ASpirin for Patients With SEPsis and SeptIc Shock (ASP-SEPSIS)

July 12, 2023 updated by: Flavia Ribeiro Machado, Federal University of São Paulo

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.

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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:

  1. Signature of informed consent
  2. Patients must be older than 18 years old

  3. 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:

  1. Pregnancy
  2. Impossibility to use the intestinal tract
  3. Death perspective in less than 24 hours
  4. Patients in the end of their lives or in exclusive palliative care
  5. Patients with active bleeding
  6. Prior study participation
  7. Known allergy to aspirin
  8. Active peptic ulcer
  9. Previous use of antiplatelet agents in the last 7 days
  10. Previous use of AINEs in the last 7 days, except for dipyrone.
  11. Hemorrhagic stroke in the last 7 days or central nervous system surgery in the last 72 hours.
  12. Platelets <30,000 cells/mm3.
  13. 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.
  14. Ophthalmologic surgery postoperative and transurethral resection of the prostate at the discretion of the attending physician.
  15. Hepatic cirrhosis or previous liver disease with altered prothrombin activity, manifested by INR above 2.0 or other previous coagulopathies.
  16. Severe head injury in the last 7 days.
  17. 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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
167

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Brazil
      • São Paulo, Brazil, 04024002
        • Hospital Sao Paulo

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Eligibility - patients:

Inclusion criteria:

The three criteria below must be present:

  1. Signature of informed consent
  2. Patients must be older than 18 years old

  3. 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
    • 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

Exclusion Criteria:

  1. Pregnancy
  2. Impossibility to use the intestinal tract
  3. Death perspective in less than 24 hours
  4. Patients in the end of their lives or in exclusive palliative care
  5. Patients with active bleeding
  6. Prior study participation
  7. Known allergy to aspirin
  8. Active peptic ulcer
  9. Previous use of antiplatelet agents in the last 7 days
  10. Previous use of AINEs in the last 7 days, except for dipyrone.
  11. Hemorrhagic stroke in the last 7 days or central nervous system surgery in the last 72 hours.
  12. Platelets <30,000 cells/mm3.
  13. 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.
  14. Ophthalmologic surgery postoperative and transurethral resection of the prostate at the discretion of the attending physician.
  15. Hepatic cirrhosis or previous liver disease with altered prothrombin activity, manifested by INR above 2.0 or other previous coagulopathies.
  16. Severe head injury in the last 7 days.
  17. Use or indication of anticoagulation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo
Placebo 1tb / day/ 7days
Drug: Aspirin
Aspirin administration for 7 days
Other Names:
  • AAS
Active Comparator: Aspirin
Intervention aspirin 200 mg/day for 7 days
Drug: Aspirin
Aspirin administration for 7 days
Other Names:
  • AAS

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
7 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Mechanical ventilation free days;
Time Frame: 28 days
To evaluate if the aspirin use reduces the time of mechanical ventilation, that ranges between 0 and 28 days.
28 days
Vasopressor free days
Time Frame: 28 days
To evaluate if the aspirin use reduces the days using vasoressors, that ranges between 0 and 28 days.
28 days
Intensive Care Unit (ICU) free days
Time Frame: 28 days
Length of stay in the ICU, that ranges between 0 and 28 days
28 days
Hospital free days
Time Frame: 28 days
Length of stay in the hospital, that ranges between 0 and 28 days
28 days
Renal replacement therapy
Time Frame: 28 days
Length of stay in renal replacement therapy, that ranges between 0 and 28 days
28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Federal University of São Paulo

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Flavia Machado, Federal University of São Paulo

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 27, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 15, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 5, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 1, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 4, 2013

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 5, 2013

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 13, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 12, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • EPM81449

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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