Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT01784159 |
| Other study ID # |
EPM81449 |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
March 27, 2019 |
| Est. completion date |
January 5, 2023 |
Study information
| Verified date |
July 2023 |
| Source |
Federal University of São Paulo |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical 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 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.
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.
