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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Stroke; G6PD Deficiency
• Intervention / Treatment: Drug: Aspirin; Drug: Clopidogrel

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.

• Study Type: Interventional
• Enrollment (Anticipated): 440
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jinsheng Zeng, MD,PhD; Phone Number: 13322800657; Email: zengjs@pub.guangzhou.gd.cn

Study Locations

• China
  • Fujian
    • Longyan, Fujian, China
      • Recruiting
      • Longyan First Hospital
      • Contact: Yangui Chen
    • Sanming, Fujian, China
      • Recruiting
      • Sanming First Hospital
      • Contact: Weimin Hong
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Recruiting
      • The First Affiliated Hospital of Sun Yat-sen University
    • Guangzhou, Guangdong, China, 510080
      • Recruiting
      • The First Affiliated Hospital of Guangdong Pharmaceutical University
    • Guangzhou, Guangdong, China, 510632
      • Not yet recruiting
      • The First Affiliated Hospital of Jinan University
    • Jieyang, Guangdong, China, 522000
      • Recruiting
      • Jieyang Municipal People's Hospital
      • Contact: Jiakai Li
    • Meizhou, Guangdong, China, 514000
      • Recruiting
      • Meizhou City People's Hospital
    • Shaoguan, Guangdong, China, 512026
      • Not yet recruiting
      • Yue Bei People's Hospital
    • Yunfu, Guangdong, China, 527300
      • Not yet recruiting
      • Yunfu People's Hospital
  • Guangxi
    • Baise, Guangxi, China, 533000
      • Recruiting
      • People's Hospital of Baise
      • Contact: Dengrong Ban
    • Liuzhou, Guangxi, China, 545005
      • Recruiting
      • The Forth Affiliated Hospital of Guangxi Medical Hospital
    • Nanning, Guangxi, China, 530021
      • Recruiting
      • The First Affiliated Hospital of Guangxi Medical Hospital
    • Yulin, Guangxi, China, 537400
      • Recruiting
      • Beiliu People's Hospital
      • Contact: Bin Chen
  • Hainan
    • Haikou, Hainan, China, 570311
      • Not yet recruiting
      • The Second Affiliated Hospital of Hainan Medical University
  • Jiangxi
    • Fengcheng, Jiangxi, China
      • Recruiting
      • Fengcheng People's Hospital
      • Contact: Hongxing Huang
    • Ganzhou, Jiangxi, China, 341000
      • Not yet recruiting
      • Ganzhou Municipal Hospital
    • Ganzhou, Jiangxi, China
      • Recruiting
      • First Affiliated hospital of GANNAN Medical University
      • Contact: Zheng Liu
    • Ganzhou, Jiangxi, China
      • Recruiting
      • Ganzhou People' Hospital
      • Contact: Xianghong Liu
    • Nanchang, Jiangxi, China, 330003
      • Not yet recruiting
      • The Forth Affiliated Hospital of Nanchang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aspirin; Drugs:Aspirin	Drug: Aspirin; This group will receive a 100 mg/day aspirin plus clopidogrel placebo for 90 days.; Other Names: Acetylsalicylic acid
Active Comparator: Clopidogrel; Drugs:Clopidogrel	Drug: Clopidogrel; This group will receive a 75 mg/day clopidogrel plus aspirin placebo for 90 days.; Other Names: Plavix

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in hemoglobin.		4 days,10±3 days,27±3 days and 90±5 days.
Change in reticulocyte.		4 days,10±3 days,27±3 days and 90±5 days.
Change in unconjugated bilirubin and total bilirubin.		4 days,10±3 days,27±3 days and 90±5 days.
Change in lactic dehydrogenase.		4 days,10±3 days,27±3 days and 90±5 days.
Proportion of major bleed (GUSTO definition).		90±5 days.
Overall mortality.		90±5 days.
Proportion of new clinical vascular events, defined as the composite of stroke, transient ischemic attack (TIA), myocardial infarction and vascular death.		90±5 days.
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.
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.
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.
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.

Collaborators and Investigators

• Sponsor: First Affiliated Hospital, Sun Yat-Sen University
• Investigators: Principal Investigator: Jinsheng Zeng, MD,PhD, First Affiliated Hospital, Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2020
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: September 8, 2019
• First Submitted That Met QC Criteria: September 11, 2019
• First Posted (Actual): September 12, 2019

Study Record Updates

• Last Update Posted (Actual): March 16, 2022
• Last Update Submitted That Met QC Criteria: March 15, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Aspirin; Clopidogrel; Acute ischemic stroke; Hemolysis; G6PD Deficiency; Anti-platelet therapy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Stroke; Glucosephosphate Dehydrogenase Deficiency; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Aspirin; Clopidogrel
• Other Study ID Numbers: SAST; 2018001 (Sun Yat-Sen University)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No