<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01694537</url>
  </required_header>
  <id_info>
    <org_study_id>DLBS1033</org_study_id>
    <nct_id>NCT01694537</nct_id>
  </id_info>
  <brief_title>The Effects of DLBS1033 on Haemostasis Parameters in Healthy Volunteers</brief_title>
  <official_title>The Effects of DLBS1033 on Haemostasis Parameters in Healthy Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Indonesia University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Dexa Medica Group</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Indonesia University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      DLBS1033 is bioactive protein fraction which extracted from Lumbricus rubellus earthworm.&#xD;
      This earthworm comes from Pengalengan, West Java, Indonesia. DLBS1033 possesses 8 major&#xD;
      proteins with molecular weight below 100 kDa, so its named as Lumbricus Low Molecular weight&#xD;
      Proteins (LLP). This enzym can be transported to the bloodstream via intestinal epitel.&#xD;
      Structure of DLBS1033 looks like lumbrokinase. Lumbrokinase is enzym that consist of 6&#xD;
      isoenzyme serine protease. As a drug that consists of serin protease enzym, suspected that&#xD;
      the mechanism of action of DLBS1033 similar with lumbrokinase, especially as plasminogen&#xD;
      activator in fibrinolytic system. In vitro study by Trisina et al showed that DLBS1033 has&#xD;
      fibrinogenolytic activities on fibrinogen α, beta, and gamma chain, decreasing platelet&#xD;
      aggregation and clotting time was prolonged. Until now, the mechanism of action and effects&#xD;
      of DLBS1033 on human fibrinolytic and coagulation system still unknown. Therefore, the aim of&#xD;
      this clinical trial is to evaluate the effects of DLBS1033 on human fibrinolytic and&#xD;
      coagulation system on healthy subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Fibrinolysis is a process to lyse clot formed by thrombin. It starts with activating&#xD;
      plasminogen to plasmin by the endogenous tissue plasminogen activator (tPA) and urokinase&#xD;
      plasminogen activator (uPA). These activator are found in the endothelium, granulocytes and&#xD;
      monocytes. Plasminogen activator inhibitor-1 (PAI-1) is the major inhibitor of tPA and uPA)&#xD;
      and α2-antiplasmin is major inhibitor of plasmin. Plasmin wil degrade soluble fibrinogen and&#xD;
      fibrin to produce fibrinogen degradation products and fibrin degradation products,&#xD;
      respectively.&#xD;
&#xD;
      Lumbrokinase has been investigated in animal studies. Kim et al was conducting on rats by&#xD;
      administered freeze-dried powder of Lumbricus rubellus earthworm orally. This study showed&#xD;
      that earthworm powder is valuable for the prevention and/or treatment of thrombotic&#xD;
      conditions. Similar conclusion also shown on study by Lee et al, which compared&#xD;
      antithrombotic and fibrinolytic activities of lumbrokinase SPP-501 (extracted from Eisenia&#xD;
      andrei earthworm) with urokinase and t-PA in a thrombosis model of rat vena. The results of&#xD;
      this study were decreasing of thrombus weight, shortening of euglobulin lysis time (ELT), and&#xD;
      reducing platelet aggregation of rat which given SPP-501.&#xD;
&#xD;
      Conclusion from several clinical trial similar with several studies on animal. From study&#xD;
      which was conducted by Jin et al on 51 cerebral infarct subjects which were given 3 times 400&#xD;
      mg lumbrokinase (n = 31) or control (n = 20) for 28 days. In the treatment group, kaolin&#xD;
      partial thromboplastin time (KPTT) was prolonged, t-PA activity and D-dimer level increase,&#xD;
      and fibrinogen decreased significantly. It is concluded that mechanism of lumbrokinase as&#xD;
      oral antithrombotic and fibrinolytic are by inhibition of coagulation intrinsic pathway and&#xD;
      activate fibrinolytic pathway by increasing t-PA activity. Fibrinolytic activity was also&#xD;
      concluded by Rey, who was conducted study on 28 diabetic foot ulcer subjects, which were&#xD;
      given 3 times 500 mg lumbrokinase per day (n = 14) for 7 days, or placebo. On this study, in&#xD;
      the treatment group mean of D-dimer was increased.&#xD;
&#xD;
      From many clinical trials, it is concluded that effects of lumbrokinase have seen after&#xD;
      several days. It is different with intravenous fibrinolytic enzym, such as streptokinase and&#xD;
      t-PA, which effects have seen soon after it was used. Therefore oral lumbrokinase could not&#xD;
      replace the function of intravenous fibrinolytic enzym,that was used on acute thrombosis.&#xD;
      Based on antithrombotic and fibrinolytic activity, lumbrokinase might used as secondary&#xD;
      prevention after acute thrombosis, such as myocard infarct and stroke. Some researchers have&#xD;
      started clinical trials about that hypothesis.&#xD;
&#xD;
      Pilot study by Kasim et al was used a lumbrokinase in 10 patient with stable angina pectoris.&#xD;
      This study showed that 70% of total sample receiving lumbrokinase had a significant decrease&#xD;
      in summed stress score of perfusion imaging and better perfusion in viable myocardium after&#xD;
      30 days of lumbrokinase treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 2012</start_date>
  <completion_date type="Actual">December 2012</completion_date>
  <primary_completion_date type="Actual">October 2012</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>plasmin-antiplasmin complex (PAP complex)</measure>
    <time_frame>one week</time_frame>
    <description>changes in plasmin-antiplasmin complex</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>euglobulin clot lysis time (ECLT)</measure>
    <time_frame>one week</time_frame>
    <description>changes in euglobulin clot lysis time</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>prothrombin time (PT)</measure>
    <time_frame>one week</time_frame>
    <description>changes in prothrombin time</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>fibrinogen</measure>
    <time_frame>one week</time_frame>
    <description>changes in fibrinogen</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>activated partial thromboplastin time (aPTT)</measure>
    <time_frame>one week</time_frame>
    <description>changes in activated partial thromboplastin time</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>platelet aggregation</measure>
    <time_frame>one week</time_frame>
    <description>changes in platelet aggregation</description>
  </secondary_outcome>
  <other_outcome>
    <measure>serum creatinine</measure>
    <time_frame>one week</time_frame>
    <description>serum creatinine</description>
  </other_outcome>
  <other_outcome>
    <measure>serum glutamic oxaloacetic transaminase (SGOT)</measure>
    <time_frame>one week</time_frame>
    <description>changes in serum glutamic oxaloacetic transaminase</description>
  </other_outcome>
  <other_outcome>
    <measure>serum glutamic pyruvic transaminase (SGPT)</measure>
    <time_frame>one week</time_frame>
    <description>changes in serum glutamic pyruvic transminase</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The comparison drug is placebo, which is made with same size and shape with study drug. DLBS1033 and placebo is produced by PT Dexa Medica. Placebo will taken 3 times 1 tablet per day for 7 days. Wash out period before enter another arm is 7 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>DLBS1033</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The study drug is enteric coated DLBS1033, which contain 490 mg bioactive protein fraction. The drug will taken 3 times 490 mg per day for 7 days. Wash out period before enter another arm is 7 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DLBS1033</intervention_name>
    <description>The study drug is enteric coated DLBS1033, which contain 490 mg bioactive protein fraction.</description>
    <arm_group_label>DLBS1033</arm_group_label>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>Placebo is made with same size and shape with study drug.</description>
    <arm_group_label>DLBS1033</arm_group_label>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male&#xD;
&#xD;
          -  18-55 years old&#xD;
&#xD;
          -  body mass index between 18-25 kg/square metres&#xD;
&#xD;
          -  normal physical examination&#xD;
&#xD;
          -  Patient still have the ability to undergo examinations and give written informed&#xD;
             consent&#xD;
&#xD;
          -  Plasmin-antiplasmin complex (PAP complex) level between 0-514 ng/ml&#xD;
&#xD;
          -  Platelet aggregation (ADP 10 uM) &gt; 49%&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient with cardiovascular disease, hypertension, diabetes mellitus, and dyslipidemia&#xD;
&#xD;
          -  Creatinin serum more than 1,5 x upper limit normal&#xD;
&#xD;
          -  SGOT and SGPT more than 3 x upper limit normal&#xD;
&#xD;
          -  Blood pressure ≥ 140/90 mmHg&#xD;
&#xD;
          -  Fasting blood glucose &gt; 126 mg/dL&#xD;
&#xD;
          -  Alcohol patients&#xD;
&#xD;
          -  Took any medications (including traditional medicine, supplement and vitamin) in 1&#xD;
             week before the study)&#xD;
&#xD;
          -  Patient has bleeding history which unclear etiology&#xD;
&#xD;
          -  Hemoglobin &lt; 10 g/dL&#xD;
&#xD;
          -  Thrombocyte count &lt; 100.000/uL&#xD;
&#xD;
          -  Heavy smoker (Bringman Index &gt; 600)&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nafrialdi, MD, PhD, SpPD, SpFK</last_name>
    <role>Principal Investigator</role>
    <affiliation>Indonesia University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Indonesia University</name>
      <address>
        <city>Jakarta</city>
        <zip>10430</zip>
        <country>Indonesia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Indonesia</country>
  </location_countries>
  <reference>
    <citation>Mihara H, Sumi H, Yoneta T, Mizumoto H, Ikeda R, Seiki M, Maruyama M. A novel fibrinolytic enzyme extracted from the earthworm, Lumbricus rubellus. Jpn J Physiol. 1991;41(3):461-72. doi: 10.2170/jjphysiol.41.461.</citation>
    <PMID>1960890</PMID>
  </reference>
  <reference>
    <citation>Kasim M, Kiat AA, Rohman MS, Hanifah Y, Kiat H. Improved myocardial perfusion in stable angina pectoris by oral lumbrokinase: a pilot study. J Altern Complement Med. 2009 May;15(5):539-44. doi: 10.1089/acm.2008.0506.</citation>
    <PMID>19416019</PMID>
  </reference>
  <reference>
    <citation>Yan XM, Kim CH, Lee CK, Shin JS, Cho IH, Sohn UD. Intestinal Absorption of Fibrinolytic and Proteolytic Lumbrokinase Extracted from Earthworm, Eisenia andrei. Korean J Physiol Pharmacol. 2010 Apr;14(2):71-5. doi: 10.4196/kjpp.2010.14.2.71. Epub 2010 Apr 30.</citation>
    <PMID>20473377</PMID>
  </reference>
  <results_reference>
    <citation>Lee CK, Shin JS, Kim BS, Cho IH, Kim YS, Lee EB. Antithrombotic effects by oral administration of novel proteinase fraction from earthworm Eisenia andrei on venous thrombosis model in rats. Arch Pharm Res. 2007 Apr;30(4):475-80. doi: 10.1007/BF02980222.</citation>
    <PMID>17489364</PMID>
  </results_reference>
  <results_reference>
    <citation>Kim YS, Pyo MK, Park KM, Hahn BS, Yang KY, Yun-Choi HS. Dose dependency of earthworm powder on antithrombotic and fibrinolytic effects. Arch Pharm Res. 1998 Aug;21(4):374-7. doi: 10.1007/BF02974629.</citation>
    <PMID>9875462</PMID>
  </results_reference>
  <results_reference>
    <citation>Schmaier AH, Thornburg CD, Pipe SW. Coagulation and Fibrinolysis. In: McPherson RA, Pincus MR, editor. Henry's Clinical Diagnosis and Management by Laboratory Methods. 21st ed. Philadelphia: Saunders Elsevier; 2007. p. 731-3.</citation>
  </results_reference>
  <results_reference>
    <citation>Jin L, Jin H, Zhang G, Xu G. Changes in coagulation and tissue plasminogen activator after the treatment of cerebral infarction with lumbrokinase. Clin Hemorheol Microcirc. 2000;23(2-4):213-8.</citation>
    <PMID>11321442</PMID>
  </results_reference>
  <results_reference>
    <citation>Rey I. Pengaruh pemberian lumbrokinase selama 7 hari terhadap status hiperkoagulasi pada penderita ulkus kaki diabetik. Tugas Akhir Dalam Rangka menyelesaikan Pendidikan Dokter Spesialis Ilmu Penyakit Dalam. FK-USU, Medan. 2009.</citation>
  </results_reference>
  <results_reference>
    <citation>Trisina J, Sunardi F, Suhartono MT, Tjandrawinata RR. DLBS1033, a protein extract from Lumbricus rubellus, possesses antithrombotic and thrombolytic activities. J Biomed Biotechnol. 2011;2011:519652. doi: 10.1155/2011/519652. Epub 2011 Mar 3.</citation>
    <PMID>21403877</PMID>
  </results_reference>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>September 7, 2012</study_first_submitted>
  <study_first_submitted_qc>September 25, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 27, 2012</study_first_posted>
  <last_update_submitted>May 11, 2017</last_update_submitted>
  <last_update_submitted_qc>May 11, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 15, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Indonesia University</investigator_affiliation>
    <investigator_full_name>Nafrialdi</investigator_full_name>
    <investigator_title>MD, PhD, SpPD, SpFK</investigator_title>
  </responsible_party>
  <keyword>lumbrokinase</keyword>
  <keyword>fibrinolytic</keyword>
  <keyword>plasmin-antiplasmin complex</keyword>
  <keyword>euglobulin clot lysis time</keyword>
  <keyword>platelet aggregation</keyword>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01694537
org study id: DLBS1033
nct id: NCT01694537
lead sponsor: 
collaborator: 
has dmc: Yes
DLBS1033 is bioactive protein fraction which extracted from Lumbricus rubellus earthworm.
      This earthworm comes from Pengalengan, West Java, Indonesia. DLBS1033 possesses 8 major
      proteins with molecular weight below 100 kDa, so its named as Lumbricus Low Molecular weight
      Proteins (LLP). This enzym can be transported to the bloodstream via intestinal epitel.
      Structure of DLBS1033 looks like lumbrokinase. Lumbrokinase is enzym that consist of 6
      isoenzyme serine protease. As a drug that consists of serin protease enzym, suspected that
      the mechanism of action of DLBS1033 similar with lumbrokinase, especially as plasminogen
      activator in fibrinolytic system. In vitro study by Trisina et al showed that DLBS1033 has
      fibrinogenolytic activities on fibrinogen α, beta, and gamma chain, decreasing platelet
      aggregation and clotting time was prolonged. Until now, the mechanism of action and effects
      of DLBS1033 on human fibrinolytic and coagulation system still unknown. Therefore, the aim of
      this clinical trial is to evaluate the effects of DLBS1033 on human fibrinolytic and
      coagulation system on healthy subjects.
Fibrinolysis is a process to lyse clot formed by thrombin. It starts with activating
      plasminogen to plasmin by the endogenous tissue plasminogen activator (tPA) and urokinase
      plasminogen activator (uPA). These activator are found in the endothelium, granulocytes and
      monocytes. Plasminogen activator inhibitor-1 (PAI-1) is the major inhibitor of tPA and uPA)
      and α2-antiplasmin is major inhibitor of plasmin. Plasmin wil degrade soluble fibrinogen and
      fibrin to produce fibrinogen degradation products and fibrin degradation products,
      respectively.

      Lumbrokinase has been investigated in animal studies. Kim et al was conducting on rats by
      administered freeze-dried powder of Lumbricus rubellus earthworm orally. This study showed
      that earthworm powder is valuable for the prevention and/or treatment of thrombotic
      conditions. Similar conclusion also shown on study by Lee et al, which compared
      antithrombotic and fibrinolytic activities of lumbrokinase SPP-501 (extracted from Eisenia
      andrei earthworm) with urokinase and t-PA in a thrombosis model of rat vena. The results of
      this study were decreasing of thrombus weight, shortening of euglobulin lysis time (ELT), and
      reducing platelet aggregation of rat which given SPP-501.

      Conclusion from several clinical trial similar with several studies on animal. From study
      which was conducted by Jin et al on 51 cerebral infarct subjects which were given 3 times 400
      mg lumbrokinase (n = 31) or control (n = 20) for 28 days. In the treatment group, kaolin
      partial thromboplastin time (KPTT) was prolonged, t-PA activity and D-dimer level increase,
      and fibrinogen decreased significantly. It is concluded that mechanism of lumbrokinase as
      oral antithrombotic and fibrinolytic are by inhibition of coagulation intrinsic pathway and
      activate fibrinolytic pathway by increasing t-PA activity. Fibrinolytic activity was also
      concluded by Rey, who was conducted study on 28 diabetic foot ulcer subjects, which were
      given 3 times 500 mg lumbrokinase per day (n = 14) for 7 days, or placebo. On this study, in
      the treatment group mean of D-dimer was increased.

      From many clinical trials, it is concluded that effects of lumbrokinase have seen after
      several days. It is different with intravenous fibrinolytic enzym, such as streptokinase and
      t-PA, which effects have seen soon after it was used. Therefore oral lumbrokinase could not
      replace the function of intravenous fibrinolytic enzym,that was used on acute thrombosis.
      Based on antithrombotic and fibrinolytic activity, lumbrokinase might used as secondary
      prevention after acute thrombosis, such as myocard infarct and stroke. Some researchers have
      started clinical trials about that hypothesis.

      Pilot study by Kasim et al was used a lumbrokinase in 10 patient with stable angina pectoris.
      This study showed that 70% of total sample receiving lumbrokinase had a significant decrease
      in summed stress score of perfusion imaging and better perfusion in viable myocardium after
      30 days of lumbrokinase treatment.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: plasmin-antiplasmin complex (PAP complex)
time frame: one week
description: changes in plasmin-antiplasmin complex
measure: euglobulin clot lysis time (ECLT)
time frame: one week
description: changes in euglobulin clot lysis time
measure: prothrombin time (PT)
time frame: one week
description: changes in prothrombin time
measure: fibrinogen
time frame: one week
description: changes in fibrinogen
measure: activated partial thromboplastin time (aPTT)
time frame: one week
description: changes in activated partial thromboplastin time
measure: platelet aggregation
time frame: one week
description: changes in platelet aggregation
measure: serum creatinine
time frame: one week
description: serum creatinine
measure: serum glutamic oxaloacetic transaminase (SGOT)
time frame: one week
description: changes in serum glutamic oxaloacetic transaminase
measure: serum glutamic pyruvic transaminase (SGPT)
time frame: one week
description: changes in serum glutamic pyruvic transminase
arm group label: placebo
arm group type: Placebo Comparator
description: The comparison drug is placebo, which is made with same size and shape with study drug. DLBS1033 and placebo is produced by PT Dexa Medica. Placebo will taken 3 times 1 tablet per day for 7 days. Wash out period before enter another arm is 7 days.
arm group label: DLBS1033
arm group type: Experimental
description: The study drug is enteric coated DLBS1033, which contain 490 mg bioactive protein fraction. The drug will taken 3 times 490 mg per day for 7 days. Wash out period before enter another arm is 7 days.
intervention type: Drug
intervention name: DLBS1033
description: The study drug is enteric coated DLBS1033, which contain 490 mg bioactive protein fraction.
arm group label: DLBS1033
arm group label: placebo
intervention type: Drug
intervention name: placebo
description: Placebo is made with same size and shape with study drug.
arm group label: DLBS1033
arm group label: placebo
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Nafrialdi, MD, PhD, SpPD, SpFK
role: Principal Investigator
affiliation: Indonesia University
facility: 
country: Indonesia
citation: Mihara H, Sumi H, Yoneta T, Mizumoto H, Ikeda R, Seiki M, Maruyama M. A novel fibrinolytic enzyme extracted from the earthworm, Lumbricus rubellus. Jpn J Physiol. 1991;41(3):461-72. doi: 10.2170/jjphysiol.41.461.
PMID: 1960890
citation: Kasim M, Kiat AA, Rohman MS, Hanifah Y, Kiat H. Improved myocardial perfusion in stable angina pectoris by oral lumbrokinase: a pilot study. J Altern Complement Med. 2009 May;15(5):539-44. doi: 10.1089/acm.2008.0506.
PMID: 19416019
citation: Yan XM, Kim CH, Lee CK, Shin JS, Cho IH, Sohn UD. Intestinal Absorption of Fibrinolytic and Proteolytic Lumbrokinase Extracted from Earthworm, Eisenia andrei. Korean J Physiol Pharmacol. 2010 Apr;14(2):71-5. doi: 10.4196/kjpp.2010.14.2.71. Epub 2010 Apr 30.
PMID: 20473377
citation: Lee CK, Shin JS, Kim BS, Cho IH, Kim YS, Lee EB. Antithrombotic effects by oral administration of novel proteinase fraction from earthworm Eisenia andrei on venous thrombosis model in rats. Arch Pharm Res. 2007 Apr;30(4):475-80. doi: 10.1007/BF02980222.
PMID: 17489364
citation: Kim YS, Pyo MK, Park KM, Hahn BS, Yang KY, Yun-Choi HS. Dose dependency of earthworm powder on antithrombotic and fibrinolytic effects. Arch Pharm Res. 1998 Aug;21(4):374-7. doi: 10.1007/BF02974629.
PMID: 9875462
citation: Schmaier AH, Thornburg CD, Pipe SW. Coagulation and Fibrinolysis. In: McPherson RA, Pincus MR, editor. Henry's Clinical Diagnosis and Management by Laboratory Methods. 21st ed. Philadelphia: Saunders Elsevier; 2007. p. 731-3.
citation: Jin L, Jin H, Zhang G, Xu G. Changes in coagulation and tissue plasminogen activator after the treatment of cerebral infarction with lumbrokinase. Clin Hemorheol Microcirc. 2000;23(2-4):213-8.
PMID: 11321442
citation: Rey I. Pengaruh pemberian lumbrokinase selama 7 hari terhadap status hiperkoagulasi pada penderita ulkus kaki diabetik. Tugas Akhir Dalam Rangka menyelesaikan Pendidikan Dokter Spesialis Ilmu Penyakit Dalam. FK-USU, Medan. 2009.
citation: Trisina J, Sunardi F, Suhartono MT, Tjandrawinata RR. DLBS1033, a protein extract from Lumbricus rubellus, possesses antithrombotic and thrombolytic activities. J Biomed Biotechnol. 2011;2011:519652. doi: 10.1155/2011/519652. Epub 2011 Mar 3.
PMID: 21403877
responsible party type: Principal Investigator
investigator affiliation: Indonesia University
investigator full name: Nafrialdi
investigator title: MD, PhD, SpPD, SpFK
sharing ipd: No