Optimal Fluid Management in Adult Severe Malaria (DRIPICCO)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by University of Oxford
Sponsor:
Information provided by (Responsible Party):
University of Oxford
ClinicalTrials.gov Identifier:
NCT01936766
First received: August 27, 2013
Last updated: August 15, 2014
Last verified: August 2014
  Purpose

Optimal fluid therapy in severe falciparum malaria has not been well defined, especially in resource poor settings where access to mechanical ventilation is limited. Recent studies suggest that liberal fluid resuscitation is harmful for severe malaria patients despite they often being hypovolemic on admission. In order to elucidate the minimum fluid therapy required to prevent complications in severe malaria, we will conduct a prospective observational study in adults with severe malaria, and also in adults with severe sepsis as a comparison group. The objective of this study is to describe the association between hemodynamic variations in conventional fluid management and the probability of developing acute kidney injury (AKI) or pulmonary edema in adults with severe malaria and severe sepsis. Hemodynamic measurements will be obtained by using transpulmonary thermodilution and arterial pulse contour analysis.


Condition
Malaria
Sepsis

Study Type: Observational [Patient Registry]
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Target Follow-Up Duration: 14 Days
Official Title: Optimal Fluid Management in Adult Severe Malaria - Development of Renal Impairment and Pulmonary Edema in Complicated Malaria Under Conventional Fluid Strategy

Resource links provided by NLM:


Further study details as provided by University of Oxford:

Primary Outcome Measures:
  • Association between the mean Global End-Diastolic Volume Index and serum creatine level and extravascular lung water index [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    The association between the mean Global End-Diastolic Volume Index (GEDVI) over the first 24 hours and (1) serum creatinine level, and (2) Extravascular Lung Water Index (EVLWI)


Secondary Outcome Measures:
  • Association between the GEDVI,after conventional fluid resuscitation, and (1) serum creatinine level, (2) EVLWI [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    The association between the GEDVI at 6, 12, 18 or 24 hours after conventional fluid resuscitation and (1) serum creatinine level, (2) EVLWI

  • Correlation between GEDVI and changes over time in plasma lactate level [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
  • Change in central venous oxygen saturation (ScvO2) in relation to GEDVI and its association with acid-base status [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
  • Incidence of pulmonary edema and ALI/ARDS [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    Incidence of pulmonary edema defined by increase of EVLWI (≥ 10 mL/kg) and ALI/ARDS in relation to proportion of blocked capillaries (observed by OPS), GEDVI and cumulative fluid administration

  • Incidence of AKI and induction rate of renal replacement therapy [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    Incidence of AKI defined by RIFLE or AKIN criteria and induction rate of renal replacement therapy in relation to proportion of blocked capillaries (observed by OPS), GEDVI and cumulative fluid balance

  • Time course of hemodynamic parameters in relation to fluid therapy [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    Time course of hemodynamic parameters, i.e. Cardiac Index (CI), Global Ejection Fraction (GEF), Stroke Volume Variation (SVV) in relation to fluid therapy

  • Time course of respiratory parameters in relation to fluid therapy [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    Time course of respiratory parameters, i.e. PaO2/FiO2 ratio, Pulmonary Vascular Permeability Index (PVPI) in relation to fluid therapy

  • Parasite burden in adults with severe malaria in relation to organ damage (renal, pulmonary) [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    Parasite burden, i.e. PfHRP2, peripheral blood parasitemia, parasite staging at enrollment in adults with severe malaria in relation to organ damage (renal, pulmonary)

  • Evaluation of Biomarkers for early detection of ARDS [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    Evaluation of Biomarkers for early detection of ARDS in both severe malaria and sepsis (plasma transferrin, albumin, others)

  • Correlation between GEDVI and clinical variables [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    Correlation between GEDVI and clinical variables including the jugular venous pressure (JVP) as a measure of volume status or passive leg raising as an indicator of fluid responsiveness

  • Evaluation of the fluid requirements for resuscitation in patients with severe malaria or sepsis [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    Evaluation of the fluid requirements for resuscitation in patients with severe malaria or sepsis, based on the optimal GEDVI defined by primary outcome measures and secondary outcome measures No. 1


Estimated Enrollment: 120
Study Start Date: June 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   16 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Patients with severe malaria or severe sepsis admitted to the secondary or tertiary care center

Criteria

Inclusion Criteria:

A. Severe Malaria

  1. Any level of asexual form of P. falciparum parasitemia on blood smear
  2. Severe malaria with one or more of the following:

    i. Cerebral malaria (GCS < 11). ii. Renal impairment (Creatinine > 2mg/dL or Anuria) iii. Hypoglycaemia (Glucose < 40mg/dL) iv. Systolic blood pressure < 80mmHg with cool extremities v. Pulmonary edema vi. Venous bicarbonate < 15mmol/L vii. Venous lactate > 4mmol/L

  3. Age 16-65 years
  4. Written informed consent obtained from patient or attending relative.

B. Severe Sepsis

  1. Negative blood smear for any Plasmodium species
  2. Clinical signs of infection with two of following:

    i. Heart rate > 90/min ii. Respiratory rate > 20/min iii. Body temperature >38°C or <36°C iv. White blood cell count of > 12000/μL or < 4000/μL

  3. Severe sepsis with one or more of the following due to infection:

    i. Systolic blood pressure < 90mmHg despite fluid resuscitation ii. Lactate > 4mmol/L iii. Urine output < 0.5mL/kg/hour for > 2 hours despite fluid resuscitation iv. Acute lung injury with PaO2/FiO2 < 250 in the absence of pneumonia v. Acute lung injury with PaO2/FiO2 < 200 in the presence of pneumonia vi. Creatinine > 2mg/dL vii. Bilirubin > 2mg/dL viii. Platelet count < 100000/μL

  4. Age 16-65 years
  5. Written informed consent obtained from patient or attending relative

Exclusion Criteria:

A. Severe Malaria

  1. Patient or relative unable or unwilling to give informed consent
  2. Serious pre-existing disease The following exclusion criteria described below are applied to patient for whom invasive hemodynamic monitoring will be performed.
  3. Spontaneous bleeding or platelet count < 30000/μL on enrollment
  4. Pregnancy.
  5. Contraindication or unsuitable condition for thermodilution technique

B. Severe Sepsis

  1. Patient or relative unable or unwilling to give informed consent
  2. Serious pre-existing disease The following exclusion criteria described below are applied to patient for whom invasive hemodynamic monitoring will be performed.
  3. Spontaneous bleeding or platelet count < 30000/μL on enrollment
  4. Pregnancy.
  5. Contraindication or unsuitable condition for thermodilution technique
  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: NCT01936766

Contacts
Contact: Arjen Dondorp, MD +66-2-203-6303 arjen@tropmedres.ac
Contact: Haruhiko Ishioka, MD +66-80-604-4255 haruhiko@tropmedres.ac

Locations
Bangladesh
Chittagong Medical College Hosiptal Recruiting
Chittagong, Bangladesh
Contact: Haruhiko Ishioka, MD    +880-178-250-5962    haruhiko@tropmedres.ac   
Sponsors and Collaborators
University of Oxford
Investigators
Principal Investigator: Arjen Dondorp, MD Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University
  More Information

No publications provided

Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT01936766     History of Changes
Other Study ID Numbers: BAKMAL 1302
Study First Received: August 27, 2013
Last Updated: August 15, 2014
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by University of Oxford:
malaria, falciparum
sepsis
fluid therapy
thermodilution
extravascular lung water
acute kidney injury

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases

ClinicalTrials.gov processed this record on September 18, 2014