SepsisPhase 2ASP-SEPSISNCT01784159
ASpirin for Patients With SEPsis and SeptIc Shock
A Phase 2 study testing Aspirin in people with Sepsis, run by Federal University of São Paulo at 1 site in Brazil.
Trial summary
This Randomized, pragmatic, multicentric with blinding of patients and health professionals, intention-to-treat analysis has by primary endpoint to evaluate whether the aspirin use reduces the intensity of organic dysfunction measured by the variation of the SOFA score starting from the day of admission to the seventh… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis
- What is being tested?
- Aspirin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 167 participants
- Where
- 1 siteBrazil
- Study dates
- 27 Mar 2019to 5 Jan 2023
- Phase
- Phase 2
- 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
Who may be able to join
- The three criteria below must be present:
- Signature of informed consent
- Patients must be older than 18 years old
- Diagnosis of sepsis and/or septic shock for less than 48 hours with at least one of the following organ dysfunctions:
- Lactate above 4mmol/L (36mg/dL)
- Thrombocytopenia < 100,000/mm3 or reduction > 50% in the count in the last 3 days
Show all 9Show fewer
- PaO2/FiO2 < 200 without signs of apparent volume overload
- Hypotension MAP < 65mmHg refractory to volume replacement with the need to use vasopressor
- Acute renal injury increased by 2.0 to 2.9 times from baseline or diuresis rate less than 0.5ml/kg/h for more than 12 hours
Who cannot join
- Pregnancy
- Impossibility to use the intestinal tract
- Death perspective in less than 24 hours
- Patients in the end of their lives or in exclusive palliative care
- Patients with active bleeding
- Prior study participation
Show all 17Show fewer
- Known allergy to aspirin
- Active peptic ulcer
- Previous use of antiplatelet agents in the last 7 days
- Previous use of AINEs in the last 7 days, except for dipyrone.
- Hemorrhagic stroke in the last 7 days or central nervous system surgery in the last 72 hours.
- Platelets <30,000 cells/mm3.
- Large surgery in the last 24 hours if the attending surgeon judges that the risk of bleeding is high enough that aspirin cannot be used.
- Ophthalmologic surgery postoperative and transurethral resection of the prostate at the discretion of the attending physician.
- Hepatic cirrhosis or previous liver disease with altered prothrombin activity, manifested by INR above 2.0 or other previous coagulopathies.
- Severe head injury in the last 7 days.
- Use or indication of anticoagulation
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Impact of Aspirin Use on the Severity of Organ Dysfunctions in Patients With Sepsis and Septic Shock: a Randomized, Double-blind, Placebo-controlled Trial - ASP-SEPSIS.
This Randomized, pragmatic, multicentric with blinding of patients and health professionals, intention-to-treat analysis has by primary endpoint to evaluate whether the aspirin use reduces the intensity of organic dysfunction measured by the variation of the SOFA score starting from the day of admission to the seventh day. Secundary endpoint: To evaluate if the aspirin use reduces the time of mechanical ventilation, length of stay in the ICU and in the hospital. In addition, to evaluate the safety of its administration regarding the occurrence of bleeding.
The data will be collected directly from the chart of the patients admitted to the ICU.
Read more
Data quality assurance will be made through periodic verification, aiming for complete and consistent data. The centers will receive periodic reports for adequacy of potentially inconsistent or incomplete data.
The baseline SOFA of patients with sepsis is 8.8 with a standard deviation of 3. The expected reduction in the control group in the SOFA at day 7 is 2 points. Considering a power of 80% and a level of significance of 0.05, it is estimated that 109 patients will be needed in each group. A total of 218 patients will compose the sample.
All analyzes will follow the intention-to-treat principle. We will evaluate the effect of aspirin compared to placebo on primary and binary outcomes by means of relative risks, 95% confidence intervals and chi-square tests. For continuous outcomes with normal distribution, we will present the mean difference, 95% confidence interval and P value calculated by t test. For continuous outcomes with asymmetric distribution, we will perform Wilcoxon test.
Read the detailed description
Design Randomized, pragmatic, multicentric with blinding of patients and health professionals.
Bias control Allocation secrecy with web randomization. Blinding of patients and health professionals. Intention-to-treat analysis.
Primary endpoint To evaluate whether the aspirin use reduces the intensity of organic dysfunction measured by the variation of the SOFA score starting from the day of admission to the seventh day.
Secondary endpoint To evaluate if the aspirin use reduces the time of mechanical ventilation, time with vasopressors, time in renal replacement therapy, length of stay in the ICU and in the hospital. In addition, to evaluate the safety of its administration regarding the occurrence of bleeding.
Eligibility
Inclusion criteria:
The three criteria below must be present:
- Signature of informed consent
- Patients must be older than 18 years old
- Diagnosis of sepsis and/or septic shock for less than 48 hours with at least one of the following organ dysfunctions:
- Lactate above 4mmol/L (36mg/dL)
- Thrombocytopenia < 100,000/mm3 or reduction > 50% in the count in the last 3 days
- PaO2/FiO2 < 200 without signs of apparent volume overload
- Hypotension MAP < 65mmHg refractory to volume replacement with the need to use vasopressor
Exclusion Criteria:
- Pregnancy
- Impossibility to use the intestinal tract
- Death perspective in less than 24 hours
- Patients in the end of their lives or in exclusive palliative care
- Patients with active bleeding
- Prior study participation
- Known allergy to aspirin
- Active peptic ulcer
- Previous use of antiplatelet agents in the last 7 days
- Previous use of AINEs in the last 7 days, except for dipyrone.
- Hemorrhagic stroke in the last 7 days or central nervous system surgery in the last 72 hours.
- Platelets <30,000 cells/mm3.
- Large surgery in the last 24 hours if the attending surgeon judges that the risk of bleeding is high enough that aspirin cannot be used.
- Ophthalmologic surgery postoperative and transurethral resection of the prostate at the discretion of the attending physician.
- Hepatic cirrhosis or previous liver disease with altered prothrombin activity, manifested by INR above 2.0 or other previous coagulopathies.
- Severe head injury in the last 7 days.
- Use or indication of anticoagulation.
Study intervention The treatments to be compared in the study are a dose of 200 mg of aspirin daily for 7 days and placebo. Both look identical.
Study outcomes
Primary outcomes:
- Variation of the SOFA score between D7 and D1
Secondary outcomes:
- Death in the ICU
- Days free of mechanical ventilation within 28 days
- Days free of vasopressor within 28 days
- Length of ICU stay
- Length of hospital stay
- Renal injury KDIGO >= 2 within 7 days
- Renal replacement therapy use
- Major bleeding occurency
- Count of unitis of red blood cells received in 14 days
Data management The data will be collected directly from the chart of the patients admitted to the ICU. Data quality assurance will be made through periodic verification, aiming for complete and consistent data. The centers will receive periodic reports for adequacy of potentially inconsistent or incomplete data.
Statistics The baseline SOFA of patients with sepsis is 8.8 with a standard deviation of 3. The expected reduction in the control group in the SOFA at day 7 is 2 points. Considering a power of 80% and a level of significance of 0.05, it is estimated that 109 patients will be needed in each group. A total of 218 patients will compose the sample.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AspirinDrug
Also called AAS
Aspirin administration for 7 days
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo 1tb / day/ 7days Receives: Drug: Aspirin |
| Aspirin | Active comparator | Intervention aspirin 200 mg/day for 7 days Receives: Drug: Aspirin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference between the Sequential Organ Failure Assessment (SOFA) Score on the seventh day of ICU stay and baseline (DeltaSOFA D7-D1).
To evaluate whether the aspirin use reduces the intensity of organic dysfunction. measured by the variation of the SOFA score starting from the day of admission to the seventh day. The Sequential Organ Failure Assessment (SOFA) Score ranges between 0 and 24.
Measured: 7 days
Secondary outcomes (5)
Mechanical ventilation free days;
To evaluate if the aspirin use reduces the time of mechanical ventilation, that ranges between 0 and 28 days.
Measured: 28 days
Vasopressor free days
To evaluate if the aspirin use reduces the days using vasoressors, that ranges between 0 and 28 days.
Measured: 28 days
Intensive Care Unit (ICU) free days
Length of stay in the ICU, that ranges between 0 and 28 days
Measured: 28 days
Hospital free days
Length of stay in the hospital, that ranges between 0 and 28 days
Measured: 28 days
Renal replacement therapy
Length of stay in renal replacement therapy, that ranges between 0 and 28 days
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2013 (estimated)
- Study start27 Mar 2019
- Primary completion15 Dec 2022
- Study completion5 Jan 2023
Why it stopped: Terminated: The study was stopped prematurely and will not be resumed due to the higher number of bleeding cases in the intervention group, as recomended by the Data Safety Monitoring Board on February 7, 2023.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SepsisStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 167 participants (actual)
Sponsor and investigators
- Lead sponsor
- Federal University of São Paulo
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Flavia Ribeiro Machado, Federal University of São Paulo
- Investigators
- Flavia Machado, Study chair, Federal University of São Paulo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01784159
- Sponsor's protocol ID
- EPM81449
- Acronym
- ASP-SEPSIS
- Status last verified
- Jul 2023
- First submitted
- 1 Feb 2013
- Last updated
- 13 Jul 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: undecided
Publications
Almeida TML, Freitas FGR, Figueiredo RC, Houly SG, Azevedo LCP, Cavalcanti AB, Damiani LP, Svicero BS, Souza MA, Bustamante CLS, Ramos FJS, Alves RSV, Atallah FC, Jackiu M, Pacheco ES, Schmidt RC, Serra FSC, Tomotani DYV, Zampieri FG, Machado FR; BRICNET. Acetylsalicylic Acid Treatment in Patients With Sepsis and Septic Shock: A Phase 2, Placebo-Controlled, Randomized Clinical Trial. Crit Care Med. 2025 Feb 1;53(2):e269-e281. doi: 10.1097/CCM.0000000000006564. Epub 2025 Feb 21.
PubMed 39982179
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Aspirin Use on the Severity of Organ Dysfunctions in Patients With Sepsis and Septic Shock: a Randomized, Double-blind, Placebo-controlled Trial - ASP-SEPSIS.
- ClinicalTrials.gov ID
- NCT01784159
- Acronym / sponsor ID
- ASP-SEPSIS / EPM81449
- Conditions
- Sepsis
- Keywords
- ICU, Sepsis, Aspirin, Septic shock
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated: The study was stopped prematurely and will not be resumed due to the higher number of bleeding cases in the intervention group, as recomended by the Data Safety Monitoring Board on February 7, 2023.
- Enrolment
- 167 participants (actual)
- Lead sponsor
- Federal University of São PauloUniversity, hospital or other
- Study start
- 27 Mar 2019 (actual)
- Primary completion
- 15 Dec 2022 (actual)
- Study completion
- 5 Jan 2023 (actual)
- First posted
- 5 Feb 2013 (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.
This Randomized, pragmatic, multicentric with blinding of patients and health professionals, intention-to-treat analysis has by primary endpoint to evaluate whether the aspirin use reduces the intensity of organic dysfunction measured by the variation of the SOFA score starting from the day of admission to the seventh day. Secundary endpoint: To evaluate if the aspirin use reduces the time of mechanical ventilation, length of stay in the ICU and in the hospital. In addition, to evaluate the safety of its administration regarding the occurrence of bleeding.
The data will be collected directly from the chart of the patients admitted to the ICU.
Data quality assurance will be made through periodic verification, aiming for complete and consistent data. The centers will receive periodic reports for adequacy of potentially inconsistent or incomplete data.
The baseline SOFA of patients with sepsis is 8.8 with a standard deviation of 3. The expected reduction in the control group in the SOFA at day 7 is 2 points. Considering a power of 80% and a level of significance of 0.05, it is estimated that 109 patients will be needed in each group. A total of 218 patients will compose the sample.
All analyzes will follow the intention-to-treat principle. We will evaluate the effect of aspirin compared to placebo on primary and binary outcomes by means of relative risks, 95% confidence intervals and chi-square tests. For continuous outcomes with normal distribution, we will present the mean difference, 95% confidence interval and P value calculated by t test. For continuous outcomes with asymmetric distribution, we will perform Wilcoxon test.
Detailed description
Design Randomized, pragmatic, multicentric with blinding of patients and health professionals.
Bias control Allocation secrecy with web randomization. Blinding of patients and health professionals. Intention-to-treat analysis.
Primary endpoint To evaluate whether the aspirin use reduces the intensity of organic dysfunction measured by the variation of the SOFA score starting from the day of admission to the seventh day.
Secondary endpoint To evaluate if the aspirin use reduces the time of mechanical ventilation, time with vasopressors, time in renal replacement therapy, length of stay in the ICU and in the hospital. In addition, to evaluate the safety of its administration regarding the occurrence of bleeding.
Eligibility
Inclusion criteria:
The three criteria below must be present:
- Signature of informed consent
- Patients must be older than 18 years old
- Diagnosis of sepsis and/or septic shock for less than 48 hours with at least one of the following organ dysfunctions:
- Lactate above 4mmol/L (36mg/dL)
- Thrombocytopenia < 100,000/mm3 or reduction > 50% in the count in the last 3 days
- PaO2/FiO2 < 200 without signs of apparent volume overload
- Hypotension MAP < 65mmHg refractory to volume replacement with the need to use vasopressor
Exclusion Criteria:
- Pregnancy
- Impossibility to use the intestinal tract
- Death perspective in less than 24 hours
- Patients in the end of their lives or in exclusive palliative care
- Patients with active bleeding
- Prior study participation
- Known allergy to aspirin
- Active peptic ulcer
- Previous use of antiplatelet agents in the last 7 days
- Previous use of AINEs in the last 7 days, except for dipyrone.
- Hemorrhagic stroke in the last 7 days or central nervous system surgery in the last 72 hours.
- Platelets <30,000 cells/mm3.
- Large surgery in the last 24 hours if the attending surgeon judges that the risk of bleeding is high enough that aspirin cannot be used.
- Ophthalmologic surgery postoperative and transurethral resection of the prostate at the discretion of the attending physician.
- Hepatic cirrhosis or previous liver disease with altered prothrombin activity, manifested by INR above 2.0 or other previous coagulopathies.
- Severe head injury in the last 7 days.
- Use or indication of anticoagulation.
Study intervention The treatments to be compared in the study are a dose of 200 mg of aspirin daily for 7 days and placebo. Both look identical.
Study outcomes
Primary outcomes:
- Variation of the SOFA score between D7 and D1
Secondary outcomes:
- Death in the ICU
- Days free of mechanical ventilation within 28 days
- Days free of vasopressor within 28 days
- Length of ICU stay
- Length of hospital stay
- Renal injury KDIGO >= 2 within 7 days
- Renal replacement therapy use
- Major bleeding occurency
- Count of unitis of red blood cells received in 14 days
Data management The data will be collected directly from the chart of the patients admitted to the ICU. Data quality assurance will be made through periodic verification, aiming for complete and consistent data. The centers will receive periodic reports for adequacy of potentially inconsistent or incomplete data.
Statistics The baseline SOFA of patients with sepsis is 8.8 with a standard deviation of 3. The expected reduction in the control group in the SOFA at day 7 is 2 points. Considering a power of 80% and a level of significance of 0.05, it is estimated that 109 patients will be needed in each group. A total of 218 patients will compose the sample.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: AspirinPlacebo 1tb / day/ 7days |
| Aspirin | Active comparator | Drug: AspirinIntervention aspirin 200 mg/day for 7 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Signature of informed consent
- Patients must be older than 18 years old
- Diagnosis of sepsis and/or septic shock for less than 48 hours with at least one of the following organ dysfunctions:
Key exclusion criteria (17 listed)
- Pregnancy
- Impossibility to use the intestinal tract
- Death perspective in less than 24 hours
- Patients in the end of their lives or in exclusive palliative care
- Patients with active bleeding
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: AASAspirin administration for 7 days | Drug | Aspirin, Placebo |
Primary outcome
Difference between the Sequential Organ Failure Assessment (SOFA) Score on the seventh day of ICU stay and baseline (DeltaSOFA D7-D1).
Time frame: 7 days
To evaluate whether the aspirin use reduces the intensity of organic dysfunction. measured by the variation of the SOFA score starting from the day of admission to the seventh day. The Sequential Organ Failure Assessment (SOFA) Score ranges between 0 and 24.
5 secondary outcomes
Mechanical ventilation free days;
Time frame: 28 days
Vasopressor free days
Time frame: 28 days
Intensive Care Unit (ICU) free days
Time frame: 28 days
Hospital free days
Time frame: 28 days
Renal replacement therapy
Time frame: 28 days
Results and safety
The study was stopped early (reason given: Terminated: The study was stopped prematurely and will not be resumed due to the higher number of bleeding cases in the intervention group, as recomended by the Data Safety Monitoring Board on February 7, 2023.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2023.
- Derived from this study: PubMed 39982179Almeida TML, Freitas FGR, Figueiredo RC, Houly SG, Azevedo LCP, Cavalcanti AB, Damiani LP, Svicero BS, Souza MA, Bustamante CLS, Ramos FJS, Alves RSV, Atallah FC, Jackiu M, Pacheco ES, Schmidt RC, Serra FSC, Tomotani DYV, Zampieri FG, Machado FR; BRICNET. Acetylsalicylic Acid Treatment in Patients With Sepsis and Septic Shock: A Phase 2, Placebo-Controlled, Randomized Clinical Trial. Crit Care Med. 2025 Feb 1;53(2):e269-e281. doi: 10.1097/CCM.0000000000006564. Epub 2025 Feb 21.
- Individual participant dataSharing planned: Undecided. undecided
Related trials for Sepsis
Not yet recruitingPhase 2/3
A Pivotal Safety and Immunogenicity GBS-NN/NN2 Vaccine Maternal Immunisation Trial
Streptococcus Agalactiae Infection, Neonatal Sepsis
Active, not recruiting
CT for Personalized Mechanical Ventilation
Ventilator-Induced Lung Injury, Sepsis Syndrome
RecruitingPhase 4
A Study to Compare the Efficacy and Safety of Extended and Intermittent Infusion of Beta-lactams in Critically Ill Paediatric Patients
Infection, Sepsis
Not yet recruiting
Double Plasma Separation and Adsorption in Acute-on-Chronic Liver Failure (DPMAS-ACLF Trial)
Acute-on-Chronic Liver Failure (ACLF)
Active, not recruitingPhase 4
Thymosin Alpha 1 and IgM Levels in Sepsis
Sepsis, Septic Shock
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.
Flavia Machado study chair
Federal University of São Paulo
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Aspirin in people with Sepsis, run by Federal University of São Paulo at 1 site in Brazil.
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 9 inclusion and 17 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: stopped early, as of the sponsor's last update on 13 Jul 2023. 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 Brazil. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Terminated: The study was stopped prematurely and will not be resumed due to the higher number of bleeding cases in the intervention group, as recomended by the Data Safety Monitoring Board on February 7, 2023.). Results are not available in the source record.
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?
Difference between the Sequential Organ Failure Assessment (SOFA) Score on the seventh day of ICU stay and baseline (DeltaSOFA D7-D1). (time frame: 7 days). 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 NCT01784159, which also lists 1 linked publication.
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 13 Jul 2023.