Observation and Treatment of Pulmonary Microthrombosis in Childhood Pneumonia With Elevated D-dimer

Sponsor

Capital Institute of Pediatrics, China (Other)

Overall Status

Completed

CT.gov ID

NCT04778917

Collaborator

(none)

124

Enrollment

Location

Arms

Duration (Months)

3.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Objective

Master the clinical feathers, imaging features and laboratory diagnosis characteristics and economic costs of children pneumonia with higher D-dimer:
Compare the characteristics of different groups of children in the course of the disease，clinicalsymptoms and signs;
All the children in the study need to do enhanced CT, to observe if there were intrapulmonary vascular thrombosis and necrosis pneumonia signs;
compared changes of coagulation index beside D-dimer.
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.

Condition or Disease	Intervention/Treatment	Phase
Pneumonia	Drug: Low-Molecular-Weight Heparins Calcium Injection	Phase 4

Detailed Description

This is a randomized, controlled, single blind trial(Researchers are not blind, patients are blind).

1.Patient population

.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.
.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:

.Compare the group A with the control group of the clinical features
. Compare all of the patients in the observation group with the control group of the chest CT features
.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.

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

124 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Treatment

Official Title:

Observation and Treatment of Pulmonary Microthrombosis in Childhood Pneumonia With Elevated D-dimer

Study Start Date :

Dec 1, 2014

Actual Primary Completion Date :

Jul 1, 2017

Actual Study Completion Date :

Feb 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Small dose low molecular weight heparin Low molecular weight heparin calcium 100 units / kg/day, subcutaneous injection, 5-10 days of treatment or D-dimer recovery normal.	Drug: Low-Molecular-Weight Heparins Calcium Injection We use different dose of low-molecular-weight heparins calcium injection to different interventions
Experimental: High dose of low molecular weight heparin low molecular weight heparin calcium 200 units /kg/day, subcutaneous injection, treatment for 7 days or D-dimer return to normal.	Drug: Low-Molecular-Weight Heparins Calcium Injection We use different dose of low-molecular-weight heparins calcium injection to different interventions
Placebo Comparator: Vacuity contrast group Conventional treatment for children with pneumonia, without the use of low molecular weight heparin.	Drug: Low-Molecular-Weight Heparins Calcium Injection We use different dose of low-molecular-weight heparins calcium injection to different interventions
No Intervention: contrast group Conventional treatment for children with pneumonia, without the use of low molecular weight heparin.

Outcome Measures

Primary Outcome Measures

Lung imaging absorption improvement time after treatment [Change from basline in lung imaging at 1 month]
The enrolled children were subjected to weekly imaging examinations to determine the time for the absorption of lung inflammation to improve.Criteria for evaluating the severity of CT changes (large lung shadows or dot shadows in CT images) : Criteria for improvement of lung imaging absorption: no obvious lesion absorption, no absorption or large patchy shadow; Partial absorption of lesions: there is absorption, but there is still patchy shadow or cloud flocculent shadow; Obvious absorption of lesions: no abnormalities or only a little light in the lung.
Time to improve cough symptoms [2 weeks]
The clinician will judge the improvement time of the child's cough symptoms
Heat retreat time [2 weeks]
The time required for temperature to drop below 37.3℃ after treatment.
The time to disappear rhonchus in the lungs [2 weeks]
The clinician will judge the absorption time of dry and wet rhonchus in the lungs.

Secondary Outcome Measures

Average hospital stay time [2weeks to 4weeks]
The time required from the child's admission to the improvement and discharge
The degree of coagulation improvement [2 weeks]
Laboratory test indicators include: platelet count (PLT), prothrombin time, partial thromboplastin time Prothrombin time（PT）\Activated partial thromboplastin time（APTT）, protein fiber, fiber protein degradation product Fibrinogen（FIB）\Fibrinogen degradation products（FDP）, D-dimer, Antithrombin III（AT-III）.Compare the improvement degree of the above indicators in each group before and after treatment.
Differences in inflammation indicators in each group [basline]
The inflammatory markers included CRP, ESR and WBC counts.