Clinical trial NCT04778917: Observation and Treatment of Pulmonary Microthrombosis in Childhood Pneumonia With Elevated D-dimer
Official title: Observation and Treatment of Pulmonary Microthrombosis in Childhood Pneumonia With Elevated D-dimer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pneumonia
Keywords: D-dimer,pneumonia,children
Lead sponsor: Capital Institute of Pediatrics, China
Sponsor class: OTHER
First posted: 2021-03-03
Enrollment: 124
Sex: ALL
Minimum age (years): 28
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of simple pneumonia
* Age 28 days to 18 years

Exclusion Criteria:

* With congenital heart disease
* With kidney disease
* With blood system diseases
* With paralysis
* With muscle tension
* With fracture,
* With a family history of thrombotic disease
* With indwelling central venous catheters
* With parenteral nutrition, neoplastic disease
* With primary immunodeficiency disease

Primary outcomes:
measure: Lung imaging absorption improvement time after treatment
timeFrame: Change from basline in lung imaging at 1 month
measure: Time to improve cough symptoms
timeFrame: 2 weeks
measure: Heat retreat time
timeFrame: 2 weeks
measure: The time to disappear rhonchus in the lungs
timeFrame: 2 weeks
Secondary outcomes:
measure: Average hospital stay time
timeFrame: 2weeks to 4weeks
measure: The degree of coagulation improvement
timeFrame: 2 weeks
measure: Differences in inflammation indicators in each group
timeFrame: basline
Other outcomes:
Locations:
city: Beijing
country: China
facility: Capital Institute of Pediatrics
Study officials:
affiliation: Capital Institute of Pediatrics, China
name: Ling Cao, MD
role: PRINCIPAL_INVESTIGATOR
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