Observation and Treatment of Pulmonary Microthrombosis in Childhood Pneumonia With Elevated D-dimer
Condition: Pneumonia
MeSH terms: Pneumonia
Study type: Interventional
Phase: Phase 4

Summary: 
      Objective

      1. Master the clinical feathers, imaging features and laboratory diagnosis characteristics
      and economic costs of children pneumonia with higher D-dimer:

        1. Compare the characteristics of different groups of children in the course of the
           disease，clinicalsymptoms and signs;

        2. All the children in the study need to do enhanced CT, to observe if there were
           intrapulmonary vascular thrombosis and necrosis pneumonia signs;

        3. compared changes of coagulation index beside D-dimer.

      2. Compared with low molecular weight heparin prevention Disseminated intravascular
      coagulation（DIC） dose and instructions to the recommended dose in safety and
      effectiveness,and proposed elevated anticoagulation D-Dimer specification of the clinical
      treatment of children with pneumonia.

      Background and rationale:

      Pneumonia is the main cause of lung function injury and death in children. The high blood
      coagulation state can lead to the formation of pulmonary vascular thrombosis, local pulmonary
      ischemia and necrosis, which may be an important mechanism for the occurrence of necrotizing
      pneumonia and pulmonary embolism in children with pneumonia. Elevated D-dimer is an important
      predictor of pulmonary thrombosis and necrotizing pneumonia. At present, D-Dimer in many
      children with severe pneumonia is found to increase, the symptom is severe, the late stage of
      the performance of necrotizing pneumonia, seriously affect the children's lung function and
      quality of life.
    

Detailed description: 
      This is a randomized, controlled, single blind trial(Researchers are not blind, patients are
      blind).

      1.Patient population

        1. .Experience group We will recruit 93 cases in our trial.All of them are with simple
           pneumonia and are hospitalized in the respiratory department of our hospital, also
           D-dimer is higher than or equal to 500ug / L, 93 cases as the observation group, were
           randomly divided into A, B, C three sub group.

        2. .Control group We will recruit 31 cases in our control group.And children in this group
           are also with simple pneumonia,they will be similar with the experience group children
           at the age, the disease course but their D-Dimer is lower than 500 ug/L.

      2.Randomized methods: A random number table was created by the statistical staff of the
      non-present research group using SAS to generate random numbers table before the start of the
      study. Selected children are in accordance with the A, B, C three groups of 1:1:1 ratio
      distribution.

      3.Study method: Fasting venous blood was extracted from all the children from the second
      morning after admission to complete the coagulation function, blood routine, biochemical and
      related inflammatory indicators and complete chest CT examination。The above indicators were
      monitored dynamically during hospitalization.

      4.Study protocal:

      Study group:

      Group A :Conventional treatment for children with pneumonia, without the use of low molecular
      weight heparin.

      Group B :Group B with prevention of DIC amount: low molecular weight heparin calcium 50-100
      units / kg, once or twice subcutaneous injection, 5-10 days of treatment or D-Dimer recovery
      normal. According to Huang Ke, disseminated intravascular coagulation, Huang Shaoliang, Zhou
      Dunhua, editor in chief of pediatric hematology clinical manual, Third Edition, 601-602.

      Group C :Group C with anticoagulant therapy: low molecular weight heparin calcium 100 units
      /kg, subcutaneous injection, two times a day, treatment for 7 days orD-Dimer return to
      normal. Low molecular weight heparin calcium.

      Control group :Conventional treatment for children with pneumonia, without the use of low
      molecular weight heparin.

      5.Statistical methods

      Statistical analysis system(SAS).2 software was used for statistical analysis . The
      continuous variables of the central tendency and the discrete trend are represented by the
      median and the four point spacing, and the categorical variables are described by the
      constituent ratio. Normal distribution of continuous variables between the 22 comparison
      using T test, multiple comparisons using ANOVA. Non normal distribution of continuous
      variables between the 22 comparison using Rank Sum Test Wilcoxon, multiple comparisons using
      Kruskal-Wallis method. Statistical testing methods used properly. All the tests were taken by
      alpha =0.05.

      6.Study objection:

        1. .Compare the group A with the control group of the clinical features

        2. . Compare all of the patients in the observation group with the control group of the
           chest CT features

        3. .To observe the efficacy and safety of anticoagulant therapy to children with D-dimer
           increased pneumonia

      7.Sample size estimation：

      As there is no evaluation of the efficacy of children with pneumonia combined with elevated
      D-Dimer in China, studies have shown that severe pneumonia is often accompanied by elevated
      D-Dimer. Therefore, this study only estimates the sample size based on the effective rate of
      heparin in the treatment of severe pneumonia. According to Wang Xuanzhu's research [Wang
      Xuanzhu. The efficacy of heparin in the treatment of severe pneumonia in children and its
      effect on platelet parameters and D-dimers], the effective rate of conventional methods in
      the treatment of severe pneumonia is 76.6%, and the effective rate of low-dose heparin
      treatment is 95.8%. This study adopts a two-sided test, taking α=0.05, β=0.20, u0.05/2=1.96,
      u0.2=0.8, p1=0.766, p2=0.958.Considering the possible loss to follow-up rate in this study is
      10%, the sample size of each group should be: 31.

      8. Reporting for adverse events

      Liver function, coagulation function, and platelet monitoring were performed for each child
      in the group. If there is a tendency to bleeding, the test was immediately terminated and
      corresponding treatment was given.
    

Intervention name(s): Low-Molecular-Weight Heparins Calcium Injection
Intervention type(s): Drug
Intervention description(s): We use different dose of low-molecular-weight heparins calcium injection to different interventions
Intervention MeSH terms: Heparin; Heparin, Low-Molecular-Weight; Tinzaparin; Dalteparin; Calcium heparin; Calcium
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: D-dimer,pneumonia,children