Aspirin ResistanceNCT00466154
The Effect of Serum LDL Lowering on Aspirin Resistance
A study testing Aspirin in people with Aspirin Resistance and Hypercholesterolemia, run by Ziv Hospital at 1 site in Israel.
Trial summary
Aspirin resistance is the persistent platelet activation, demonstrated by platelet function tests (1). The hypothesis is that:LDL lowering by statin in patients with aspirin resistance can improve the effect of aspirin due to the potential decreasing of cholesterol content in the platelet membranes. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Aspirin Resistance, Hypercholesterolemia
- What is being tested?
- Aspirin
- How many people
- 40 participants
- Where
- 1 siteIsrael
- Study dates
- Jul 2005to Jan 2007
- Phase
- Interventional
- 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Hypercholesterolemic low-moderate risk patients without hypolipidemic drugs for at least one month.
- Age ≥18 years on stable AHA step 1 diet.
- For primary prevention, LDL > 130 mg/dL and for secondary prevention LDL>70 and <100mg/dL. .
- CPK, ALT and AST < 1.5 x upper limit of normal at baseline.
Who cannot join
- Women currently receiving cyclical hormones.
- Treatment with hypolipidemic drugs during the last month.
- Oral corticosteroids, NSAID, COX-1 inhibitors and other antiplatelet drugs.
- Women with childbearing potential unless on safe contraception.
- Psychiatric disease with defect in judgement.
- Severe renal or hepatic diease.
- Uncontrolled hypo- or hyperthyroidism.
- Contraindication for ezetimibe or statin treatment.
Trial locations and contacts
1 site in 1 country.
Israel1 site
Internal Medicine Department A ,Ziv Goverment Hospital
Safed, 13110
About this study
Aspirin resistance is the persistent platelet activation, demonstrated by platelet function tests (1).
The hypothesis is that:LDL lowering by statin in patients with aspirin resistance can improve the effect of aspirin due to the potential decreasing of cholesterol content in the platelet membranes.
Patients and methods:Forty hypercholesterolemic patients with aspirin resistance after 5 days of treatment with aspirin and high LDL and triglycerides<300 mg/dL, will be enrolled.
Ten healthy volunteers will be the control group.
Read the detailed description
The patients will be treated by aspirin loading dose of 500mg and then 100 mg/day for other 4 days. For patients that will be entrolled in the regular working hours, platelet aggregation test and cholesterol content in platelet membranes will be done at baseline.
Blood tests for lipids, liver (ALT,AST,GGT,Alkaline phosphatase and bilirubin) and renal function tests (blood urea nitrogen and creatinine), complete blood count, general urine test and serum homocysteine will be done on the second day.
On the fifth day optical platelet aggregation test, cholesterol content in platelet membranes, platelet function in the PFA-100 system and soluble p-selectin in the plasma will be done If the patient has aspirin resistance (platelet aggregation 20% with epinephrine or 70% with ADP), LDL will be lowered in the plasma of 20 patients by hypolipidemic drugs (statin alone or combined with ezetimibe). Other 20 patients will continue to be treated by aspirin alone.
One month later, blood tests for lipids, liver (ALT,AST,GGT,Alkaline phosphatase and bilirubin) and renal function tests (blood urea nitrogen and creatinine), complete blood count, general urine test and serum homocysteine will be done for the second time and platelet activity will be tested again for all patients.
Platelet separation:
For platelet studies, venous blood (30 ml) will be collected through siliconized syringes into acid citrate dextrose solution(1.4% citric acid, 2.5% sodium citrate, and 2% dextrose) at a ratio of 9:1 (v:v) for washed platelets (WP)preparation.WP will be prepared by centrifugation at 240g for 20 min. The platelet bellet will be washed twice in 5 mmol Hepes buffer, pH 7.4 (140 mmol NaCl, 2 mmol KCL, 1 mmol MgCl2, 5 mmol Hepes, 12 mmol NaHCO3 and 5.5 mmol of glucose). For the preparation of WP suspension, 15 uL of acetic acid (1mmol) will be added to 1 ml of platelet suspension throughout WP preparation in order to ensure acidic conditions which are required for platelet resuspension. This procedure will reduce the medium pH to 6.5 and it does not influence the aggregation response of the WP.
Platelet aggregation:
Collagen (Nycomed, germany) will be used as the aggregating agent at a concentration of 4 ug/ml (this concentration can cause up to 60% aggregation amplitude in WP). Platelet aggregation will be perfomed at 37ºC in aggregometer using hepes as a reference system. Results will be expressed as the extent of maximal aggregation (% of maximal amplitude) and also as the slope of the aggregation curve (cm/min).
Cholesterol content in platelet membranes:
Platelets will be washed three times with Hepes buffer, and then sonicated twice for 20 seconds at 80 watt. Platelet lipids will be extracted with hexane:isopropanolol (3:2, v:v). The cholesterol content will be measured in the dried hexane phase by the method of Chiamori et al (12). Platelet protein will be determined using the method of Lowry (13).
- Conditions
- Aspirin Resistance, Hypercholesterolemia
- Being tested
- Aspirin
- Keywords
- Aspirin resistance, Platelet activation, Hypercholesterolemia
- Medical subject headings
- Hypercholesterolemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AspirinDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Spearsman's correlation coefficients will be calculated to determine the relation between changes in lipid parameters and changes in LDL tendency to oxidation and platelet aggregation.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2007 (estimated)
- Study startJul 2005
- Study completionJan 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Aspirin ResistanceStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants
Sponsor and investigators
- Lead sponsor
- Ziv Hospital
- Sponsor type
- Other government
- Investigators
- Osamah Hussein, MD, Principal investigator, Internal Medicine Department A, Ziv Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00466154
- Sponsor's protocol ID
- HP 5-173 S
- Status last verified
- Feb 2013
- First submitted
- 25 Apr 2007
- Last updated
- 20 Feb 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Sanderson S, Emery J, Baglin T, Kinmonth AL. Narrative review: aspirin resistance and its clinical implications. Ann Intern Med. 2005 Mar 1;142(5):370-80. doi: 10.7326/0003-4819-142-5-200503010-00012.
PubMed 15738456Kamath S, Blann AD, Lip GY. Platelet activation: assessment and quantification. Eur Heart J. 2001 Sep;22(17):1561-71. doi: 10.1053/euhj.2000.2515. No abstract available.
PubMed 11492985Bruno A, McConnell JP, Mansbach HH 3rd, Cohen SN, Tietjen GE, Bang NU. Aspirin and urinary 11-dehydrothromboxane B(2) in African American stroke patients. Stroke. 2002 Jan;33(1):57-60. doi: 10.1161/hs0102.102010.
PubMed 11779889Mammen EF, Comp PC, Gosselin R, Greenberg C, Hoots WK, Kessler CM, Larkin EC, Liles D, Nugent DJ. PFA-100 system: a new method for assessment of platelet dysfunction. Semin Thromb Hemost. 1998;24(2):195-202. doi: 10.1055/s-2007-995840.
PubMed 9579642Jefferson BK, Foster JH, McCarthy JJ, Ginsburg G, Parker A, Kottke-Marchant K, Topol EJ. Aspirin resistance and a single gene. Am J Cardiol. 2005 Mar 15;95(6):805-8. doi: 10.1016/j.amjcard.2004.11.045.
PubMed 15757620Reilly MP, Pratico D, Delanty N, DiMinno G, Tremoli E, Rader D, Kapoor S, Rokach J, Lawson J, FitzGerald GA. Increased formation of distinct F2 isoprostanes in hypercholesterolemia. Circulation. 1998 Dec 22-29;98(25):2822-8. doi: 10.1161/01.cir.98.25.2822.
PubMed 9860782Patrono C. Aspirin resistance: definition, mechanisms and clinical read-outs. J Thromb Haemost. 2003 Aug;1(8):1710-3. doi: 10.1046/j.1538-7836.2003.00284.x. No abstract available.
PubMed 12911581Cipollone F, Ciabattoni G, Patrignani P, Pasquale M, Di Gregorio D, Bucciarelli T, Davi G, Cuccurullo F, Patrono C. Oxidant stress and aspirin-insensitive thromboxane biosynthesis in severe unstable angina. Circulation. 2000 Aug 29;102(9):1007-13. doi: 10.1161/01.cir.102.9.1007.
PubMed 10961965Surya II, Akkerman JW. The influence of lipoproteins on blood platelets. Am Heart J. 1993 Jan;125(1):272-5. doi: 10.1016/0002-8703(93)90096-r. No abstract available.
PubMed 8380241Ardlie NG, Selley ML, Simons LA. Platelet activation by oxidatively modified low density lipoproteins. Atherosclerosis. 1989 Apr;76(2-3):117-24. doi: 10.1016/0021-9150(89)90094-4.
PubMed 2730708Osamah H, Mira R, Sorina S, Shlomo K, Michael A. Reduced platelet aggregation after fluvastatin therapy is associated with altered platelet lipid composition and drug binding to the platelets. Br J Clin Pharmacol. 1997 Jul;44(1):77-83. doi: 10.1046/j.1365-2125.1997.00625.x.
PubMed 9241100CHIAMORI N, HENRY RJ. Study of the ferric chloride method for determination of total cholesterol and cholesterol esters. Am J Clin Pathol. 1959 Apr;31(4):305-9. doi: 10.1093/ajcp/31.4.305. No abstract available.
PubMed 13637038LOWRY OH, ROSEBROUGH NJ, FARR AL, RANDALL RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265-75. No abstract available.
PubMed 14907713
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Serum LDL Lowering on Aspirin Resistance
- ClinicalTrials.gov ID
- NCT00466154
- Acronym / sponsor ID
- HP 5-173 S
- Conditions
- Aspirin Resistance, Hypercholesterolemia
- Keywords
- Aspirin resistance, Platelet activation, Hypercholesterolemia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants
- Lead sponsor
- Ziv HospitalOther government
- Study start
- Jul 2005
- Study completion
- Jan 2007 (actual)
- First posted
- 27 Apr 2007 (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.
Aspirin resistance is the persistent platelet activation, demonstrated by platelet function tests (1).
The hypothesis is that:LDL lowering by statin in patients with aspirin resistance can improve the effect of aspirin due to the potential decreasing of cholesterol content in the platelet membranes.
Patients and methods:Forty hypercholesterolemic patients with aspirin resistance after 5 days of treatment with aspirin and high LDL and triglycerides<300 mg/dL, will be enrolled.
Ten healthy volunteers will be the control group.
Detailed description
The patients will be treated by aspirin loading dose of 500mg and then 100 mg/day for other 4 days. For patients that will be entrolled in the regular working hours, platelet aggregation test and cholesterol content in platelet membranes will be done at baseline.
Blood tests for lipids, liver (ALT,AST,GGT,Alkaline phosphatase and bilirubin) and renal function tests (blood urea nitrogen and creatinine), complete blood count, general urine test and serum homocysteine will be done on the second day.
On the fifth day optical platelet aggregation test, cholesterol content in platelet membranes, platelet function in the PFA-100 system and soluble p-selectin in the plasma will be done If the patient has aspirin resistance (platelet aggregation 20% with epinephrine or 70% with ADP), LDL will be lowered in the plasma of 20 patients by hypolipidemic drugs (statin alone or combined with ezetimibe). Other 20 patients will continue to be treated by aspirin alone.
One month later, blood tests for lipids, liver (ALT,AST,GGT,Alkaline phosphatase and bilirubin) and renal function tests (blood urea nitrogen and creatinine), complete blood count, general urine test and serum homocysteine will be done for the second time and platelet activity will be tested again for all patients.
Platelet separation:
For platelet studies, venous blood (30 ml) will be collected through siliconized syringes into acid citrate dextrose solution(1.4% citric acid, 2.5% sodium citrate, and 2% dextrose) at a ratio of 9:1 (v:v) for washed platelets (WP)preparation.WP will be prepared by centrifugation at 240g for 20 min. The platelet bellet will be washed twice in 5 mmol Hepes buffer, pH 7.4 (140 mmol NaCl, 2 mmol KCL, 1 mmol MgCl2, 5 mmol Hepes, 12 mmol NaHCO3 and 5.5 mmol of glucose). For the preparation of WP suspension, 15 uL of acetic acid (1mmol) will be added to 1 ml of platelet suspension throughout WP preparation in order to ensure acidic conditions which are required for platelet resuspension. This procedure will reduce the medium pH to 6.5 and it does not influence the aggregation response of the WP.
Platelet aggregation:
Collagen (Nycomed, germany) will be used as the aggregating agent at a concentration of 4 ug/ml (this concentration can cause up to 60% aggregation amplitude in WP). Platelet aggregation will be perfomed at 37ºC in aggregometer using hepes as a reference system. Results will be expressed as the extent of maximal aggregation (% of maximal amplitude) and also as the slope of the aggregation curve (cm/min).
Cholesterol content in platelet membranes:
Platelets will be washed three times with Hepes buffer, and then sonicated twice for 20 seconds at 80 watt. Platelet lipids will be extracted with hexane:isopropanolol (3:2, v:v). The cholesterol content will be measured in the dried hexane phase by the method of Chiamori et al (12). Platelet protein will be determined using the method of Lowry (13).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Hypercholesterolemic low-moderate risk patients without hypolipidemic drugs for at least one month.
- Age ≥18 years on stable AHA step 1 diet.
- For primary prevention, LDL > 130 mg/dL and for secondary prevention LDL>70 and <100mg/dL. .
- CPK, ALT and AST < 1.5 x upper limit of normal at baseline.
Key exclusion criteria (8 listed)
- Women currently receiving cyclical hormones.
- Treatment with hypolipidemic drugs during the last month.
- Oral corticosteroids, NSAID, COX-1 inhibitors and other antiplatelet drugs.
- Women with childbearing potential unless on safe contraception.
- Psychiatric disease with defect in judgement.
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 |
|---|---|---|
| Aspirin | Drug | – |
Primary outcome
Spearsman's correlation coefficients will be calculated to determine the relation between changes in lipid parameters and changes in LDL tendency to oxidation and platelet aggregation.
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 20 Feb 2013.
- Background: PubMed 15738456Sanderson S, Emery J, Baglin T, Kinmonth AL. Narrative review: aspirin resistance and its clinical implications. Ann Intern Med. 2005 Mar 1;142(5):370-80. doi: 10.7326/0003-4819-142-5-200503010-00012.
- Background: PubMed 11492985Kamath S, Blann AD, Lip GY. Platelet activation: assessment and quantification. Eur Heart J. 2001 Sep;22(17):1561-71. doi: 10.1053/euhj.2000.2515. No abstract available.
- Background: PubMed 11779889Bruno A, McConnell JP, Mansbach HH 3rd, Cohen SN, Tietjen GE, Bang NU. Aspirin and urinary 11-dehydrothromboxane B(2) in African American stroke patients. Stroke. 2002 Jan;33(1):57-60. doi: 10.1161/hs0102.102010.
- Background: PubMed 9579642Mammen EF, Comp PC, Gosselin R, Greenberg C, Hoots WK, Kessler CM, Larkin EC, Liles D, Nugent DJ. PFA-100 system: a new method for assessment of platelet dysfunction. Semin Thromb Hemost. 1998;24(2):195-202. doi: 10.1055/s-2007-995840.
- Background: PubMed 15757620Jefferson BK, Foster JH, McCarthy JJ, Ginsburg G, Parker A, Kottke-Marchant K, Topol EJ. Aspirin resistance and a single gene. Am J Cardiol. 2005 Mar 15;95(6):805-8. doi: 10.1016/j.amjcard.2004.11.045.
- Background: PubMed 9860782Reilly MP, Pratico D, Delanty N, DiMinno G, Tremoli E, Rader D, Kapoor S, Rokach J, Lawson J, FitzGerald GA. Increased formation of distinct F2 isoprostanes in hypercholesterolemia. Circulation. 1998 Dec 22-29;98(25):2822-8. doi: 10.1161/01.cir.98.25.2822.
- Background: PubMed 12911581Patrono C. Aspirin resistance: definition, mechanisms and clinical read-outs. J Thromb Haemost. 2003 Aug;1(8):1710-3. doi: 10.1046/j.1538-7836.2003.00284.x. No abstract available.
- Background: PubMed 10961965Cipollone F, Ciabattoni G, Patrignani P, Pasquale M, Di Gregorio D, Bucciarelli T, Davi G, Cuccurullo F, Patrono C. Oxidant stress and aspirin-insensitive thromboxane biosynthesis in severe unstable angina. Circulation. 2000 Aug 29;102(9):1007-13. doi: 10.1161/01.cir.102.9.1007.
- Background: PubMed 8380241Surya II, Akkerman JW. The influence of lipoproteins on blood platelets. Am Heart J. 1993 Jan;125(1):272-5. doi: 10.1016/0002-8703(93)90096-r. No abstract available.
- Background: PubMed 2730708Ardlie NG, Selley ML, Simons LA. Platelet activation by oxidatively modified low density lipoproteins. Atherosclerosis. 1989 Apr;76(2-3):117-24. doi: 10.1016/0021-9150(89)90094-4.
- Background: PubMed 9241100Osamah H, Mira R, Sorina S, Shlomo K, Michael A. Reduced platelet aggregation after fluvastatin therapy is associated with altered platelet lipid composition and drug binding to the platelets. Br J Clin Pharmacol. 1997 Jul;44(1):77-83. doi: 10.1046/j.1365-2125.1997.00625.x.
- Background: PubMed 13637038CHIAMORI N, HENRY RJ. Study of the ferric chloride method for determination of total cholesterol and cholesterol esters. Am J Clin Pathol. 1959 Apr;31(4):305-9. doi: 10.1093/ajcp/31.4.305. No abstract available.
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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.
Osamah Hussein, MD principal investigator
Internal Medicine Department A, Ziv Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Aspirin in people with Aspirin Resistance and Hypercholesterolemia, run by Ziv Hospital at 1 site in Israel.
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 4 inclusion and 8 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 20 Feb 2013. 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 Israel. 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?
Spearsman's correlation coefficients will be calculated to determine the relation between changes in lipid parameters and changes in LDL tendency to oxidation and platelet aggregation.. 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 NCT00466154, which also lists 13 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 20 Feb 2013.