The Role of DLBS1033 in

Acute Ischemic Stroke

Dr. dr. Rizaldy Pinzon, MKes, SpS
RS Bethesda/ FK UKDW Yogyakarta
Presented in SUNSHINE 2021
Email: drpinzon17@[Link]
Curiculum vitae
• S1 : FK UGM
• S2 : FK UGM
• Spesialis FK UGM
• S3 : FK UGM
• Pengajar S2 UGM dan FK UKDW Yogyakarta
• Dokter spesialis saraf RS Bethesda Yogyakarta
Stroke in Indonesia
High unmet needs in stroke care
Residual risk of stroke patient
• Despite the clinical benefit achieved with life-style modifications,
blood pressure reduction, statins, angiotensin II-active agents, and
antiplatelet agents, the residual risk for recurrent acute events in
patients with atherothrombotic disease remains substantial.
• Observational registry data confirm the high residual risk of patients
and highlight the need for more effective therapies.
Residual risk of stroke patients
• Current antiplatelet agents target thromboxane A2 and adenosine
diphosphate and do not interfere with a multitude of other platelet
activation pathways that may contribute to thrombotic events.
• There is a critical need for novel therapies that provide more
comprehensive platelet inhibition when used with current oral
antiplatelet therapy for greater protection against thrombotic events,
preferably without an incremental bleeding risk.
Lumbricus rubellus extract action
• Fibrin inhibitors;
• Fibrinogen inhibitors;
• Fibrinolysis stimulants;
• Fibrinolytic agents;
• Janus kinase 1 inhibitors;
• Matrix metalloproteinase 9 inhibitors;
• NF-kappa B inhibitors;
• Platelet aggregation inhibitors;
• STAT1 transcription factor inhibitors;
• Tumour necrosis factor alpha inhibitors
• DLBS1033 was found to possess fibrinogenolytic activity on α-, β-, and
γ-chain of fibrinogen.
• It also induced antiplatelet aggregation and prolonged blood clotting
time.
• Thrombolytic properties of DLBS1033 were shown with its fast and
long-acting fibrinolytic activity, as well as its effective blood clot lysis
activities.
• DLBS1033 conferred antithrombotic and thrombolytic action which
could be used as a safe and promising oral thrombolytic drug.
 Vol 9, Issue 1, 2016 ISSN - 0974-2441
Research Article

HEMOSTASIS PROFILE AND CLINICAL OUTCOME OF ACUTE ISCHEMIC STROKE PATIENTS

TREATED WITH ORAL LUMBROKINASE DLBS1033: A COMPARATIVE STUDY VERSUS ASPIRIN
AND CLOPIDOGREL

ISMAIL SETYOPRANOTO1, SAMEKTO WIBOWO1, RAYMOND R TJANDRAWINATA2*

1
Department of Neurology, Faculty of Medicine, University of Gadjah Mada/Dr. Sardjito Hospital, Yogyakarta, Indonesia. 2Dexa

• This was a 3-arm, parallel, randomized, controlled, open-label, blinded-

Laboratories of Biomolecular Sciences, Dexa Medica Group, Indonesia. Email: raymond@[Link]
Received: 20 August 2015, Revised and Accepted: 30 September 2015

evaluation study involving 126 acute ischemic stroke patients.

ABSTRACT

Objectives: This clinical study was conducted to determine the hemostasis profile and clinical outcome of acute ischemic stroke patients treated with

• Aspirin 80 mg daily (Group 1), or clopidogrel 75 mg daily (Group 2),

DLBS1033 in comparison with aspirin or clopidogrel. DLBS1033 is a proprietary bioactive protein fraction derived from the earthworms (Lumbricus
rubellus) that possesses both fibrinolytic and antithrombotic properties.

DLBS1033 490 mg 3 times daily (Group 3), for 90 days.

Methods: This was a 3-arm, parallel, randomized, controlled, open-label, blinded-evaluation study involving 126 acute ischemic stroke patients. Each
subject received any of the following study medication within 96 hrs after the stroke onset: Aspirin 80 mg daily (Group 1), or clopidogrel 75 mg daily

• Hemostasis parameters evaluated were prothrombin time (PT), activated

(Group 2), DLBS1033 490 mg 3 times daily (Group 3), for 90 days. Hemostasis parameters evaluated were prothrombin time (PT), activated partial
thromboplastin time (aPTT), and international normalized ratio (INR), while the clinical outcomes were measured using Gadjah Mada Stroke Scale
(SSGM) and Barthel index (BI).
partial thromboplastin time (aPTT), and international normalized ratio
Results: Baseline characteristics, including the hemostasis and clinical profiles, were comparable between groups. At the end of the study, PT, aPTT,

(INR), while the clinical outcomes were measured using Gadjah Mada
and INR values were not significantly different between groups, which were all within the normal ranges. There was a significant improvement of BI
as well as SSGM from baseline in each group. The improvement size of BI was found similar between groups (p=0.098). However, a significantly better

Stroke Scale (SSGM) and Barthel index (BI).

improvement of SSGM was observed in those received DLBS1033 (6.98±4.90; p=0.001 vs. aspirin [3.74±3.66], p=0.006 vs. clopidogrel [4.26±4.21]).

Conclusion: It was concluded that DLBS1033 provided a safe hemostasis profile (PT, aPTT, and INR) comparable to that of aspirin or clopidogrel in

• At the end of the study, PT, aPTT, and INR values were not significantly
ischemic stroke patients. Treatment with DLBS1033 improved clinical outcomes indicated by the BI and SSGM, and the improvement size of SSGM was
even better than that of aspirin or clopidogrel treatment.

different between groups

Keywords: Acute ischemic stroke, Barthel index, DLBS1033, Hemostasis, Gadjah Mada Stroke Scale, Oral lumbrokinase.

• There was a significant improvement of BI as well as SSGM from baseline in

INTRODUCTION possesses strong fibrinolytic and fibrinogenolytic properties, lowers

each group. The improvement size of BI was found similar between groups
Thrombosis remains involved in the pathological course of some most
blood viscosity, markedly inhibits platelet aggregation, and promotes
thrombus degradation without causing excessive bleeding [17-19].

(p=0.098).
common vascular diseases, including ischemic stroke [1,2]. Substantial
progress has been made in understanding the biology of thrombus
formation and the pathophysiology of thrombosis. Several more established
Lumbrokinase is stable over a wide range of pH and temperature; thus,
it can be administered orally [20].

pharmacologic agents, including thrombolytic therapy, antiplatelet agents, DLBS1033 investigated in this clinical study is a lumbrokinase
and anticoagulants, have been recommended for the early management fractionated from the earthworms, Lumbricus rubellus, through a
of acute ischemic stroke [3]. However, all the recommended, as well as proprietary technology of extraction. DLBS1033 possesses eight
neuro-protective agents available for prevention or treatment that have major proteins, each with a molecular weight below 100 kDa, named
 Vol 9, Issue 1, 2016 ISSN - 0974-2441
Research Article

HEMOSTASIS PROFILE AND CLINICAL OUTCOME OF ACUTE ISCHEMIC STROKE PATIENTS

TREATED WITH ORAL LUMBROKINASE DLBS1033: A COMPARATIVE STUDY VERSUS ASPIRIN
AND CLOPIDOGREL
Setyopranoto et al.
ISMAIL SETYOPRANOTO1, SAMEKTO WIBOWO1, RAYMOND R TJANDRAWINATA2* Asian J Pharm Clin Res, Vol 9, Issue 1, 2016, 186-192

1
Department of Neurology, Faculty of Medicine, University of Gadjah Mada/Dr. Sardjito Hospital, Yogyakarta, Indonesia. 2Dexa
Laboratories of Biomolecular Sciences, Dexa Medica Group, Indonesia. Email: raymond@[Link]
Received: 20 August 2015, Revised and Accepted: 30 September 2015

ABSTRACT

Objectives: This clinical study was conducted to determine the hemostasis profile and clinical outcome of acute ischemic stroke patients treated with
DLBS1033 in comparison with aspirin or clopidogrel. DLBS1033 is a proprietary bioactive protein fraction derived from the earthworms (Lumbricus
rubellus) that possesses both fibrinolytic and antithrombotic properties.

Methods: This was a 3-arm, parallel, randomized, controlled, open-label, blinded-evaluation study involving 126 acute ischemic stroke patients. Each
subject received any of the following study medication within 96 hrs after the stroke onset: Aspirin 80 mg daily (Group 1), or clopidogrel 75 mg daily
(Group 2), DLBS1033 490 mg 3 times daily (Group 3), for 90 days. Hemostasis parameters evaluated were prothrombin time (PT), activated partial
thromboplastin time (aPTT), and international normalized ratio (INR), while the clinical outcomes were measured using Gadjah Mada Stroke Scale
(SSGM) and Barthel index (BI).

Results: Baseline characteristics, including the hemostasis and clinical profiles, were comparable between groups. At the end of the study, PT, aPTT,
Fig. 1: Effect of aspirin, clopidogrel, and DLBS1033 treatment on the functional outcome measured by Barthel index. The error bars
and INR values were not significantly different between groups, which were all within the normal ranges. There was a significant improvement of BI
represent the standard errors; Wilcoxon signed-rank was used in within-group analysis; Kruskal–Wallis was used in between-group
as well as SSGM from baseline in each group. The improvement size of BI was found similar between groups (p=0.098). However, a significantly better
analysis
improvement of SSGM was observed in those received DLBS1033 (6.98±4.90; p=0.001 vs. aspirin [3.74±3.66], p=0.006 vs. clopidogrel [4.26±4.21]).

Conclusion: It was concluded that DLBS1033 provided a safe hemostasis profile (PT, aPTT, and INR) comparable to that of aspirin or clopidogrel in
ischemic stroke patients. Treatment with DLBS1033 improved clinical outcomes indicated by the BI and SSGM, and the improvement size of SSGM was
even better than that of aspirin or clopidogrel treatment.

Keywords: Acute ischemic stroke, Barthel index, DLBS1033, Hemostasis, Gadjah Mada Stroke Scale, Oral lumbrokinase.

INTRODUCTION possesses strong fibrinolytic and fibrinogenolytic properties, lowers

blood viscosity, markedly inhibits platelet aggregation, and promotes
Thrombosis remains involved in the pathological course of some most
thrombus degradation without causing excessive bleeding [17-19].
common vascular diseases, including ischemic stroke [1,2]. Substantial Lumbrokinase is stable over a wide range of pH and temperature; thus,
progress has been made in understanding the biology of thrombus it can be administered orally [20].
formation and the pathophysiology of thrombosis. Several more established
pharmacologic agents, including thrombolytic therapy, antiplatelet agents, DLBS1033 investigated in this clinical study is a lumbrokinase
and anticoagulants, have been recommended for the early management fractionated from the earthworms, Lumbricus rubellus, through a
of acute ischemic stroke [3]. However, all the recommended, as well as proprietary technology of extraction. DLBS1033 possesses eight
Fig. 2. Effect
neuro-protective agents available for prevention or treatment of aspirin, clopidogrel, and DLBS1033 treatment on the neurological outcome measured by Gadjah Mada Stroke Scale. The
that have major proteins, each with a molecular weight below 100 kDa, named
error
been in use for decades, have currently been replaced with barsvariants
newer represent the standard errors; Wilcoxon signed-rank was used in within-group analysis; Kruskal–Wallis was used in between-
as Lumbricus low-molecular-weight proteins [21]. This specific
that offer a modest incremental improvement [4-10]. Yet, the ideal drug group analysis
pattern of proteins confers a unique characteristic of DLBS1033
studies for the past 1 month, and (iii) Not competent
Ethical approval number 07/KEPK-RSB/I/20 was obtained
Improvement in Functional Status of Acute Ischemic Stroke
enough in giving approval and answering questionnaires.
from Bethesda Hospital, Yogyakarta, Indonesia. This
Patients Treated with DLBS1033
research as
hasAdd
Subjects were withdrawn from this study if: (i) subjects been on Therapy
registered at Center for Health
experienced any serious adverse events, (ii) subjects were
Resources and Services Research and Development
: A Randomized Controlled
suffering from any disease that would interfere with
Indonesia withStudythe ethical approval number of
medication and evaluation, (iii) subjects died. 1087/C.16/FK/2019.
1
R. T. Pinzon , V. Veronica2*
1
Lecturer, department of neurology, faculty of medicine, Duta Wacana Christian University, Wahidin Sudirohusodo st.
5-25, Yogyakarta 55224, Indonesia
2
Research assistant, department of neurology, faculty of medicine, Duta Wacana Christian University, Wahidin
Sudirohusodo st. 5-25, Yogyakarta 55224, Indonesia

Abstract
Background: DLBS0133 – a lumbrokinase fractionated from the earthworms, Lumbricus rubellus – was a promising agent
in patients with ischemic stroke.
Aims: Measure the benefit of DLBS1033 as add on therapy for ischemic stroke patients.
Methods: This was randomized, controlled, open-label study from the period of November 2019 - April 2020 at Bethesda
Hospital, Yogyakarta, Indonesia. The subjects were randomized into 2 groups: control group who received standard therapy
or experimental group who received standard therapy and DLBS1033 3 times daily. Disabilities were measured with
modified Rankin Scale (mRS), National Institutes of Health Stroke Scale (NIHSS) score, and Barthel Index (BI) between 2
groups. The analysis is intention to treat based.
Results: The data were obtained from 60 ischemic stroke patients, consist of 36 male and 24 female. The mean age was
61.9±12.462 years old. There were significant improvements in mRS (3.30±0.724 vs 1.78±0.974) (p <0.001), NIHSS
(7.11±2.806 vs 2±2.787) (p <0.001) and BI (4.63±3.53 vs 14.52±5.199) (p <0.001) scores after treatment in experimental
group. The improvements of mRS (3.11±0.801 vs 2.26±1.059) (p <0.001), NIHSS (6.19±2.788 vs 2.52±3.227) (p <0.001),
and BI (6.59±4.693 vs 13.44± 5.905) (p <0.001) in control group were also significant. Differences of mRS (1.52±0.643 vs
0.85±0.534) (p <0,001), NIHSS (5.11±1.826 vs 3.67±1.941) (p: 0,012), and BI (9.96±3.716 vs 6.85±3.146) (p: 0,001) scores
between 2 groups were significantly different.
Conclusion: DLBS1033 has proven to improve functional outcomes better than standard therapy. This study did not find
any adverse events related to DLBS1033.
Keywords: DLBS1033, Standard therapy, lumbrokinase, Acute ischemic stroke, Functional outcomes.

INTRODUCTION MATERIAL AND METHODS

The second spot as the leading cause of death and the third Study Design
spot as the leading cause of disability-adjusted life years This was randomized, controlled, open-label, study from
(DALYs) lost in 2017 were claimed by stroke [1]. Stroke the period of November 2019 - April 2020 at Bethesda
is more common in developing countries than developed Hospital, Yogyakarta, Indonesia. Yogyakarta has the
countries [2]. Stroke's mortality and DALYs lost in second highest stroke cases among provinces in Indonesia
Indonesia consecutively are Figure 1: The flow
119.5/100,000 and diagram
[10]. of the research
2,857.91/100,000 - the highest among any other country in There were 60 acute ischemic stroke patients who fulfilled
South-East Asia [1]. the inclusion and exclusion criteria. Each subject recruited
OutcomesStroke
Measurement between 2 groups. Chi-square
can be divided into 2 main types, which are from acute stroke intensive care unit
test
[Link] to compares
Pinzon al /J. the
et up
followed
mRS Sci.
Pharm. & Res. Vol. 12(5), 2020, 667-672
Disabilities on onset and hospital discharge were evaluated and BI scores at hospital discharge
ischemic stroke and hemorrhagic stroke. Ischemic stroke from the first day they were hospitalized until hospitalbetween 2 groups, and
with modified
occursRankin Scalesupplies
when blood (mRS),toNational
brain areInstitutes
obstructed,of discharge
also compares adverse events.
(died or discharged Statistical
alive). Eligible significance was
subjects
Improvement of BI scores in experimental group
Before therapy Improvement in Functional 4.63 Status of Acute Ischemic Stroke
(3.65)
Patients Treated with DLBS1033 as Add on Therapy <0.001
After therapy 14.52 (5.199)
Improvement of BI scores in control : A Randomized
group Controlled Study
1 2
Before therapy R. T. Pinzon
6.59, V. Veronica
(4.693) *
1
Lecturer, department of neurology, faculty of medicine, Duta Wacana Christian University, Wahidin Sudirohusodo st. <0.001
5-25, Yogyakarta 55224, Indonesia
After therapy 2 13.44 (5.905)
Research assistant, department of neurology, faculty of medicine, Duta Wacana Christian University, Wahidin
Sudirohusodo st. 5-25, Yogyakarta 55224, Indonesia

Table 3. Comparison
Abstract of differences in mRS, NIHSS, and BI scores between experimental and control group
Background: DLBS0133 – a lumbrokinase fractionated from the earthworms, Lumbricus rubellus – was a promising agent
in patients with ischemic stroke. Mean (s.d)
Aims: Measure the benefit of DLBS1033 as add on therapy for ischemic stroke patients.
p
Comparison of the difference
Hospital, Yogyakarta, mRSThe
in Indonesia. scores between
subjects were randomized into22 groups
Methods: This was randomized, controlled, open-label study from the period of November 2019 - April 2020 at Bethesda
groups: control group who received standard therapy
or experimental group who received standard therapy and DLBS1033 3 times daily. Disabilities were measured with
Difference of mRS scores modifiedinRankin Scale (mRS), Nationalgroup
experimental 1.52score,
Institutes of Health Stroke Scale (NIHSS) (0.643)
and Barthel Index (BI) between 2
groups. The analysis is intention to treat based. <0.001
Difference of mRS scores Results:inThecontrol group
data were obtained from 60 ischemic stroke patients, consist0.85 (0.534)
of 36 male and 24 female. The mean age was
61.9±12.462 years old. There were significant improvements in mRS (3.30±0.724 vs 1.78±0.974) (p <0.001), NIHSS
Comparison of the difference in NIHSS scores between 2 groups
(7.11±2.806 vs 2±2.787) (p <0.001) and BI (4.63±3.53 vs 14.52±5.199) (p <0.001) scores after treatment in experimental
group. The improvements of mRS (3.11±0.801 vs 2.26±1.059) (p <0.001), NIHSS (6.19±2.788 vs 2.52±3.227) (p <0.001),
and BI (6.59±4.693 vs 13.44± 5.905) (p <0.001) in control group were also significant. Differences of mRS (1.52±0.643 vs
Difference of NIHSS scores0.85±0.534)in(p <0,001), NIHSS (5.11±1.826group
experimental vs 3.67±1.941) (p: 0,012), and BI5.11 (1.826)
(9.96±3.716 vs 6.85±3.146) (p: 0,001) scores
between 2 groups were significantly different. 0.012
Difference of NIHSS scoresConclusion:in control
DLBS1033 group
has proven
any adverse events related to DLBS1033.
3.67
to improve functional outcomes better than (1.941)
standard therapy. This study did not find

Comparison of the difference in BI scores between 2 groups

Keywords: DLBS1033, Standard therapy, lumbrokinase, Acute ischemic stroke, Functional outcomes.

Difference of BI scores INTRODUCTION group

in experimental 9.96 A(3.716)
MATERIAL ND METHODS
The second spot as the leading cause of death and the third Study Design 0.001
spot as the in
Difference of BI scores leading cause of group
control disability-adjusted life years This was randomized, 6.85 (3.146)
controlled,
(DALYs) lost in 2017 were claimed by stroke [1]. Stroke the period of November 2019 - April 2020 at Bethesda
open-label, study from

is more common in developing countries than developed Hospital, Yogyakarta, Indonesia. Yogyakarta has the
countries [2]. Stroke's mortality and DALYs lost in second highest stroke cases among provinces in Indonesia
Table 4. Comparison of mRS and BI scores between experimental and control group at hospital discharge
Indonesia consecutively are 119.5/100,000 and [10].
2,857.91/100,000 - the highest among any other country in There were 60 acute ischemic stroke patients who fulfilled
South-East Asia [1]. mRS scores the inclusion and exclusion criteria. Each subject recruited
Stroke can be divided into 2 main types, which are /J. Pharm. Sci. & Res. Vol. 12(5), p2020, 667-672
[Link]
from acute stroke intensive care unit Pinzon et up
followed al
<2 (good outcomes) ≥2 (poor outcomes)
ischemic stroke and hemorrhagic stroke. Ischemic stroke
occurs when blood supplies to brain are obstructed,
from the first day they were hospitalized until hospital
discharge (died or discharged alive). Eligible subjects
 Enrollment Assessed for eligibility (n= 180)

Excluded (n= 0)
¨ Not meeting inclusion criteria (n= 0)
¨ Declined to participate (n= 0)
¨ Other reasons (n= 0)

Randomized (n= 180)

Allocation
Experimental group (n= 90) Control group (n= 90)
¨ Received DLBS1033 + Standard therapy ¨ Received standard therapy (n= 90)
(n= 90)

Follow-Up
Experimental group (n= 72) Experimental group (n= 69)
¨ Lost to follow-up (n= 10) ¨ Lost to follow-up (n= 8)

¨ Adverse events (n= 8) ¨ Adverse events (n= 11)

¨ Died (n= 0) ¨ Died (n= 2)

Analysis
Analysed (n= 90) Analysed (n= 90)
Table 1. Subjects' Clinical Characteristics
No. (%)
Experimental Control Total p
Characteristic group (n=90) group (n=90) (n=180) value
Age, mean (SD), y 61.4 (10.0) 61.3 (11.8) 62.4 (11.0) 0.24
Gender
Male 54 (60%) 54 (60%) 108 (60%) 1
Female 36 (40%) 36 (40%) 72 (40%)
Marriage
Married 76 (84.4%) 73 (81.1%) 149 (82.8%)
Divorced 11 (12.2%) 15 (16.7%) 26 (14.4%) 0.645
Not married 3 (3.3%) 2 (2.2%) 5 (2.8%)
Education
Elementary school 18 (20%) 14 (15.6%) 32 (17.8%)
Junior high school 13 (14.4%) 12 (13.3%) 25 (13.9%)
Senior high school 25 (27.8%) 30 (33.3%) 55 (30.6%) 0.901
Bachelor degree 21 (23.3%) 20 (22.2%) 41 (22.8%)
Others 13 (14.4%) 14 (15.6%) 27 (15%)
Occupation
Civil servant 7 (7.8%) 4 (4.4%) 11 (6.1%)
Entrepreneur 14 (15.6%) 6 (6.7%) 20 (11.1%)
Private employee 10 (11.1%) 10 (11.1%) 20 (11.1%)
0.138
Retired 18 (20%) 28 (31.1%) 46 (25.6%)
Unemployment 14 (15.6%) 21 (23.3%) 35 (19.4%)
Others 27 (30%) 21 (23.3%) 48 (26.7%)
Type of Health Financing
Public insurance 64 (71.1%) 64 (71.1%) 128 (71.1%)
Private insurance 1 (1.1%) 0 (0%) 1 (0.6%)
0.498
Fee for service 23 (25.6%) 21 (23.3%) 44 (24.4%)
Company insurance 2 (2.2%) 5 (5.6%) 7 (3.9%)
Comorbidities
Hypertension 49 (54.4%) 47 (52.2%) 96 (53.3%) 0.765
Diabetes mellitus 30 (33.3%) 30 (33.3%) 60 (33.3%) 1
Cardiovascular disease 19 (21.1%) 20 (22.2%) 39 (21.7%) 0.856
Gastrointestinal disease 3 (3.3%) 8 (8.9%) 11 (6.1%) 0.12
Others 4 (4.4%) 7 (7.8%) 11 (6.1%) 0.351
Concomitant medications
Antihypertensive medication 45 (50%) 45 (50%) 90 (50%) 1
Antidiabetic medication 29 (32.2%) 30 (33.3%) 59 (32.8%) 0.874
Antiplatelet 84 (93.3%) 86 (95.6%) 170 (94.4%) 0.515
PPI/ H2 blocker 2 (2.2%) 1 (1.1%) 3 (1.7%) 1
Anticoagulant 0 (0%) 0 (0%) 0 (0%) 1
Figure 2. Change from baseline in mean average National Institutes of Health Stroke Scale
(NIHSS) score during treatment period and follow-up period.

Figure 3. Change from baseline in mean average Barthel Index (BI) score during treatment period
and follow-up period.
Figure 4 . Modifed Rankin Scale score distribution at baseline onset, discharge, and at day 30 of
stroke in experimental group (DLBS1033 therapy + standard treatment)

Figure 5. Modifed Rankin Scale score distribution at baseline onset, discharge, and at day 30 of
stroke in control group (standard treatment only)
 Table 5. Adverse events
No. (%)
Experimental group Control group Total (n=180) p value
(n=90) (n=90)
Hospital discharge
Any adverse 6 (6.7%) 8 (8.9%) 14 (7.8%) 0.548
event
No adverse 83 (92.2%) 79 (87.8%) 162 (90%)
event
Day 30
Any adverse 2 (2.2%) 3 (3.3%) 5 (5.6%) 0.605
event
No adverse 74 (82.2%) 69 (76.7%) 143 (79.4%)
event

Table 6. Type of adverse events

This trial showed that DLBS1033 No. was (%) more effective in
Type of adverse Experimental group Control group (n=90) Total (n=180)
improving
event functional(n=90)
status compared to standard care only
GI discomfort 2 (2.2%) 3 (3.3%) 5 (2.8%)
in acute
Heartburn ischemic stroke patients
1 (1.1%) with a
5 (5.6%) similar 6safety
(3.3%) profile.
OurVomiting
study may
GI tract bleeding support1 (1.1%)
the
4 (4.4%) use of 0 (0%)
DLBSS1033
3 (3.3%)
1 (0.6%)
as an adjuvant
7 (3.9%)
treatment
Cephalalgia
for
Thrombocytopenia
patients with
1 (1.1%)
1 (1.1%)
acute ischemic
0 (0%)
1 (1.1%)
stroke.
1 (0.6%)
2 (1.1%)
Anemia 0 (0%) 1 (1.1%) 1 (0.6%)
Abbreviations: GI, gastrointestinal.
• Except for rtPA, few of these
agents have succeeded in
clinical trials.
• Recently, with the
understanding of the
pathophysiological process of
stroke, there is a resurrection
of research on
developing neuroprotective
agents for stroke treatment,
and novel molecular targets
for neuroprotection and
neurorestoration have been
discovered to predict or offer
clinical benefits.
• MMP-9 released from
neutrophils allows these cells to
transmigrate into the brain
tissue, where they release
MMP-9 and other deleterious
agents such as ROS.
• Neutrophil-derived MMP-9
actively degrades components
of the BBB leading to the
development of cerebral edema
and hemorrhagic transformation.
Conclusion
• Stroke is major cause of death and disability worldwide
• There is an unmet need of stroke care
• The recurrence is high
• The DLBS 1033 has anti thrombotic and fibrinolytic action, and
multiple mechanism for preventing inflammation and apoptosis
• Previous studies and ours showed the promising result