Clinical and Immunological Efficiency of Bacterial Vaccines at Adult Patients With Bronchopulmonary Pathology

Mikhael Petrovich Kostinov

Status and phase: Completed; Phase 4

Conditions: Asthma; Chronic Obstructive Pulmonary Disease; Pneumococcal Infections

Treatments: Biological: Prevenar-13; Biological: Pneumo-23

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02787863

115030370013

Details and patient eligibility

About

Goal: to to examine the formation of postvaccination immunity and evaluate the therapeutic effect of bacterial vaccines in patients with inflammation diseases of bronchopulmonary system. Objectives of the study: assessment of microbiocenosis mucous membranes of the upper respiratory tract in patients with bronchopulmonary pathology before and after use of bacterial vaccines. Identification of mayor lymphocytes subpopulations in patients in the dynamics of the vaccination process. Study the profile of humoral immune response in patients under different schemes of vaccination. Assessment of the clinic and functional status bronchopulmonary system in the immunized patients.

Full description

Methods:

1. Immunoglobulin G (IgG)-antibodies against Streptococcus pneumoniae (S. pneumoniae) - solid-phase enzyme-linked immunoelectrodiffusion essay (ELISA).

2. General levels of Immunoglobulin A (IgA), Immunoglobulin M (IgM), IgG, Immunoglobulin E (IgE) in sera - radial immunodiffusion.

3. Phagocytic activity (granulocytes, monocytes), nitroblue tetrazolium test; T-lymphocytes, T-helpers (cluster of differentiation, CD3+CD4+), cytotoxic T-lymphocytes (СD3+CD8+), B-lymphocytes (CD19+); NK-cells (CD3-CD16+CD56+), NKT-cells (CD3+CD16+CD56+), activated T-cells (human leucocyte antigens, CD3+HLA DR+), CD3-HLA DR+.

4. Microbiological examination of sputum.

5. Determining the clinical effectiveness of vaccination.

   • the number of exacerbations of chronic bronchopulmonary pathology for the year prior to vaccination and during the first and fourth years after vaccination;
   • the number of courses of antibiotic therapy a year prior to vaccination and during the first and fourth years after immunization;
   • the number of hospitalizations for acute exacerbations of chronic bronchopulmonary disease during the year prior to vaccination and during the first and fourth years after immunization.

6. Method of estimating quality of life associated with health in patients with chronic bronchopulmonary pathology (asthma control questionnaire (ACQ-5), COPD assessment test (CAT)).

Characteristics of variables (arms 1-8).

1. The age of patients (years): mean (standard deviation) [min; median; max] for normally distributed variables; median [Q25; Q75] - for variables with distribution different from normal.

2. Gender: male/female.

3. Indicators of immune status

   • IgG antibodies to S. pneumoniae
   • IgA, g/l [0,4-3,5]
   • IgM, g/l [0,7-2,8]
   • IgG, g/l [8-18]
   • IgE, IU/ml [< 100]
   • Phagocytic index (granulocyte), % [82-90]
   • Phagocytic index (monocytes), % [75-85]
   • The participation rate of spontaneous NBT-test (neutrophils), % with intensity of 0.2.e. [7-14]
   • The index of activity induced NBT-test (neutrophils), % if intensity >of 0.36.e. [>28]
   • The percentage of NBT-positive cells in spontaneous test, % [2-19]
   • Circulating immune complexes (CEC) cond. units [0,055-0,11]
   • CD3+, % [55-80]
   • CD3+CD4+, % [31-49]
   • CD3+CD8+, % [12-30]
   • CD19+, % [5-19]
   • CD3-CD16+CD56+, % [6-20]
   • CD3+CD16+CD56+, % [<10]
   • CD3-HLA DR+, % [5-20]
   • CD3+HLA DR+, % [<12]
   • CD45RO. The reference value = 0,2.

4. Microbiological examination of sputum: frequency of selection of certain microorganisms are presented as absolute number of cases and % in the respective groups.

5. Evaluation of early post-vaccination period

   • The General condition (satisfactory/unsatisfactory)

   • Local reactions: pain (n/%), redness (n/%, cm), consolidation (n/%, cm)

   • General reactions:

     • Temperature 37,0-37,5 (n/%)
     • Temperature of 37.6-38,5 (n/%)
     • A temperature of 38.6 and > (n/%)
     • Headache (n/%)
     • Malaise, fatigue (n/%)
     • Joint pain (n/%)
     • Muscle pain (n/%)

6. Health related quality of life (HRQoL): CAT-test (for Chronic obstructive pulmonary disease (COPD) patients), ACQ-5 (for asthma patients).

Enrollment: 219 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Individuals of both sexes from 18 years with a diagnosis of COPD or Bronchial Asthma;
• The presence of signed and dated informed consent to participate in a clinical study;
• The ability to perform the requirements of the Protocol;
• For women of childbearing age is a negative result of a pregnancy test before vaccination.

Diagnostic criteria for:

• COPD: dyspnea: progressive (worsens over time), increases with exertion, persistent; chronic cough (may appear sporadically and may be unproductive); chronic expectoration; the impact of risk factors in the medical history (Smoking, occupational dust pollutants and chemicals); widespread wheeze on auscultation of the chest and/or distant wheezing in the chest; family history of COPD; spirometric data confirming the presence of fixed bronchial obstruction.

Exclusion criteria

• Vaccination against pneumococcal infection in anamnesis;
• Application of preparations of immune globulin or blood transfusion within last three months prior to clinical studies;
• Prolonged use (more than 14 days) immunosuppressants or other immunosuppressive drugs within 6 months prior to the start of the study;
• Any confirmed or suspected immunosuppressive or immunodeficient condition, including Human Immunodeficiency Virus (HIV) infection;
• A history or currently hematologic and other cancers;
• A positive reaction for HIV infection, viral hepatitis B and hepatitis C;
• The presence of respiratory, cardio-vascular insufficiency, impaired liver and kidney function, established during a physical examination at visit number 1;
• Pronounced congenital defects or serious chronic diseases in the acute stage, including any clinically important exacerbation of chronic diseases of the liver, kidney, cardiovascular, nervous system, mental diseases or metabolic disorders, confirmed by the history or objective examination (pulmonary: cystic fibrosis, lung abscess, empyema, active tuberculosis; extra-pulmonary: congestive heart failure, malabsorption, chronic renal and hepatic failure, cirrhosis, malignancy, immunodeficiency, cirrhosis of the liver);
• Severe allergic reactions in anamnesis, autoimmune disease;
• The presence of acute infectious and/or communicable illnesses within 1 month prior to study;
• History of chronic alcohol abuse and/or drug use;
• Exacerbation of chronic diseases;
• Breastfeeding;
• Pregnancy;
• Participation in any other clinical study within the last 3 months.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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219 participants in 8 patient groups

COPD with Prevenar-13 (1)

Experimental group

Description:

33 patients with COPD. Standard therapy with Prevenar-13.

Treatment:

Biological: Prevenar-13

Asthma with Prevenar 13 (2)

Experimental group

Description:

34 patients with asthma. Standard therapy with Prevenar 13.

Treatment:

Biological: Prevenar-13

COPD with Pneumo-23 (3)

Experimental group

Description:

25 patients with COPD. Standard therapy with Pneumo-23.

Treatment:

Biological: Pneumo-23

Asthma with Pneumo-23 (4)

Experimental group

Description:

25 patients with asthma. Standard therapy with Pneumo-23.

Treatment:

Biological: Pneumo-23

COPD with Pneumo-23/Prevenar-13 (5)

Experimental group

Description:

32 patients with COPD. Standard therapy, vaccinated with pneumococcal polysaccharide vaccine/pneumococcal conjugate vaccine (PPV23/PCV13).

Treatment:

Biological: Pneumo-23

Biological: Prevenar-13

Asthma with Pneumo-23/Prevenar-13 (6)

Experimental group

Description:

18 patients with Asthma. Standard therapy, vaccinated with PPV23/PCV13.

Treatment:

Biological: Pneumo-23

Biological: Prevenar-13

COPD with Prevenar-13/Pneumo-23 (7)

Experimental group

Description:

25 patients with COPD. Standard therapy, vaccinated with PCV13/PPV23.

Treatment:

Biological: Pneumo-23

Biological: Prevenar-13

Asthma with Prevenar-13/Pneumo-23 (8)

Experimental group

Description:

27 patients with Asthma. Standard therapy, vaccinated with PCV13/PPV23.

Treatment:

Biological: Pneumo-23

Biological: Prevenar-13