Effects of Lumbrokinase DLBS1033 on D-Dimer, Interleukin-6, and Clinical Outcomes in Patients With Pneumonia and Sepsis

NCT07892794 | Completed Phase 2

• 2 other identifiers: UST-002.25/DLBS1033/1/202568.2/UN27/KS/2025
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Pneumonia is a lung infection that can cause serious complications, especially when accompanied by sepsis. Sepsis can trigger excessive inflammation and abnormal blood clotting, potentially leading to organ damage and delayed recovery. Two blood markers, D-dimer and interleukin-6 (IL-6), may increase in patients with these conditions. Lumbrokinase DLBS1033 (Disolf®) is an oral treatment derived from the earthworm Lumbricus rubellus. It has properties that may help break down fibrin, a protein involved in blood clot formation, and reduce inflammation. This study aimed to determine whether adding Lumbrokinase DLBS1033 to standard hospital treatment could improve D-dimer and IL-6 levels, shorten the time needed to achieve clinical stability, and reduce the length of hospital stay in patients with pneumonia, sepsis, and hypercoagulability. The study was conducted at Dr. Moewardi General Hospital in Surakarta, Indonesia. A total of 50 hospitalized patients were randomly assigned to two groups of 25 participants each. One group received standard treatment plus oral Lumbrokinase DLBS1033, while the other group received standard treatment plus a placebo containing no active study medicine. Neither the participants nor the blinded study investigators knew which treatment was assigned. Blood samples were collected at three assessment points: baseline (H0), day 10 (H10), and a clinical stability-related assessment designated H+1. D-dimer and IL-6 levels were measured to assess changes in blood clotting activity and inflammation. Participants were also monitored for clinical stability using Halm's Criteria, length of hospital stay, and potential adverse events. The study hypothesis was that Lumbrokinase DLBS1033, when added to standard treatment, would improve D-dimer and IL-6 levels and promote faster clinical recovery compared with standard treatment plus placebo.

Conditions

Pneumonia; Sepsis; Blood Coagulation Disorders

Keywords

Lumbrokinase DLBS1033; D-dimer; Interleukin-6 (IL-6); Time to Clinical Stability; Length of Stay; Randomized Controlled Trial; Hypercoagulability; Halm's Criteria

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in D-Dimer Level

  Changes in blood D-dimer concentration were evaluated to assess coagulation-related responses to Lumbrokinase DLBS1033. D-dimer levels were measured in ng/mL at baseline (H0), day 10 (H10), and the clinical stability-related assessment (H+1). Changes from baseline were calculated for each participant as the D-dimer concentration at H10 or H+1 minus the baseline concentration at H0. Negative values indicate a reduction in D-dimer levels. The magnitude of change was compared between the Lumbrokinase DLBS1033 and placebo groups.

  Baseline (Day 0), Day 10, and the clinical stability-related assessment (H+1) during hospitalization.

• Change From Baseline in Interleukin-6 (IL-6) Level

  Changes in blood interleukin-6 (IL-6) concentration were evaluated to assess the inflammatory response to Lumbrokinase DLBS1033. IL-6 levels were measured in pg/mL at baseline (H0), day 10 (H10), and the clinical stability-related assessment (H+1). Changes from baseline were calculated for each participant as the IL-6 concentration at H10 or H+1 minus the baseline concentration at H0. Negative values indicate a reduction in IL-6 levels. The magnitude of change was compared between the Lumbrokinase DLBS1033 and placebo groups.

  Baseline (Day 0), Day 10, and the clinical stability-related assessment (H+1) during hospitalization.

Secondary Outcomes (2)

• Time to Clinical Stability Based on Halm's Criteria

  From hospital admission until first achievement of clinical stability according to Halm's Criteria, assessed daily for up to 9 days.

• Length of Hospital Stay

  From hospital admission until discharge, assessed for up to 17 days.

Study Arms (2)

Standard Therapy + Placebo

PLACEBO COMPARATOR

Participants in the placebo comparator group received standard medical treatment for pneumonia complicated by sepsis and hypercoagulability, including appropriate antimicrobial and supportive therapies, together with matching oral placebo tablets. The placebo was administered as one tablet twice daily during hospitalization until clinical stability was achieved according to Halm's Criteria.

Drug: Placebo Tablet(s)

Standard Therapy + Lumbrokinase DLBS1033

EXPERIMENTAL

Participants in the experimental group received standard medical treatment for pneumonia complicated by sepsis and hypercoagulability, including appropriate antimicrobial and supportive therapies, together with oral Lumbrokinase DLBS1033 (Disolf® 490 mg). The study drug was administered as one tablet twice daily (total daily dose: 980 mg) during hospitalization until clinical stability was achieved according to Halm's Criteria.

Drug: DLBS1033

Interventions

Placebo Tablet(s) DRUG

Matching placebo tablets containing no active Lumbrokinase DLBS1033 were administered orally as one tablet twice daily, together with standard medical treatment for pneumonia complicated by sepsis and hypercoagulability. The placebo was administered according to the same treatment schedule as the experimental intervention until clinical stability was achieved based on Halm's Criteria.

Standard Therapy + Placebo

DLBS1033 DRUG

Lumbrokinase DLBS1033 (Disolf®) is an oral preparation derived from Lumbricus rubellus with fibrinolytic and potential anti-inflammatory properties. Participants in the experimental group received DLBS1033 490 mg as one oral tablet twice daily (total daily dose: 980 mg), in addition to standard medical treatment for pneumonia complicated by sepsis and hypercoagulability. The intervention was administered during hospitalization until clinical stability was achieved according to Halm's Criteria.

Also known as: Lumbrokinase, Earthworm Extract, Lumbricus rubellus enzyme

Standard Therapy + Lumbrokinase DLBS1033

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients aged 18 years or older.
• Patients diagnosed with community-acquired pneumonia (CAP) or hospital-acquired pneumonia (HAP) complicated by sepsis.
• Patients meeting sepsis assessment criteria based on the Sequential Organ Failure Assessment (SOFA) or quick Sequential Organ Failure Assessment (qSOFA).
• Patients with elevated D-dimer levels of at least twice the upper limit of normal (≥1,000 ng/mL FEU), indicating a hypercoagulable state.
• Patients who had not yet received specific treatment targeting severe pneumonia and sepsis at the time of recruitment.
• Patients with a Charlson Comorbidity Index (CCI) score below 4.
• Patients who voluntarily agreed to participate and provided written informed consent.

You may not qualify if:

• Patients requiring a nasogastric tube (NGT), because the oral Lumbrokinase DLBS1033 formulation cannot be crushed or administered through an NGT.
• Pregnant or breastfeeding women.
• Patients with a history of severe allergic reactions to earthworm extracts or any component of Lumbrokinase DLBS1033.
• Patients with other active infections or serious medical conditions that could interfere with the clinical evaluation of pneumonia and sepsis.
• Patients with unstable comorbid conditions, including diabetes mellitus with acute hyperglycemia or an active myocardial infarction.
• Patients with a Charlson Comorbidity Index (CCI) score of 4 or higher.

Sponsors & Collaborators

• Universitas Sebelas Maret: lead

Study Sites (1)

Dr. Moewardi General Hospital, Faculty of Medicine, Universitas Sebelas Maret (UNS)

Surakarta, Central Java, 57126, Indonesia

Location

Related Publications (5)

• Bastrup Israelsen S, Fally M, Brok Nielsen P, Kolte L, Karmark Iversen K, Ravn P, Benfield T. Reassessing Halm's clinical stability criteria in community-acquired pneumonia management. Eur Respir J. 2024 Nov 7;64(5):2400054. doi: 10.1183/13993003.00054-2024. Print 2024 Nov.

  PMID: 39174283 BACKGROUND

• Gayatri A, Nafrialdi N, Setiabudy RD, Tjandrawinata RR, Rachman A, Louisa M. A Clinical Trial on Biological Half Life of Bioactive Protein from Lumbricus rubellus, DLBS1033 in Healthy Volunteers. Acta Med Indones. 2018 Jul;50(3):208-214.

  PMID: 30333270 BACKGROUND

• 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: 33927846 BACKGROUND

• Tjandrawinata RR, Trisina J, Rahayu P, Prasetya LA, Hanafiah A, Rachmawati H. Bioactive protein fraction DLBS1033 containing lumbrokinase isolated from Lumbricus rubellus: ex vivo, in vivo, and pharmaceutic studies. Drug Des Devel Ther. 2014 Sep 25;8:1585-93. doi: 10.2147/DDDT.S66007. eCollection 2014.

  PMID: 25284988 BACKGROUND

• 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 BACKGROUND

MeSH Terms

Conditions

Pneumonia; Sepsis; Blood Coagulation Disorders; Thrombophilia

Interventions

DLBS 1033; lumbrokinase

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Eldaa Putik Bunga Melati, MD

  Faculty of Medicine of Universitas Sebelas Maret (UNS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This study used a double-blind design in which participants and study investigators were unaware of treatment allocation. Participants received either oral Lumbrokinase DLBS1033 or matching placebo in addition to standard medical treatment. Treatment allocation was based on a randomized sequence, and the assigned interventions were concealed from participants and investigators during the blinded study period.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This study employed a randomized, double-blind, placebo-controlled, two-arm parallel-group design. A total of 50 participants were randomly assigned in a 1:1 ratio to receive either standard therapy plus oral Lumbrokinase DLBS1033 (n=25) or standard therapy plus placebo (n=25). Participants remained in their assigned treatment groups throughout the study. D-dimer and interleukin-6 levels were assessed at baseline (H0), day 10 (H10), and a clinical stability-related assessment (H+1). Time to clinical stability and length of hospital stay were also evaluated.

Study Record Dates

• First Submitted: October 12, 2026
• First Posted: October 23, 2026
• Study Start: August 14, 2025
• Primary Completion: September 23, 2025
• Study Completion: September 30, 2025
• Last Updated: October 23, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will not share

Locations

ID (1)