Erythropoietin Adverse ReactionEPOASANCT04330729
The Effect of Salicylate on Platelet Function in CKD (Chronic Kidney Disease) Patients Treated With Aranesp
A study testing Acetylsalicylic acid in people with Erythropoietin Adverse Reaction, run by Zealand University Hospital at 1 site in Denmark.
Trial summary
The aim of the study is to 1. To determine whether treatment with Erythropoiesis-stimulating agents (in the form of Aranesp®) affects platelet function, and how. 2. To determine whether salicylate treatment changes the effect of EPO (erythropoietin) on platelet function. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Erythropoietin Adverse Reaction
- What is being tested?
- Acetylsalicylic acid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteDenmark
- Study dates
- 15 Apr 2020to 31 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Chronic hemodialysis, peritoneal dialysis or CKD 5 treated conservatively
- aged 18-85
- indication for treatment with Erythropoiesis-stimulating agents (ESA)
Who cannot join
- Known allergy to ASA
- Known contraindication to ASA, e.g. recent bleeding episode.
- Known indication for ASA. If the patient is being treated with ASA, and the physician does not find any indication for this treatment, this can be stopped, and the patient included after 4 weeks.
- Raised reticulocyte count
- Current anticoagulant therapy, e.g. warfarin, ADP receptor inhibitor (excepting short-term anticoagulant therapy in connection with dialysis)
- Short expected length of life
Show all 13Show fewer
- Inability to give informed consent
- Expected non-compliance
- Active cancer - except for non-melanoma skin-cancer
- Iron deficiency (defined as a reticulocyte Hgb <1,8 fmol. Patients can be included when their iron deficiency has been cured. .
- Change in ESA dosis >33,3% within previous 2 month
- Fertile women. Pregnancy is excessively rare in dialysis patients. Women who are <50 years, or who are still menstruating will be excluded from the study.
- Stable Aranesp ® dose <20 µg/week.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Rikke Borg, md, phd contact
Denmark1 site, 1 recruiting
- Recruiting
Medicinsk afdeling, SUH Roskilde
Roskilde, 4000
Rikke Borg, phd, rbor@regionsjaelland.dk
Mette Koefoed, mkof@regionsjaelland.dk
About this study
Official title: The Effect of Low-dose Salicylate Treatment on Platelet Function in Patients With Renal Failure Treated With Darbepoetin Alfa
The aim of the study is to
- To determine whether treatment with Erythropoiesis-stimulating agents (in the form of Aranesp®) affects platelet function, and how.
- To determine whether salicylate treatment changes the effect of EPO (erythropoietin) on platelet function.
Read the detailed description
Background:
It is well known that treatment with EPO increases the risk of thrombotic complications in patients with chronic kidney disease, including cerebral thrombosis. The requited level of Hgb for sufficient treatment has therefore been set at a relatively low level (6.8-7.3 mM). One obvious potential cause of this problem is the increased thrombocytosis and platelet activation caused by EPO treatment. An old investigation has shown that low-dose acetyl salicylic acid (ASA) treatment can remove this effect. This investigation has not been performed using modern methods to investigate platelet function, and the possible prophylaxis of EPO-induced thrombosis has since received little interest.
Investigators of current study therefore propose to repeat this investigation using advanced methods for assessing thrombocyte function, as a preliminary, exploratory investigation prior to a later randomized controlled study.
Pre-treatment Washout (4 weeks, 6 weeks if treated with Mircera))
Patients who are not treated with ESA do not receive any treatment. Patients treated with ESA stop their treatment for 4 weeks. Patients treated with Mircera ® stop treatment for 6 weeks.
Patients must not take ASA as an analgesic during the whole period of the project.
At the end of the pre-treatment period, the Standard package (blood samples) is assessed.
EPO Treatment (4 weeks) The patient is treated with darbepoetin alfa (Aranesp) in equipotent doses compared to previous therapy.
After 2 weeks the Hgb is measured, and the EPO dosis adjusted if necessary at the discretion of the responsible physician.
After 4 weeks, the Standard package is assessed. If the Hgb is >8,0 mM or is rising rapidly (>1,2mM per month), the EPO dose is reduced at the discretion of the responsible physician.
EPO + ASA Treatment Aranesp treatment is supplemented with ASA (Hjertemagnyl ® 75 mg x 1 daily). After 4 weeks the Standard package is assessed.
If the patient develops gastrointestinal symptoms (abdominal pain, nausea or heartburn), and is not already being treated with pantoprazole or other PPI (proton pump inhibitors), treatment is supplemented with pantoprazole 40 mg x 1 daily.
ASA treatment withdrawal - e.g. in regard to surgery - results in discontinuation of participation in the study.
Post-treatment Washout Both Aranesp and Hjertemagnyl treatment is stopped. After 4 weeks the Standard package and is assessed.
Termination The indication for, and dose of ESA and ASA is prescribed at the discretion of the responsible physician.
- Conditions
- Erythropoietin Adverse Reaction
- Being tested
- Acetylsalicylic acid
- Keywords
- hemodialysis, platelet function, erythropoietin, thrombosis, anaemia
- Medical subject headings
- Thrombosis, Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Acetylsalicylic acidDrug
Se arm description
| Study group | Role | What they receive |
|---|---|---|
| Dialysis patients | Experimental | Patients will tablet acetylsalicylic acid 75mg x 1 for 4 weeks. Receives: Drug: Acetylsalicylic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Thrombocytaggregometry
Multiplate induced with arachidonic acid, ADP (adenosine diphosphate) and TRAP (Thrombin receptor-activating peptid)
Measured: 16 weeks
Secondary outcomes (11)
D-dimer
D-dimer, (FEU mg/L)
Measured: 16 weeks
MPV
Mean platelet volume, (fL=femtoliters)
Measured: 16 weeks
Total platelet count
Total platelet count (units per milliliters)
Measured: 16 weeks
PDW
platelet distribution width (fL = femtoliters)
Measured: 16 weeks
IPC
immature platelet count (platelets/microliter)
Measured: 16 weeks
IPF
Immature platelet fraction (%)
Measured: 16 weeks
H-IPF
Highly immature platelet fraction (%)
Measured: 16 weeks
ROTEM
Thromboelastometry
Measured: 16 weeks
TGF-beta
Transforming growth factor beta
Measured: 16 weeks
sP-selectin
Soluble platelet selectin
Measured: 16 weeks
Thrombomodulin
Thrombomodulin
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2020
- Study start15 Apr 2020
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Erythropoietin Adverse ReactionStudies of the same condition, open and under way.
- More trials run by Zealand University 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zealand University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- James G Heaf, Study director, Department of medicine, Zealand University Hospital, Denmark
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04330729
- Sponsor's protocol ID
- REG-018-2018
- Acronym
- EPOASA
- Status last verified
- Dec 2023
- First submitted
- 20 Mar 2020
- Last updated
- 25 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Low-dose Salicylate Treatment on Platelet Function in Patients With Renal Failure Treated With Darbepoetin Alfa
- ClinicalTrials.gov ID
- NCT04330729
- Acronym / sponsor ID
- EPOASA / REG-018-2018
- Conditions
- Erythropoietin Adverse Reaction
- Keywords
- hemodialysis, platelet function, erythropoietin, thrombosis, anaemia
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Zealand University HospitalUniversity, hospital or other
- Study start
- 15 Apr 2020 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 1 Apr 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.
The aim of the study is to
- To determine whether treatment with Erythropoiesis-stimulating agents (in the form of Aranesp®) affects platelet function, and how.
- To determine whether salicylate treatment changes the effect of EPO (erythropoietin) on platelet function.
Detailed description
Background:
It is well known that treatment with EPO increases the risk of thrombotic complications in patients with chronic kidney disease, including cerebral thrombosis. The requited level of Hgb for sufficient treatment has therefore been set at a relatively low level (6.8-7.3 mM). One obvious potential cause of this problem is the increased thrombocytosis and platelet activation caused by EPO treatment. An old investigation has shown that low-dose acetyl salicylic acid (ASA) treatment can remove this effect. This investigation has not been performed using modern methods to investigate platelet function, and the possible prophylaxis of EPO-induced thrombosis has since received little interest.
Investigators of current study therefore propose to repeat this investigation using advanced methods for assessing thrombocyte function, as a preliminary, exploratory investigation prior to a later randomized controlled study.
Pre-treatment Washout (4 weeks, 6 weeks if treated with Mircera))
Patients who are not treated with ESA do not receive any treatment. Patients treated with ESA stop their treatment for 4 weeks. Patients treated with Mircera ® stop treatment for 6 weeks.
Patients must not take ASA as an analgesic during the whole period of the project.
At the end of the pre-treatment period, the Standard package (blood samples) is assessed.
EPO Treatment (4 weeks) The patient is treated with darbepoetin alfa (Aranesp) in equipotent doses compared to previous therapy.
After 2 weeks the Hgb is measured, and the EPO dosis adjusted if necessary at the discretion of the responsible physician.
After 4 weeks, the Standard package is assessed. If the Hgb is >8,0 mM or is rising rapidly (>1,2mM per month), the EPO dose is reduced at the discretion of the responsible physician.
EPO + ASA Treatment Aranesp treatment is supplemented with ASA (Hjertemagnyl ® 75 mg x 1 daily). After 4 weeks the Standard package is assessed.
If the patient develops gastrointestinal symptoms (abdominal pain, nausea or heartburn), and is not already being treated with pantoprazole or other PPI (proton pump inhibitors), treatment is supplemented with pantoprazole 40 mg x 1 daily.
ASA treatment withdrawal - e.g. in regard to surgery - results in discontinuation of participation in the study.
Post-treatment Washout Both Aranesp and Hjertemagnyl treatment is stopped. After 4 weeks the Standard package and is assessed.
Termination The indication for, and dose of ESA and ASA is prescribed at the discretion of the responsible physician.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dialysis patients | Experimental | Drug: Acetylsalicylic acidPatients will tablet acetylsalicylic acid 75mg x 1 for 4 weeks. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Chronic hemodialysis, peritoneal dialysis or CKD 5 treated conservatively
- aged 18-85
- indication for treatment with Erythropoiesis-stimulating agents (ESA)
Key exclusion criteria (13 listed)
- Known allergy to ASA
- Known contraindication to ASA, e.g. recent bleeding episode.
- Known indication for ASA. If the patient is being treated with ASA, and the physician does not find any indication for this treatment, this can be stopped, and the patient included after 4 weeks.
- Raised reticulocyte count
- Current anticoagulant therapy, e.g. warfarin, ADP receptor inhibitor (excepting short-term anticoagulant therapy in connection with dialysis)
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 |
|---|---|---|
| Acetylsalicylic acidSe arm description | Drug | Dialysis patients |
Primary outcome
Thrombocytaggregometry
Time frame: 16 weeks
Multiplate induced with arachidonic acid, ADP (adenosine diphosphate) and TRAP (Thrombin receptor-activating peptid)
11 secondary outcomes
D-dimer
Time frame: 16 weeks
MPV
Time frame: 16 weeks
Total platelet count
Time frame: 16 weeks
PDW
Time frame: 16 weeks
IPC
Time frame: 16 weeks
IPF
Time frame: 16 weeks
H-IPF
Time frame: 16 weeks
ROTEM
Time frame: 16 weeks
TGF-beta
Time frame: 16 weeks
sP-selectin
Time frame: 16 weeks
Thrombomodulin
Time frame: 16 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jan 2024.
- Individual participant dataSharing planned: No
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.
Rikke Borg, md, phd contact
James G Heaf study director
Department of medicine, Zealand University Hospital, Denmark
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Acetylsalicylic acid in people with Erythropoietin Adverse Reaction, run by Zealand University Hospital at 1 site in Denmark.
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 13 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: looking for participants now, as of the sponsor's last update on 25 Jan 2024. 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 Denmark. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mette KOefoed, md (0045 93576330, mkof@regionsjaelland.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Thrombocytaggregometry (time frame: 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 25 Jan 2024.