Safety and Efficacy of Aspirin in Stroke Patients With Glucose-6-phosphate Dehydrogenase Deficiency (SAST)

Stroke Clinical Trial

— SAST  

Official title:

A Randomized, Double-blind, Active-Controlled Trial Comparing the Safety and Efficacy of Aspirin Versus Clopidogrel in Stroke Patients With Glucose-6-phosphate Dehydrogenase Deficiency

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04088513
• Other study ID #: SAST
• Secondary ID: 2018001
• Status: Recruiting
• Phase: Phase 4
• Start date: January 22, 2020
• Est. completion date: December 31, 2024

Study information

• Verified date: March 2022
• Source: First Affiliated Hospital, Sun Yat-Sen University
• Contact: Jinsheng Zeng, MD,PhD
• Phone: 13322800657
• Email: zengjs[@]pub.guangzhou.gd.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Aspirin was reported to induce hemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency on some occasions, while still widely uesd for stroke prevention. The SAST trial is designed to evaluate the safety and efficacy of aspirin in patients this enzyme disorder.The primary purpose of the trial is to evaluate the hemolytic effects of a 3-month regimen of aspirin 100mg/d versus a 3-month regimen of clopidogrel 75mg/d.

Description:

This SAST trial is a prospective, multicenter, randomized, double-blind trial.440 acute ischemic stroke (AIS) patients with G6PD deficiency will be randomized to receive a 3-month regimen of aspirin 100mg/d or clopidogrel 75mg/d. The primary end point is the proportion of protocol-defined hemolysis at 90 days. Protocol-defined hemolysis is defined as one or more of the following conditions: a) Hemoglobin level declined ≥2.5 g/dL from baseline, meanwhile ruling out bleeding events. b) Hemoglobin level declined ≥25% from baseline, meanwhile ruling out bleeding events. c) Clinically relevant hemolytic events, could manifested as fatigue, back pain, anemia, dark urine and jaundice. The study consists of five visits including the day of randomization, day 4, day10±3days, day27±3days, day90±7days.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 440
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

1. Age=40 years(no upper limit)

2. Acute ischemic stroke within 14 days of symptoms onset;

3. Glucose-6-phosphate dehydrogenase deficiency screened in G6PD enzyme activity

4. Had not received aspirin 7 days prior to randomization

5. Informed consent signed

Exclusion Criteria:

1. Diagnosis of hemorrhage or other pathology, such as vascular malformation, tumor, abscess or other non-ischemic brain disease, base on head CT or MRI

2. Concomitant infections at the time of randomization

3. mRS>2 prior to the presenting stroke

4. Hemoglobin<10 g/dL prior to randomization

5. Received intravenous thrombolytic therapy or neurointervention treatment before randomization

6. Clear indication for anticoagulation (presumed cardioembolism, eg, atrial fibrillation, prosthetic cardiac valves or suspected endocarditis)

7. Clear indication for dual antiplatelet therapy (eg, minor stroke in 24h (NIHSS =3) or endovascular therapy for the indexed event)

8. Anticipated concomitant antiplatelets other than aspirin or clopidogrel (eg, GPIIb/IIIa inhibitors, ticlopidine, prasugrel, dipyridamole, ozagrel, cilostazol, ticagrelor) and other antithrombotic agents with antiplatelet effects, including traditional/herbal medicine agents.

9. Anticipated concomitant therapy with long-term (>7 days) NSAIDs affecting platelet function

10. Contraindication to clopidogrel or aspirin (1)Known allergic reactions (2)Severe hepatic or renal dysfunction (Severe hepatic dysfunction is defined as serum ALT or AST >2 times the upper limit of the normal group;Severe renal dysfunction is defined as serum creatinine > 1.5 times the upper limit of the normal group) (3)Severe cardiac failure(NYHA class ? or ?) (4)Asthma (5)Any history of Hemostatic disorder or systemic bleeding (6)Any history of thrombocytopenia or neutropenia (7)Any history of drug-induced hematologic or hepatic insufficiency (8)Low white blood cell (<2×10^9/L) or platelet count (<100×10^9/L)

11. Any history of thalassemia, autoimmune hemolytic disease, aplastic anemia or other severe hematologic diseases

12. Anticipated concomitant therapy with other contraindicated drugs for G6PD deficiency

13. Severe dysphagia to unable swallow the drugs

14. Concomitant infections and need for antimicrobial therapy

15. Intracranial hemorrhage or gastrointestinal bleed within 3 months, or major surgery within 30 days

16. Stomach tumor or any other malignant tumor

17. Planed surgery or interventional treatment that may affect the study procedure

18. Severe non-cardiovascular comorbidity with life expectancy <3 m

19. Female who is pregnant or lactating

20. Currently receiving an investigational drug or device

21. Inability to understand and/or comply with study procedures due to psychosis, cognition impairment or emotion disturbance.

Related Conditions & MeSH terms

• G6PD Deficiency
• Glucosephosphate Dehydrogenase Deficiency
• Stroke

Intervention

Drug:
• Aspirin
This group will receive a 100 mg/day aspirin plus clopidogrel placebo for 90 days.
• Clopidogrel
This group will receive a 75 mg/day clopidogrel plus aspirin placebo for 90 days.

Locations

Country	Name	City	State
China	People's Hospital of Baise	Baise	Guangxi
China	Fengcheng People's Hospital	Fengcheng	Jiangxi
China	First Affiliated Hospital of Gannan Medical University	Ganzhou	Jiangxi
China	Ganzhou Municipal Hospital	Ganzhou	Jiangxi
China	Ganzhou People' Hospital	Ganzhou	Jiangxi
China	The First Affiliated Hospital of Guangdong Pharmaceutical University	Guangzhou	Guangdong
China	The First Affiliated Hospital of Jinan University	Guangzhou	Guangdong
China	The First Affiliated Hospital of Sun Yat-Sen University	Guangzhou	Guangdong
China	The Second Affiliated Hospital of Hainan Medical University	Haikou	Hainan
China	Jieyang Municipal People's Hospital	Jieyang	Guangdong
China	The Forth Affiliated Hospital of Guangxi Medical Hospital	Liuzhou	Guangxi
China	Longyan First Hospital	Longyan	Fujian
China	Meizhou City People's Hospital	Meizhou	Guangdong
China	The Forth Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	The First Affiliated Hospital of Guangxi Medical Hospital	Nanning	Guangxi
China	Sanming First Hospital	Sanming	Fujian
China	Yue Bei People's Hospital	Shaoguan	Guangdong
China	Beiliu People's Hospital	Yulin	Guangxi
China	Yunfu People's Hospital	Yunfu	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
First Affiliated Hospital, Sun Yat-Sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of protocol-defined hemolysis.	Protocol-defined hemolysis is defined as one or more of the following conditions: a) Hemoglobin level declined =2.5 g/dL from baseline, meanwhile ruling out bleeding events. b) Hemoglobin level declined =25% from baseline, meanwhile ruling out bleeding events. c) Clinically relevant hemolytic events, could manifested as fatigue, back pain, anemia, dark urine and jaundice, adjudicated by the adjudication committee ultimately.	90±5 days.
Secondary	Change in hemoglobin.		4 days,10±3 days,27±3 days and 90±5 days.
Secondary	Change in reticulocyte.		4 days,10±3 days,27±3 days and 90±5 days.
Secondary	Change in unconjugated bilirubin and total bilirubin.		4 days,10±3 days,27±3 days and 90±5 days.
Secondary	Change in lactic dehydrogenase.		4 days,10±3 days,27±3 days and 90±5 days.
Secondary	Proportion of major bleed (GUSTO de?nition).		90±5 days.
Secondary	Overall mortality.		90±5 days.
Secondary	Proportion of new clinical vascular events, de?ned as the composite of stroke, transient ischemic attack (TIA), myocardial infarction and vascular death.		90±5 days.
Secondary	Proportion of functional independence defined as modified Rankin Scale score 0-2.	Modified Rankin Scale score ranges from 0 to 6, and lower score means more functional independence.	90±5 days.
Secondary	Proportion of functional independence defined as Barthel Index 95-100.	Barthel Index ranges from 0 to 100, and higher score means more functional independence.	90±5 days.
Secondary	Change in National Institutes of Health Stroke Scale	National Institutes of Health Stroke Scale ranges from 0 to 42, and higher scores indicate more severe neurologic deficits.	90±5 days.
Secondary	Health related quality of life, assessed by EuroQoL-5 Dimensions questionnaire	EuroQoL-5 Dimensions questionnaire contains utility index score and visual analogue scale. Utility index score ranges from 0 to 1, and visual analogue scale ranges from 0 to 100. Higher scores indicate more healthy quality of life.	90±5 days.