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

Sponsor

First Affiliated Hospital, Sun Yat-Sen University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04088513

Collaborator

(none)

440

Enrollment

Locations

Arms

59.3

Anticipated Duration (Months)

23.2

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
G6PD Deficiency Stroke	Drug: Aspirin Drug: Clopidogrel	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

440 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jan 22, 2020

Anticipated Primary Completion Date :

Dec 31, 2024

Anticipated Study Completion Date :

Dec 31, 2024

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Proportion of protocol-defined hemolysis. [90±5 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, adjudicated by the adjudication committee ultimately.

Secondary Outcome Measures

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. [90±5 days.]
Modified Rankin Scale score ranges from 0 to 6, and lower score means more functional independence.
Proportion of functional independence defined as Barthel Index 95-100. [90±5 days.]
Barthel Index ranges from 0 to 100, and higher score means more functional independence.
Change in National Institutes of Health Stroke Scale [90±5 days.]
National Institutes of Health Stroke Scale ranges from 0 to 42, and higher scores indicate more severe neurologic deficits.
Health related quality of life, assessed by EuroQoL-5 Dimensions questionnaire [90±5 days.]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age≥40 years(no upper limit)
Acute ischemic stroke within 14 days of symptoms onset;
Glucose-6-phosphate dehydrogenase deficiency screened in G6PD enzyme activity
Had not received aspirin 7 days prior to randomization
Informed consent signed

Exclusion Criteria:

Diagnosis of hemorrhage or other pathology, such as vascular malformation, tumor, abscess or other non-ischemic brain disease, base on head CT or MRI
Concomitant infections at the time of randomization
mRS>2 prior to the presenting stroke
Hemoglobin<10 g/dL prior to randomization
Received intravenous thrombolytic therapy or neurointervention treatment before randomization
Clear indication for anticoagulation (presumed cardioembolism, eg, atrial fibrillation, prosthetic cardiac valves or suspected endocarditis)
Clear indication for dual antiplatelet therapy (eg, minor stroke in 24h (NIHSS ≤3) or endovascular therapy for the indexed event)
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.
Anticipated concomitant therapy with long-term (>7 days) NSAIDs affecting platelet function
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)
Any history of thalassemia, autoimmune hemolytic disease, aplastic anemia or other severe hematologic diseases
Anticipated concomitant therapy with other contraindicated drugs for G6PD deficiency
Severe dysphagia to unable swallow the drugs
Concomitant infections and need for antimicrobial therapy
Intracranial hemorrhage or gastrointestinal bleed within 3 months, or major surgery within 30 days
Stomach tumor or any other malignant tumor
Planed surgery or interventional treatment that may affect the study procedure
Severe non-cardiovascular comorbidity with life expectancy <3 m
Female who is pregnant or lactating
Currently receiving an investigational drug or device
Inability to understand and/or comply with study procedures due to psychosis, cognition impairment or emotion disturbance.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Longyan First Hospital	Longyan	Fujian	China
2	Sanming First Hospital	Sanming	Fujian	China
3	The First Affiliated Hospital of Guangdong Pharmaceutical University	Guangzhou	Guangdong	China	510080
4	The First Affiliated Hospital of Sun Yat-Sen University	Guangzhou	Guangdong	China	510080
5	The First Affiliated Hospital of Jinan University	Guangzhou	Guangdong	China	510632
6	Jieyang Municipal People's Hospital	Jieyang	Guangdong	China	522000
7	Meizhou City People's Hospital	Meizhou	Guangdong	China	514000
8	Yue Bei People's Hospital	Shaoguan	Guangdong	China	512026
9	Yunfu People's Hospital	Yunfu	Guangdong	China	527300
10	People's Hospital of Baise	Baise	Guangxi	China	533000
11	The Forth Affiliated Hospital of Guangxi Medical Hospital	Liuzhou	Guangxi	China	545005
12	The First Affiliated Hospital of Guangxi Medical Hospital	Nanning	Guangxi	China	530021
13	Beiliu People's Hospital	Yulin	Guangxi	China	537400
14	The Second Affiliated Hospital of Hainan Medical University	Haikou	Hainan	China	570311
15	Fengcheng People's Hospital	Fengcheng	Jiangxi	China
16	Ganzhou Municipal Hospital	Ganzhou	Jiangxi	China	341000
17	First Affiliated Hospital of Gannan Medical University	Ganzhou	Jiangxi	China
18	Ganzhou People' Hospital	Ganzhou	Jiangxi	China
19	The Forth Affiliated Hospital of Nanchang University	Nanchang	Jiangxi	China	330003