Ignite Creation Date:
2025-12-24 @ 11:10 PM
Ignite Modification Date:
2025-12-31 @ 6:49 PM
Study NCT ID:
NCT07121569
Status:
COMPLETED
Last Update Posted:
2025-08-17
First Post:
2025-08-06
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Oral DLBS1033 as Adjunctive Therapy in Acute Ischemic Stroke: Impact on Inflammatory Biomarkers and Outcomes
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000083242', 'term': 'Ischemic Stroke'}], 'ancestors': [{'id': 'D020521', 'term': 'Stroke'}, {'id': 'D002561', 'term': 'Cerebrovascular Disorders'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D014652', 'term': 'Vascular Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR'], 'maskingDescription': 'The study utilized a two-block randomization method to achieve balanced group assignments. Random allocation sequences were prepared by independent personnel and secured in sealed envelope. Each treatment package was labeled with a subject identification number corresponding to the generated random sequence and was distributed to eligible participants. The codes were kept confidential until the study was completed'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': "This randomized, double-masked controlled trial employed a rigorous experimental design to compare the adjunctive therapeutic effects of oral lumbrokinase DLBS1033 (490 mg, DISOLF film-coated tablet, Dexa Medica, 2 tab t.i.d.) versus placebo in patients with acute ischemic stroke over a 28-day prospective observation period. The study was conducted in the inpatient ward, with follow-up at the outpatient clinic of the Neurology Department, Dr. Moewardi General Hospital, Surakarta, Central Java, Indonesia, from July 2024 to March 2025, after obtaining full ethical clearance from the hospital's Health Research Ethics Committee"}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 52}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2024-07-06', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-08', 'completionDateStruct': {'date': '2025-03-13', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-08-12', 'studyFirstSubmitDate': '2025-08-06', 'studyFirstSubmitQcDate': '2025-08-06', 'lastUpdatePostDateStruct': {'date': '2025-08-17', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2025-08-13', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-03-04', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'MMP-9', 'timeFrame': 'Baseline, day 14 and 28', 'description': 'The inflammatory biomarkers were measured on the day of admission for stroke onset of 4-7 days, or on the third day for stroke onset of 1-3 days, and after the patient had received therapy on days 14 and 28'}, {'measure': 'IL-6', 'timeFrame': 'Baseline, day 14 and 28', 'description': 'The inflammatory biomarkers were measured on the day of admission for stroke onset of 4-7 days, or on the third day for stroke onset of 1-3 days, and after the patient had received therapy on days 14 and 28'}, {'measure': 'TNF-alpha', 'timeFrame': 'Baseline, day 14 and 28', 'description': 'The inflammatory biomarkers were measured on the day of admission for stroke onset of 4-7 days, or on the third day for stroke onset of 1-3 days, and after the patient had received therapy on days 14 and 28'}, {'measure': 'd-dimer', 'timeFrame': 'Baseline, day 14 and 28', 'description': 'The inflammatory biomarkers were measured on the day of admission for stroke onset of 4-7 days, or on the third day for stroke onset of 1-3 days, and after the patient had received therapy on days 14 and 28'}], 'secondaryOutcomes': [{'measure': 'TCD parameter-CIMT', 'timeFrame': 'Baseline, day 14 and 28', 'description': 'Measurement of carotid intima-media thickness using TCD examination of the CCA was performed on the day of admission for stroke onset of 4-7 days, or on the third day for stroke onset of 1-3 days, and after the patient had received therapy on days 14 and 28. CIMT values fall within a positive range, greater than 0, where higher values indicate a possible thickening of the blood vessels, as a sign of atherosclerosis'}, {'measure': 'TCD parameter-PI', 'timeFrame': 'Baseline, day 14 and 28', 'description': 'Measurement of the pulsatility index using TCD examination of the CCA, ICA, vertebral artery, MCA, ACA, PCA, and ROA was conducted on the day of admission for stroke onset of 4-7 days, or on the third day for stroke onset of 1-3 days, and after the patient had received therapy on days 14 and 28. PI values fall within a positive range, greater than 0, where higher values indicate greater vascular resistance.'}, {'measure': 'NIHSS', 'timeFrame': 'Baseline, day 14 and 28', 'description': 'Assessment of stroke severity was conducted by evaluating various neurological functions, including consciousness, gaze, visual field, facial palsy, extrimity function, ataxia, sensory, language, dysarthria, and aphasia. This assessment was performed before the patient received therapy and after the patient had undergone therapy for 14 and 28 days. Minimum score is 0 and maximum score is 42, where a higher NIHSS score indicates a more severe degree of stroke.'}, {'measure': 'Barthel Index', 'timeFrame': 'Baseline, day 14 and 28', 'description': 'Assessment of the ability to perform activities of daily living, such as eating, drinking, self-care, mobility, using the toilet, moving around, climbing stairs, dressing, and bladder and bowel control, was conducted before the patient received therapy and after the patient had undergone therapy for 14 and 28 days. Minimum score is 0 and maximum score is 100, where a higher Barthel Index score indicates better patient ADL function.'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Interleukin-6', 'Ischemic Stroke', 'Treatment outcome', 'Tumor Necrosis Factor-alpha', 'Oral lumbrokinase DLBS1033'], 'conditions': ['Ischemic Stroke, Acute']}, 'referencesModule': {'references': [{'pmid': '33927846', 'type': 'BACKGROUND', 'citation': 'Pinzon RT, Tjandrawinata RR, Wijaya VO, Veronica V. Effect of DLBS1033 on Functional Outcomes for Patients with Acute Ischemic Stroke: A Randomized Controlled Trial. Stroke Res Treat. 2021 Apr 7;2021:5541616. doi: 10.1155/2021/5541616. eCollection 2021.'}, {'pmid': '37627791', 'type': 'BACKGROUND', 'citation': 'Wang WL, Hsu YM, Lin ML, Chen SS, Lai YH, Huang CH, Yao CH. Ex Vivo Model to Evaluate the Antibacterial and Anti-Inflammatory Effects of Gelatin-Tricalcium Phosphate Composite Incorporated with Emodin and Lumbrokinase for Bone Regeneration. Bioengineering (Basel). 2023 Jul 31;10(8):906. doi: 10.3390/bioengineering10080906.'}], 'seeAlsoLinks': [{'url': 'https://perpustakaan.rsmoewardi.com/index.php?p=show_detail&id=1645&keywords=Dlbs1033', 'label': 'Related Info'}]}, 'descriptionModule': {'briefSummary': "This randomized, double-blind, placebo-controlled trial aims to evaluate the effect of oral DLBS1033 as adjunctive therapy on inflammatory biomarkers (IL-6, TNF-α, MMP-9, D-dimer), transcranial Doppler (TCD) parameters, and clinical outcomes in patients with acute ischemic stroke. Fifty-two eligible patients admitted to RSUD Dr. Moewardi Surakarta will be randomly assigned to receive either DLBS1033 (490 mg, DISOLF film-coated tablet, Dexa Medica, 2 tab t.i.d.) or placebo for 28 days, in addition to standard therapy between July 2024 to March 2025. The study was conducted in the inpatient ward, with follow-up at the outpatient clinic of the Neurology Department, Dr. Moewardi General Hospital, Surakarta, Central Java, following full ethical approval from the hospital's Health Research Ethics Committee. Primary outcomes include changes in inflammatory markers; secondary outcomes include changes in NIHSS and Barthel Index scores and TCD profiles.", 'detailedDescription': 'Intravenous thrombolysis with tissue plasminogen activator (tPA) or mechanical thrombectomy is considered first-line treatment to mediate reperfusion. Despite the rapid restoration of cerebral blood flow post-stroke, recanalization of occluded vessels can lead to progressive tissue damage, a condition known as ischemia-reperfusion injury. Reperfusion triggers a strong inflammatory response, supporting the development of a thrombo-inflammatory cascade. Previous studies have shown that lumbrokinase, a component of DLBS1033, plays a role in modulating the inflammatory cascade. Lumbrokinase has been shown to significantly reduce several inflammatory biomarkers, such as IL-6, TNF-alpha, and MMP-9, in an animal study level. However, no studies have yet examined the role of lumbrokinase in reducing TNF-α, MMP-9, and IL-6 levels in the blood of patients with ischemic stroke. Previous studies stated that administration of DLBS1033 significantly improves clinical outcomes in ischemic stroke patients, as measured by NIHSS and Barthel Index scores. Based on this background, the researcher is interested in investigating the effect of oral DLBS1033 as adjunctive therapy on the thrombo-inflammatory patho-mechanism in patients with ischemic stroke, as assessed by inflammatory biomarkers, TCD parameters, and clinical outcomes.\n\nEligible patients diagnosed with acute ischemic stroke, presenting within a time window of 24 hours to 7 days from symptom onset, will be enrolled and randomly assigned into two parallel groups in a 1:1 ratio. The diagnosis of ischemic stroke was made based on physical examination and confirmed by a non-contrast head CT scan performed by a neurologist. One group will receive oral DLBS1033 (490 mg, DISOLF film-coated tablet, Dexa Medica, 2 tab t.i.d.), while the other will receive a matching placebo. Both interventions will be administered alongside standard stroke treatment protocols for a duration of 28 days. Randomization will be stratified to ensure balanced baseline characteristics between groups. Random allocation sequences were prepared by independent team and secured in sealed envelope. Each treatment package was pre-labeled with a unique subject identification number that corresponded to the assigned number in the randomization sequence. Upon enrollment, eligible participants received the treatment package that matched their assigned number.\n\nThroughout the study, several key parameters will be assessed to evaluate the efficacy and safety of DLBS1033 as an adjunctive therapy. These include inflammatory biomarkers, such as serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), matrix metalloproteinase-9 (MMP-9), and D-dimer, which will be measured using validated immunoassay methods. In addition, cerebral hemodynamic status will be evaluated through Transcranial Doppler (TCD) ultrasonography to assess Pulsatility Index (PI), and carotid intima-media thickness (CIMT) will be measured via B-mode ultrasonography to examine vascular structural changes.\n\nTo evaluate clinical outcomes, the National Institutes of Health Stroke Scale (NIHSS) will be used to assess neurological deficits, and the Barthel Index will be used to evaluate functional independence in daily activities. All assessments, including laboratory biomarker tests, TCD and CIMT measurements, and clinical outcome scoring, will be conducted at three key time points: baseline, day 14, and day 28 post-initiation of therapy.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '19 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Inpatient with acute ischemic stroke onset 24 hours-7 days confirmed by CT scan.\n* First-ever or recurrent ischemic stroke.\n* Compos mentis on admission.\n* NIHSS score 5-25 on admission.\n* Willing to participate and signed informed consent\n\nExclusion Criteria:\n\n* Hemorrhagic stroke within the last 3 months.\n* Transient ischemic attack.\n* Pregnant, breastfeeding, or planning pregnancy.\n* Use of anticoagulants in the past month.\n* Nasogastric tube feeding.\n* Having or History of bleeding disorders or coagulopathy.\n* History of autoimmune disease.\n* Severe renal impairment (serum creatinine ≥3× normal or on hemodialysis).\n* Acute infection (systemic inflammatory response syndrome).\n* Hypersensitivity to DLBS1033'}, 'identificationModule': {'nctId': 'NCT07121569', 'briefTitle': 'Oral DLBS1033 as Adjunctive Therapy in Acute Ischemic Stroke: Impact on Inflammatory Biomarkers and Outcomes', 'organization': {'class': 'OTHER', 'fullName': 'Universitas Sebelas Maret'}, 'officialTitle': 'Efficacy of Oral DLBS1033 as Adjunctive Therapy in Acute Ischemic Stroke: A Randomized Controlled Trial Evaluating Inflammatory Biomarkers, TCD Results, and Clinical Outcomes', 'orgStudyIdInfo': {'id': 'DLBS1033 on Ischemic Stroke'}, 'secondaryIdInfos': [{'id': 'UST-003.24/DLBS1033/1/2024', 'type': 'OTHER', 'domain': 'Grantor or Funder: Dexa Medica Group'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Oral lumbrokinase DLBS1033 group', 'description': 'Patients with acute ischemic stroke who received oral lumbrokinase DLBS1033 (490 mg, DISOLF film-coated tablet, Dexa Medica, 2 tabs t.i.d.) and 100 mg acetylsalicylic acid as standard stroke therapy during 28-days observation period', 'interventionNames': ['Drug: Oral lumbrokinase DLBS1033']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Placebo group', 'description': 'Patients with acute ischemic stroke who received placebo (Placebo by Dexa Medica, 2 tabs t.i.d.) and 100 mg acetylsalicylic acid as standard stroke therapy during 28-days observation period', 'interventionNames': ['Drug: Placebo']}], 'interventions': [{'name': 'Oral lumbrokinase DLBS1033', 'type': 'DRUG', 'otherNames': ['DISOLF'], 'description': 'DLBS1033: 490 mg, DISOLF film-coated tablet, Dexa Medica, 2 tabs t.i.d', 'armGroupLabels': ['Oral lumbrokinase DLBS1033 group']}, {'name': 'Placebo', 'type': 'DRUG', 'description': 'Placebo by Dexa Medica, 2 tabs t.i.d.', 'armGroupLabels': ['Placebo group']}]}, 'contactsLocationsModule': {'locations': [{'zip': '57126', 'city': 'Surakarta', 'state': 'Central Java', 'country': 'Indonesia', 'facility': 'Dr. Moewardi Regional General Hospital', 'geoPoint': {'lat': -7.55611, 'lon': 110.83167}}], 'overallOfficials': [{'name': 'Firstiafina Tiffany, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Department of Neurology, Faculty of Medicine, Universitas Sebelas Maret'}]}, 'ipdSharingStatementModule': {'infoTypes': ['STUDY_PROTOCOL', 'SAP', 'CSR'], 'timeFrame': 'August 6th, 2025-August 6th, 2026', 'ipdSharing': 'YES', 'description': 'Publication in ICMJE journals', 'accessCriteria': 'Open access, every journal visitor'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Universitas Sebelas Maret', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Medical Doctor (Neurologist)', 'investigatorFullName': 'Firstiafina Tiffany', 'investigatorAffiliation': 'Universitas Sebelas Maret'}}}}