Chronic Kidney DiseasePhase 1WiCKDonASANCT01768637
Whole Blood Platelet Aggregation in Chronic Kidney Disease Patients on Aspirin Study
A Phase 1 study testing Aspirin and Clopidogrel in people with Chronic Kidney Disease, run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial summary
Higher coronary in-stent thromboses and bleeding complications on anti-platelet agents are more common in Chronic Kidney Disease vs. non-Chronic Kidney Disease patients. Poor inhibition of platelet aggregation by anti-platelet agents predicts future cardiovascular events. Read more about this study
- Who is it for?
- Ages 21 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Chronic Kidney Disease
- What is being tested?
- Aspirin and Clopidogrel
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2013to Jun 2014
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 21 to 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male or female >21 years
- Cases:
- Chronic kidney disease stages 4-5, with estimated glomerular filtration rate of <30
- Controls:
- estimated glomerular filtration rate of >90, urinary albumin to creatinine ratio <30 and no other kidney damage
Who cannot join
- End-stage renal disease (peritoneal dialysis and hemodialysis)
- Kidney transplant or any other transplant patient
- Recent hospitalizations <3 months
- Acute coronary or cerebrovascular event in the last 12 months
- Surgery in the last 3 months
- Blood dyscrasias or active bleeding
Show all 12Show fewer
- Gastro-intestinal bleeding in the last 6 months
- Concomitant use of other anti-platelet agent or antithrombotic drugs
- Recent treatment (<30 days) with a glycoprotein antagonist or proton pump inhibitor
- Hematocrit <25% or white blood cell count >20,000 or platelet count <50,000
- Any active malignancy or liver disease
- No current diagnosis of depression, not on any antidepressant medications,
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas Southwestern Medical Center
Dallas, Texas, 75390-8856
About this study
Official title: Whole Blood Platelet Aggregation in Chronic Kidney Disease Patients on Aspirin
Higher coronary in-stent thromboses and bleeding complications on anti-platelet agents are more common in Chronic Kidney Disease vs. non-Chronic Kidney Disease patients. Poor inhibition of platelet aggregation by anti-platelet agents predicts future cardiovascular events. Clinical practice guidelines are ambiguous about the use of these agents in Chronic Kidney Disease due to lack of controlled studies. The investigators hypothesize that patients with Chronic Kidney Disease compared with non-Chronic Kidney Disease have reduced platelet aggregation and poor platelet inhibitory response to aspirin. The aims are to 1) define the range of whole blood platelet aggregation in stages 3-5 Chronic Kidney Disease patients; 2) investigate whether patients with stages 4-5 Chronic Kidney Disease vs. non-Chronic Kidney Disease have lower platelet aggregation or impaired von Willebrand Factor activity; and 3) compare inhibition of platelet aggregation from baseline after 2 weeks of aspirin therapy and another 2 weeks of clopidogrel therapy added to aspirin in Chronic Kidney Disease vs. non-Chronic Kidney Disease patients. Accomplishing these aims will provide pilot data to power future studies of targeted anti-platelet agent treatments in Chronic Kidney Disease in order to improve cardiovascular outcomes.
Read the detailed description
Patients will be consented for the study and asked to initial on the consent form to state whether they agree for the genetic testing. After signing informed consent, complete medical history and medication list will be obtained and verified with the electronic medical record. After meeting all inclusion and exclusion criteria during the screening visit, those patients on aspirin for primary prevention of cardiovascular events will be asked to stop it for 2 weeks prior to blood collection for baseline data. Normal controls will be chosen after frequency matching for decade of age, gender, diabetes mellitus and interval of body mass index (5 kg/m2). Dietary supplements (Vitamin E and fish oil) known to affect platelet function will be assessed and patients on those will be asked to discontinue these. Participants with also be asked to not eat foods known to affect platelet function (coffee, chocolate, grapes, and alcohol) 48 hours prior to sample collection on visit 1. An interviewer-administered assessment of diet and exercise with a modified 24-hour dietary recall and the Stanford 7-day Physical activity Recall will be performed to ensure dietary consistency which may affect platelet aggregability on visit 1. Blood will be drawn via venopuncture for laboratory studies (whole blood platelet aggregation, von Willebrand Factor antigen levels and activity). Participants will be administered aspirin 81 mg for 2 weeks and asked to return in 2 weeks. On visit 2, whole blood platelet aggregation will be re-measured and questionnaires filled out. Two oral swabs will be taken from those participants who consented for genetic testing and samples will be stored at Dallas Veterans Affairs Medical Center for short term until shipped to Diagnostics Laboratory for genetic testing of clopidogrel cytochrome P450 polymorphisms. All participants will be administered clopidogrel 75 mg daily on top of aspirin 81 mg for 2 weeks and asked to return in 2 weeks. On visit 3, whole blood platelet aggregation will be re-measured and questionnaires filled out. At the completion of the study, participants will be placed back on their original antiplatelet agent if applicable and referred back to the primary care provider.
- Conditions
- Chronic Kidney Disease
- Being tested
- Aspirin, Clopidogrel
- Keywords
- Chronic kidney disease, Platelet function, aspirin, antiplatelet agent
- Medical subject headings
- Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AspirinDrug
Also called ASA
Aspirin 81 mg by mouth daily
ClopidogrelDrug
Also called Plavix
Clopidogrel 75 mg by mouth once daily
| Study group | Role | What they receive |
|---|---|---|
| Chronic Kidney Disease | Experimental | Patients with pre-dialysis stages 4-5 Chronic Kidney Disease will receive open-label aspirin 81 mg once daily for 2 weeks, then 2 weeks of aspirin 81 mg plus clopidogrel 75 mg once daily. Receives: Drug: Aspirin; Drug: Clopidogrel |
| Normal controls | Active comparator | Patients without Chronic Kidney Disease will receive open-label aspirin 81 mg once daily for 2 weeks, then 2 weeks of aspirin 81 mg plus clopidogrel 75 mg once daily. Receives: Drug: Aspirin; Drug: Clopidogrel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Whole Blood Platelet Aggregation to 0.5 Millimoles Arachidonic Acid
Citrated whole blood was used to measure platelet aggregation induced by agonist (arachidonic acid at 5 mM concentration) using impedance whole blood platelet aggregometry via a Chrono-log aggregometer. Values at baseline (visit 1) was compared between groups with post treatment values (visit 2) after 2 weeks of aspirin treatment
Measured: 2 weeks
Secondary outcomes (2)
Whole Blood Platelet Aggregation to 2 µg/mL Collagen
Citrated whole blood was used to measure platelet aggregation induced by agonist (collagen at 2mM concentration) using impedance whole blood platelet aggregometry via a Chrono-log aggregometer. Values at baseline (visit 1) was compared between groups with post treatment values (visit 2) after 2 weeks of aspirin treatment
Measured: 2 weeks
Whole Blood Platelet Aggregation to 20 µg/mL Adenosine Diphosphate
Citrated whole blood was used to measure platelet aggregation induced by agonist (adenosine diphosphate at 20mM concentration) using impedance whole blood platelet aggregometry via a Chrono-log aggregometer. Values at baseline (visit 1) and on aspirin (visit 2) was compared between groups with post treatment values (visit 3) after 2 weeks of aspirin and clopidogrel treatment
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2013 (estimated)
- Study startJan 2013
- Primary completionApr 2014
- Study completionJun 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Chronic Kidney DiseaseStudies of the same condition, open and under way.
- More trials run by University of Texas Southwestern Medical CenterThe 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- American Heart Association
- Responsible party
- Sponsor
- Investigators
- Susan Hedayati, MD, Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01768637
- Sponsor's protocol ID
- 12CRP11830004
- Acronym
- WiCKDonASA
- Status last verified
- Jan 2019
- First submitted
- 10 Jan 2013
- Last updated
- 19 Apr 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: we will upload informed consent form and the study protocol.
Publications
Jain N, Li X, Adams-Huet B, Sarode R, Toto RD, Banerjee S, Hedayati SS. Differences in Whole Blood Platelet Aggregation at Baseline and in Response to Aspirin and Aspirin Plus Clopidogrel in Patients With Versus Without Chronic Kidney Disease. Am J Cardiol. 2016 Feb 15;117(4):656-663. doi: 10.1016/j.amjcard.2015.11.029. Epub 2015 Dec 7.
PubMed 26725101Jain N, Wan F, Kothari M, Adelodun A, Ware J, Sarode R, Hedayati SS. Association of platelet function with depression and its treatment with sertraline in patients with chronic kidney disease: analysis of a randomized trial. BMC Nephrol. 2019 Oct 29;20(1):395. doi: 10.1186/s12882-019-1576-7.
PubMed 31664940
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Whole Blood Platelet Aggregation in Chronic Kidney Disease Patients on Aspirin
- ClinicalTrials.gov ID
- NCT01768637
- Acronym / sponsor ID
- WiCKDonASA / 12CRP11830004
- Conditions
- Chronic Kidney Disease
- Keywords
- Chronic kidney disease, Platelet function, aspirin, antiplatelet agent
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Collaborators
- American Heart Association
- Study start
- Jan 2013 (actual)
- Primary completion
- Apr 2014 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 15 Jan 2013 (estimated)
- Results
- Posted 19 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Higher coronary in-stent thromboses and bleeding complications on anti-platelet agents are more common in Chronic Kidney Disease vs. non-Chronic Kidney Disease patients. Poor inhibition of platelet aggregation by anti-platelet agents predicts future cardiovascular events. Clinical practice guidelines are ambiguous about the use of these agents in Chronic Kidney Disease due to lack of controlled studies. The investigators hypothesize that patients with Chronic Kidney Disease compared with non-Chronic Kidney Disease have reduced platelet aggregation and poor platelet inhibitory response to aspirin. The aims are to 1) define the range of whole blood platelet aggregation in stages 3-5 Chronic Kidney Disease patients; 2) investigate whether patients with stages 4-5 Chronic Kidney Disease vs. non-Chronic Kidney Disease have lower platelet aggregation or impaired von Willebrand Factor activity; and 3) compare inhibition of platelet aggregation from baseline after 2 weeks of aspirin therapy and another 2 weeks of clopidogrel therapy added to aspirin in Chronic Kidney Disease vs. non-Chronic Kidney Disease patients. Accomplishing these aims will provide pilot data to power future studies of targeted anti-platelet agent treatments in Chronic Kidney Disease in order to improve cardiovascular outcomes.
Detailed description
Patients will be consented for the study and asked to initial on the consent form to state whether they agree for the genetic testing. After signing informed consent, complete medical history and medication list will be obtained and verified with the electronic medical record. After meeting all inclusion and exclusion criteria during the screening visit, those patients on aspirin for primary prevention of cardiovascular events will be asked to stop it for 2 weeks prior to blood collection for baseline data. Normal controls will be chosen after frequency matching for decade of age, gender, diabetes mellitus and interval of body mass index (5 kg/m2). Dietary supplements (Vitamin E and fish oil) known to affect platelet function will be assessed and patients on those will be asked to discontinue these. Participants with also be asked to not eat foods known to affect platelet function (coffee, chocolate, grapes, and alcohol) 48 hours prior to sample collection on visit 1. An interviewer-administered assessment of diet and exercise with a modified 24-hour dietary recall and the Stanford 7-day Physical activity Recall will be performed to ensure dietary consistency which may affect platelet aggregability on visit 1. Blood will be drawn via venopuncture for laboratory studies (whole blood platelet aggregation, von Willebrand Factor antigen levels and activity). Participants will be administered aspirin 81 mg for 2 weeks and asked to return in 2 weeks. On visit 2, whole blood platelet aggregation will be re-measured and questionnaires filled out. Two oral swabs will be taken from those participants who consented for genetic testing and samples will be stored at Dallas Veterans Affairs Medical Center for short term until shipped to Diagnostics Laboratory for genetic testing of clopidogrel cytochrome P450 polymorphisms. All participants will be administered clopidogrel 75 mg daily on top of aspirin 81 mg for 2 weeks and asked to return in 2 weeks. On visit 3, whole blood platelet aggregation will be re-measured and questionnaires filled out. At the completion of the study, participants will be placed back on their original antiplatelet agent if applicable and referred back to the primary care provider.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Chronic Kidney Disease | Experimental | Drug: Aspirin, Drug: ClopidogrelPatients with pre-dialysis stages 4-5 Chronic Kidney Disease will receive open-label aspirin 81 mg once daily for 2 weeks, then 2 weeks of aspirin 81 mg plus clopidogrel 75 mg once daily. |
| Normal controls | Active comparator | Drug: Aspirin, Drug: ClopidogrelPatients without Chronic Kidney Disease will receive open-label aspirin 81 mg once daily for 2 weeks, then 2 weeks of aspirin 81 mg plus clopidogrel 75 mg once daily. |
Who may qualify
- Ages
- 21 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male or female >21 years
- Chronic kidney disease stages 4-5, with estimated glomerular filtration rate of <30
- estimated glomerular filtration rate of >90, urinary albumin to creatinine ratio <30 and no other kidney damage
Key exclusion criteria (12 listed)
- End-stage renal disease (peritoneal dialysis and hemodialysis)
- Kidney transplant or any other transplant patient
- Recent hospitalizations <3 months
- Acute coronary or cerebrovascular event in the last 12 months
- Surgery in the last 3 months
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 |
|---|---|---|
| AspirinAlso: ASAAspirin 81 mg by mouth daily | Drug | Chronic Kidney Disease, Normal controls |
| ClopidogrelAlso: PlavixClopidogrel 75 mg by mouth once daily | Drug | Chronic Kidney Disease, Normal controls |
Primary outcome
Whole Blood Platelet Aggregation to 0.5 Millimoles Arachidonic Acid
Time frame: 2 weeks
Citrated whole blood was used to measure platelet aggregation induced by agonist (arachidonic acid at 5 mM concentration) using impedance whole blood platelet aggregometry via a Chrono-log aggregometer. Values at baseline (visit 1) was compared between groups with post treatment values (visit 2) after 2 weeks of aspirin treatment
2 secondary outcomes
Whole Blood Platelet Aggregation to 2 µg/mL Collagen
Time frame: 2 weeks
Whole Blood Platelet Aggregation to 20 µg/mL Adenosine Diphosphate
Time frame: 4 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 26725101Jain N, Li X, Adams-Huet B, Sarode R, Toto RD, Banerjee S, Hedayati SS. Differences in Whole Blood Platelet Aggregation at Baseline and in Response to Aspirin and Aspirin Plus Clopidogrel in Patients With Versus Without Chronic Kidney Disease. Am J Cardiol. 2016 Feb 15;117(4):656-663. doi: 10.1016/j.amjcard.2015.11.029. Epub 2015 Dec 7.
- Derived from this study: PubMed 31664940Jain N, Wan F, Kothari M, Adelodun A, Ware J, Sarode R, Hedayati SS. Association of platelet function with depression and its treatment with sertraline in patients with chronic kidney disease: analysis of a randomized trial. BMC Nephrol. 2019 Oct 29;20(1):395. doi: 10.1186/s12882-019-1576-7.
- Individual participant dataSharing planned: Yes. we will upload informed consent form and the study protocol.
Related trials for Chronic Kidney Disease
Active, not recruitingPhase 2
Safety and Efficacy of Empagliflozin in Hemodialysis
End Stage Renal Disease
RecruitingPhase 3
Study to Assess the Efficacy, Pharmacokinetics, Safety and Tolerability of Atrasentan in Pediatric Patients With Primary IgAN
Berger Disease, Bergers Disease
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruiting
Hypothermic Kidney Machine Perfusion With Omnisol
End Stage Renal Disease (ESRD), Kidney Transplant
Not yet recruiting
An Individuation Intervention to Reduce Socioeconomic Disparities in Chronic Kidney Disease Care
Chronic Kidney Diseases
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.
Susan Hedayati, MD principal investigator
University of Texas Southwestern Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Aspirin and Clopidogrel in people with Chronic Kidney Disease, run by University of Texas Southwestern Medical Center at 1 site in United States.
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 5 inclusion and 12 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 19 Apr 2019. 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 United States. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Whole Blood Platelet Aggregation to 0.5 Millimoles Arachidonic Acid (time frame: 2 weeks). 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 NCT01768637, 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 19 Apr 2019.