ASP-SEPSIS: ASpirin for Patients With SEPsis and SeptIc Shock

Sponsor
Federal University of São Paulo (Other)
Overall Status
Recruiting
CT.gov ID
NCT01784159
Collaborator
(none)
218
1
2
57.2
3.8

Study Details

Study Description

Brief 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 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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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 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

Study Type:
Interventional
Anticipated Enrollment :
218 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
placebo
Primary Purpose:
Treatment
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.
Actual Study Start Date :
Mar 27, 2019
Anticipated Primary Completion Date :
Nov 30, 2023
Anticipated Study Completion Date :
Dec 31, 2023

Arms and Interventions

Arm Intervention/Treatment
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
  • Outcome Measures

    Primary Outcome Measures

    1. Difference between the Sequential Organ Failure Assessment (SOFA) Score on the seventh day of ICU stay and baseline (DeltaSOFA D7-D1). [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.

    Secondary Outcome Measures

    1. Mechanical ventilation free days; [28 days]

      To evaluate if the aspirin use reduces the time of mechanical ventilation, that ranges between 0 and 28 days.

    2. Vasopressor free days [28 days]

      To evaluate if the aspirin use reduces the days using vasoressors, that ranges between 0 and 28 days.

    3. Intensive Care Unit (ICU) free days [28 days]

      Length of stay in the ICU, that ranges between 0 and 28 days

    4. Hospital free days [28 days]

      Length of stay in the hospital, that ranges between 0 and 28 days

    5. Renal replacement therapy [28 days]

      Length of stay in renal replacement therapy, that ranges between 0 and 28 days

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Hospital São Paulo São Paulo Brazil 04024002

    Sponsors and Collaborators

    • Federal University of São Paulo

    Investigators

    • Study Chair: Flavia Machado, Federal University of São Paulo

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Flavia Ribeiro Machado, Professor of Intensive Care Medicine, Federal University of São Paulo
    ClinicalTrials.gov Identifier:
    NCT01784159
    Other Study ID Numbers:
    • EPM81449
    First Posted:
    Feb 5, 2013
    Last Update Posted:
    Apr 13, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Flavia Ribeiro Machado, Professor of Intensive Care Medicine, Federal University of São Paulo
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Apr 13, 2022