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

Sponsor

Innogene Kalbiotech Pte. Ltd (Industry)

Overall Status

Unknown status

CT.gov ID

NCT00966628

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

2.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Dengue Shock Syndrome	Drug: Hypertonic sodium lactate Drug: Ringer's lactate	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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

Study Start Date :

May 1, 2008

Actual Primary Completion Date :

Apr 1, 2009

Anticipated Study Completion Date :

Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
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 Names: Totilac™

Arm

Intervention/Treatment

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 Names:

Totilac™

Outcome Measures

Primary Outcome Measures

To assess the effect of solution containing half molar sodium lactate (Totilac™) infusion on the plasma sVCAM-1 level [sVCAM-1 levels measured before resuscitation, after 6 hours, 12 hours, 24 hours & 48 hours post resuscitation]

Secondary Outcome Measures

To assess the effect of solution containing half molar sodium lactate (Totilac™) infusion on other efficacy and safety parameters [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.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 14 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	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