Effect of Hypertonic Sodium Lactate on sVCAM-1 Level as Surrogate Marker of Endothelial Capillary Leakage in Pediatric Dengue Shock Syndrome Patients (DSS)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2009 by Innogene Kalbiotech Pte. Ltd.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
Innogene Kalbiotech Pte. Ltd
ClinicalTrials.gov Identifier:
NCT00966628
First received: August 26, 2009
Last updated: August 27, 2009
Last verified: August 2009
  Purpose

Dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are among the leading causes of pediatric hospitalization in Asia.Mortality rates range from 1% at centres experienced in fluid resuscitation, to upto 44% in established shock.The mainstay of DSS treatment is prompt, vigorous fluid resuscitation with isotonic crystalloid solutions, followed by plasma or colloid solutions for profound or continuing shock. However, this administration is often associated with fluid overload and induces edema in these patients.

Hence, we planned a parallel, randomized controlled trial comparing the efficacy and safety of solution containing half molar sodium lactate (Totilac™) with standard treatment(isotonic crystalloid Ringer's Lactate) in pediatric Dengue Shock Syndrome patients, using plasma soluble Vascular Cell Adhesion Molecule(sVCAM-1) levels as an indicator.

Hypertonic solutions restore hemodynamic status rapidly with increased cardiac performance and improved tissue perfusion. This is obtained with much smaller volumes.We plan to assess the efficacy and safety of hypertonic sodium lactate in resuscitation of DHF/DSS patients.


Condition Intervention Phase
Dengue Shock Syndrome
Drug: Hypertonic sodium lactate
Drug: Ringer's lactate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Effect of Hypertonic Sodium Lactate on sVCAM-1 Level as a Surrogate Marker of Endothelial Capillary Leakage in Pediatric Dengue Shock Syndrome Patients

Resource links provided by NLM:


Further study details as provided by Innogene Kalbiotech Pte. Ltd:

Primary Outcome Measures:
  • To assess the effect of solution containing half molar sodium lactate (Totilac™) infusion on the plasma sVCAM-1 level [ Time Frame: sVCAM-1 levels measured before resuscitation, after 6 hours, 12 hours, 24 hours & 48 hours post resuscitation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To assess the effect of solution containing half molar sodium lactate (Totilac™) infusion on other efficacy and safety parameters [ Time Frame: Hemodynamic parameters monitored hourly. Lab parameters measured 1 hour post resuscitation and every 3 hours thereafter, based on disease severity, upto 12 hours post resuscitation. Serology exams also done at day 5 from fever onset or thereafter. ] [ Designated as safety issue: Yes ]

Enrollment: 50
Study Start Date: May 2008
Estimated Study Completion Date: December 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ringer's lactate Drug: Ringer's lactate
Ringer lactate infused at dose 20 mL/kgBW within 15 minutes to restore hemodynamic status. If shock state did not recover with first infusion, study fluid infused again at same dose. After recovery from shock, patient received maintenance dose of RL. In case of repeated shock, patients received HES (Hydroxy-Ethyl Starch) infusion at dose of 20 mL/kgBW/15-30 min with maximum dose of 50 mL/kgBW/24 hours.
Experimental: Hypertonic sodium lactate Drug: Hypertonic sodium lactate
Hypertonic sodium lactate 5 ml/kg BW administered within 15 minutes to restore hemodynamic status. If shock state did not recover with first infusion, study solution infused again at same dose. After recovery from shock state, patients receive maintenance dose at 1 mL/kgBW/hour for 12 hours. After 12 hr. infusion with study fluid, patients receive RL infusion as per standard protocol of DSS management at site.In case of repeated shock within 12 hours, study drugs can be infused again. If patient still not recovered from shock state, the patients will be given HES (Hydroxy-Ethyl Starch) infusion at dose of 20 mL/kgBW/15-30 min with maximum dose of 50 mL/kgBW/24 hours.
Other Name: Totilac™

Detailed Description:

Dengue affects an estimated 100 million people worldwide annually and is endemic in parts of Asia and the Americas, with increased incidence reported from many tropical countries recently.Dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are among the leading causes of pediatric hospitalization in Asia.Mortality rates range from 1% at centres experienced in fluid resuscitation, to upto 44% in established shock.

The mainstay of DSS treatment is prompt, vigorous fluid resuscitation with isotonic crystalloid solutions, followed by plasma or colloid solutions for profound or continuing shock. If appropriate volume resuscitation is started at an early stage, DSS is usually reversible. Patients who do not receive a proper treatment usually die within 12-24 hours after shock ensues. However, this administration is often associated with fluid overload and induces edema in these patients.

During hypovolemia in DHF/DSS, systemic hemodynamics and microcirculation are impaired, subsequently triggering a vicious cycle of progressive tissue damage that finally may lead to development of multiple organ failure. By adequately restoring intravascular volume, organ perfusion may be guaranteed, nutritive microcirculatory flow may be improved, and activation of a complex series of damaging cascades may be avoided.A solution that can rapidly restore systemic hemodynamic and improve microcirculation may be more beneficial in DHF/DSS patients.

Hypertonic solutions restore hemodynamic status rapidly with increased cardiac performance and improved tissue perfusion indicated by better urine output and tissue oxygenation. This is obtained with much smaller volumes.High lactate contained in hypertonic sodium lactate also functions as an alternate energy substrate.

However, the effects of hypertonic solution for resuscitating DHF/DSS patients have not yet investigated.Hence, we planned a parallel, randomized controlled trial comparing the efficacy and safety of solution containing half molar sodium lactate (Totilac™) with standard treatment(isotonic crystalloid Ringer's Lactate) in resuscitating pediatric Dengue Shock Syndrome patients, using plasma soluble Vascular Cell Adhesion Molecule(sVCAM-1) levels as an indicator of capillary endothelial leakage, which frequently occurs in DHF/DSS.

  Eligibility

Ages Eligible for Study:   2 Years to 14 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Pediatric patients with dengue shock syndrome
  • Ages 2-14 years
  • Resuscitation treatment naïve for DSS
  • Fulfill WHO criteria for dengue shock syndrome
  • Signed informed consent

Exclusion Criteria:

  • Patients with history of nephritic syndrome or severe renal impairment (creatinine > 2 mg/dL ), severe liver impairment (SGOT & SGPT > 2x normal), chronic diarrhea, severe malnutrition, diabetes mellitus, and history of hematological disorder based on anamnesis, physical examination, and/or lab exam.
  • Patients who are confirmed to have suffered viral or bacterial infection based on anamnesis, physical examination, and lab exam
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00966628

Locations
Indonesia
Hasan Sadikin Hospital, Dept. of Pediatrics
Bandung, West Java, Indonesia, 40161
Sponsors and Collaborators
Innogene Kalbiotech Pte. Ltd
Investigators
Study Chair: Xavier Leverve, MD, PhD INSERM-E0221-Bioenergetique Fondamentale et Appliquée Université Joseph Fourier, France
Principal Investigator: Dadang H Somasetia, SpA(K), MKes Hasan Sadikin Hospital, Dept. of Pediatrics, Bandung, Indonesia
  More Information

Publications:
Ampaiwan Chuansumrit, MD & Kanchana Tangnararatchakit, MD, Pathophysiology and management of dengue hemorrhagic fever, Journal Compilation, 2006. Transfusion Alternatives in Transfusion Medicine 8 (Suppl. 1), 3-11
Gubler DJ. Dengue and dengue haemorrhagic fever. Clin Microbiol Rev 1998; 11(Suppl 3):480-96

Responsible Party: Dr. Rikrik Ilyas, Innogene Kalbiotech Pte. Ltd., Singapore
ClinicalTrials.gov Identifier: NCT00966628     History of Changes
Other Study ID Numbers: 006/IGK-KAL/08
Study First Received: August 26, 2009
Last Updated: August 27, 2009
Health Authority: Indonesia: National Agency of Drug and Food Control

Keywords provided by Innogene Kalbiotech Pte. Ltd:
pediatric
dengue
hypertonic sodium lactate
fluid resuscitation
Ringer's lactate

Additional relevant MeSH terms:
Dengue
Shock
Severe Dengue
Arbovirus Infections
Virus Diseases
Flavivirus Infections
Flaviviridae Infections
RNA Virus Infections
Hemorrhagic Fevers, Viral
Pathologic Processes

ClinicalTrials.gov processed this record on August 19, 2014