Clinical trial NCT04088513: Safety and Efficacy of Aspirin in Stroke Patients With Glucose-6-phosphate Dehydrogenase Deficiency (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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: G6PD Deficiency
Stroke
Keywords: G6PD Deficiency
Acute ischemic stroke
Aspirin
Hemolysis
Clopidogrel
Anti-platelet therapy
Lead sponsor: First Affiliated Hospital, Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2019-09-12
Enrollment: 440
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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 Ⅲ or Ⅳ) (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.

Primary outcomes:
measure: Proportion of protocol-defined hemolysis.
timeFrame: 90±5 days.
Secondary outcomes:
measure: Change in hemoglobin.
timeFrame: 4 days,10±3 days,27±3 days and 90±5 days.
measure: Change in reticulocyte.
timeFrame: 4 days,10±3 days,27±3 days and 90±5 days.
measure: Change in unconjugated bilirubin and total bilirubin.
timeFrame: 4 days,10±3 days,27±3 days and 90±5 days.
measure: Change in lactic dehydrogenase.
timeFrame: 4 days,10±3 days,27±3 days and 90±5 days.
measure: Proportion of major bleed (GUSTO deﬁnition).
timeFrame: 90±5 days.
measure: Overall mortality.
timeFrame: 90±5 days.
measure: Proportion of new clinical vascular events, deﬁned as the composite of stroke, transient ischemic attack (TIA), myocardial infarction and vascular death.
timeFrame: 90±5 days.
measure: Proportion of functional independence defined as modified Rankin Scale score 0-2.
timeFrame: 90±5 days.
measure: Proportion of functional independence defined as Barthel Index 95-100.
timeFrame: 90±5 days.
measure: Change in National Institutes of Health Stroke Scale
timeFrame: 90±5 days.
measure: Health related quality of life, assessed by EuroQoL-5 Dimensions questionnaire
timeFrame: 90±5 days.
Other outcomes:
Locations:
city: Longyan
country: China
facility: Longyan First Hospital
state: Fujian
city: Sanming
country: China
facility: Sanming First Hospital
state: Fujian
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangdong Pharmaceutical University
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Sun Yat-Sen University
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Jinan University
state: Guangdong
city: Jieyang
country: China
facility: Jieyang Municipal People's Hospital
state: Guangdong
city: Meizhou
country: China
facility: Meizhou City People's Hospital
state: Guangdong
city: Shaoguan
country: China
facility: Yue Bei People's Hospital
state: Guangdong
city: Yunfu
country: China
facility: Yunfu People's Hospital
state: Guangdong
city: Baise
country: China
facility: People's Hospital of Baise
state: Guangxi
city: Liuzhou
country: China
facility: The Forth Affiliated Hospital of Guangxi Medical Hospital
state: Guangxi
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical Hospital
state: Guangxi
city: Yulin
country: China
facility: Beiliu People's Hospital
state: Guangxi
city: Haikou
country: China
facility: The Second Affiliated Hospital of Hainan Medical University
state: Hainan
city: Fengcheng
country: China
facility: Fengcheng People's Hospital
state: Jiangxi
city: Ganzhou
country: China
facility: Ganzhou Municipal Hospital
state: Jiangxi
city: Ganzhou
country: China
facility: First Affiliated Hospital of Gannan Medical University
state: Jiangxi
city: Ganzhou
country: China
facility: Ganzhou People' Hospital
state: Jiangxi
city: Nanchang
country: China
facility: The Forth Affiliated Hospital of Nanchang University
state: Jiangxi
Study officials:
affiliation: First Affiliated Hospital, Sun Yat-Sen University
name: Jinsheng Zeng, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: