The Effect of Salicylate on Platelet Function in CKD (Chronic Kidney Disease) Patients Treated With Aranesp

Erythropoietin Adverse Reaction Clinical Trial

— EPOASA  

Official title:

The Effect of Low-dose Salicylate Treatment on Platelet Function in Patients With Renal Failure Treated With Darbepoetin Alfa

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04330729
• Other study ID #: REG-018-2018
• Status: Recruiting
• Phase: N/A
• Start date: April 15, 2020
• Est. completion date: December 31, 2026

Study information

• Verified date: December 2023
• Source: Zealand University Hospital
• Contact: Mette KOefoed, md
• Phone: 0045 93576330
• Email: mkof[@]regionsjaelland.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Chronic hemodialysis, peritoneal dialysis or CKD 5 treated conservatively

• aged 18-85

• indication for treatment with Erythropoiesis-stimulating agents (ESA)

Exclusion Criteria:

1. Known allergy to ASA

2. Known contraindication to ASA, e.g. recent bleeding episode.

3. 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.

4. Raised reticulocyte count

5. Current anticoagulant therapy, e.g. warfarin, ADP receptor inhibitor (excepting short-term anticoagulant therapy in connection with dialysis)

6. Short expected length of life

7. Inability to give informed consent

8. Expected non-compliance

9. Active cancer - except for non-melanoma skin-cancer

10. Iron deficiency (defined as a reticulocyte Hgb <1,8 fmol. Patients can be included when their iron deficiency has been cured. .

11. Change in ESA dosis >33,3% within previous 2 month

12. 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.

13. Stable Aranesp ® dose <20 µg/week.

Related Conditions & MeSH terms

• Erythropoietin Adverse Reaction

Intervention

Drug:
• Acetylsalicylic acid
Se arm description

Locations

Country	Name	City	State
Denmark	Medicinsk afdeling, SUH Roskilde	Roskilde

Sponsors (1)

Lead Sponsor	Collaborator
Zealand University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Thrombocytaggregometry	Multiplate induced with arachidonic acid, ADP (adenosine diphosphate) and TRAP (Thrombin receptor-activating peptid)	16 weeks
Secondary	D-dimer	D-dimer, (FEU mg/L)	16 weeks
Secondary	MPV	Mean platelet volume, (fL=femtoliters)	16 weeks
Secondary	Total platelet count	Total platelet count (units per milliliters)	16 weeks
Secondary	PDW	platelet distribution width (fL = femtoliters)	16 weeks
Secondary	IPC	immature platelet count (platelets/microliter)	16 weeks
Secondary	IPF	Immature platelet fraction (%)	16 weeks
Secondary	H-IPF	Highly immature platelet fraction (%)	16 weeks
Secondary	ROTEM	Thromboelastometry	16 weeks
Secondary	TGF-beta	Transforming growth factor beta	16 weeks
Secondary	sP-selectin	Soluble platelet selectin	16 weeks
Secondary	Thrombomodulin	Thrombomodulin	16 weeks