complications of antithrombotic drugs, intracranial hemorrhage (ICH) may have particularly devastating consequences with high morbidity, disability and even mortality rates. Intracerebral hemorrhage (hemorrhagic stroke) is generally associated with a higher risk for death and incurs greater loss of health over a lifetime than ischemic stroke.
This makes antithrombotic therapy a double-edged sword. Although a certain risk for bleeding may be acceptable in the context of even greater protection against ischemic events, it is important to quantify the magnitude of bleeding risk. So far the efficacy and safety profile of antithrombotic agents are generally assessed in randomized controlled trials (RCT). However, extrapolating the results from randomized clinical trials to the general patient population in this context is challenging. Patients who participate in clinical trials are frequently highly selected and therefore somewhat unrepresentative. In addition, their numbers are limited and the treatment period is often much shorter than in routine management of a chronic disease or condition. Finally, patients in clinical trials are often monitored more closely than in routine practice.
The incidence of intracranial hemorrhage due to antithrombotic therapy could theoretically be monitored by post-marketing surveillance by including spontaneously reported events. Unfortunately, it seems this does not provide more reliable estimates. A recent study from Finland has shown that bleeding complications due to oral anticoagulation with Warfarin are underreported in daily clinical practice. Further, it has been shown that reporting rates of side effects following medical therapy tend to decrease over time indicating that it is more likely that adverse events to a newer drug are reported than to a drug that has been available for many years. This is why population-based large-scale pharmaco-epidemiological studies are needed, in which cohorts of patients exposed to antithrombotic medications are monitored to determine a valid and reliable risk of the treatment.
Study design
- Observational model
- Case only
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| users | – | Drug: antithrombotic drugspatients on antithrombotic drugs admitted to a Norwegian hospital for intracranial hemorrhage (ICH) |
| non-users | – | –patients not on antithrombotic drugs admitted to a Norwegian hospital for intracranial hemorrhage (ICH) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- patients with intracranial hemorrhage admitted to hospitals in Norway 2008-2014
Key inclusion criteria (2 listed)
- hospitalization due to intracranial hemorrhage (ICH)
- residential address in Norway
Key exclusion criteria (3 listed)
- Traumatic (high-energy) intracranial injury
- Parenteral antithrombotic treatment
- ICH related to tumor or vascular malformation
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 |
|---|---|---|
| antithrombotic drugs | Drug | users |
Primary outcome
incidence rate of intracranial hemorrhage (ICH) requiring hospitalization
Time frame: 6 years
We will determine the incidence rates of ICH in users and non-users of oral antithrombotic treatment by linking data from Norwegian Patient Register (NPR) and the Norwegian prescription database.
2 secondary outcomes
overall survival following ICH
Time frame: 6 years
proportion of ICH patients undergoing neurosurgical procedures
Time frame: 6 years
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 28 Aug 2018.
- Background: PubMed 26918124Gulati S, Solheim O, Carlsen SM, Oie LR, Jensberg H, Gulati AM, Giannadakis C, Jakola AS, Salvesen O. Risk of intracranial hemorrhage in users of oral antithrombotic drugs: Study protocol for a nationwide study. F1000Res. 2015 Dec 30;4:1519. doi: 10.12688/f1000research.7633.1. eCollection 2015.
- Results publication: PubMed 30138389Gulati S, Solheim O, Carlsen SM, Oie LR, Jensberg H, Gulati AM, Madsbu MA, Giannadakis C, Jakola AS, Salvesen O. Risk of intracranial hemorrhage (RICH) in users of oral antithrombotic drugs: Nationwide pharmacoepidemiological study. PLoS One. 2018 Aug 23;13(8):e0202575. doi: 10.1371/journal.pone.0202575. eCollection 2018.
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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.
Sasha Gulati, md phd study director
Norwegian University of Science and Technology
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 Intracranial Hemorrhages and Stroke, run by St. Olavs Hospital at 1 site in Norway.
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 3 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 28 Aug 2018. 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 Norway. 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?
incidence rate of intracranial hemorrhage (ICH) requiring hospitalization (time frame: 6 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 NCT02481011, which also lists 2 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 28 Aug 2018.