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

NCT ID: NCT02787863

Last Updated: 2020-02-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 219 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-09-06
• Study Completion Date: 2016-12-31

Brief Summary

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.

Detailed 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).

Conditions

Chronic Obstructive Pulmonary Disease; Asthma; Pneumococcal Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

COPD with Prevenar-13 (1)

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

Group Type: EXPERIMENTAL

Prevenar-13

Intervention Type: BIOLOGICAL

Conjugate 13 serotype pneumococcal vaccine

Asthma with Prevenar 13 (2)

34 patients with asthma. Standard therapy with Prevenar 13.

Group Type: EXPERIMENTAL

Prevenar-13

Intervention Type: BIOLOGICAL

Conjugate 13 serotype pneumococcal vaccine

COPD with Pneumo-23 (3)

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

Group Type: EXPERIMENTAL

Pneumo-23

Intervention Type: BIOLOGICAL

Polysaccharide 23-valent pneumococcal vaccine.

Asthma with Pneumo-23 (4)

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

Group Type: EXPERIMENTAL

Pneumo-23

Intervention Type: BIOLOGICAL

Polysaccharide 23-valent pneumococcal vaccine.

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

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

Group Type: EXPERIMENTAL

Prevenar-13

Intervention Type: BIOLOGICAL

Conjugate 13 serotype pneumococcal vaccine

Pneumo-23

Intervention Type: BIOLOGICAL

Polysaccharide 23-valent pneumococcal vaccine.

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

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

Group Type: EXPERIMENTAL

Prevenar-13

Intervention Type: BIOLOGICAL

Conjugate 13 serotype pneumococcal vaccine

Pneumo-23

Intervention Type: BIOLOGICAL

Polysaccharide 23-valent pneumococcal vaccine.

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

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

Group Type: EXPERIMENTAL

Prevenar-13

Intervention Type: BIOLOGICAL

Conjugate 13 serotype pneumococcal vaccine

Pneumo-23

Intervention Type: BIOLOGICAL

Polysaccharide 23-valent pneumococcal vaccine.

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

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

Group Type: EXPERIMENTAL

Prevenar-13

Intervention Type: BIOLOGICAL

Conjugate 13 serotype pneumococcal vaccine

Pneumo-23

Intervention Type: BIOLOGICAL

Polysaccharide 23-valent pneumococcal vaccine.

Interventions

Prevenar-13

Conjugate 13 serotype pneumococcal vaccine

Intervention Type: BIOLOGICAL

Pneumo-23

Polysaccharide 23-valent pneumococcal vaccine.

Intervention Type: BIOLOGICAL

Other Intervention Names

PCV13; PPV23

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Mikhael Petrovich Kostinov

OTHER

Sponsor Role: lead

Responsible Party

Mikhael Petrovich Kostinov

MD, PhD, Chief of Laboratory of Vaccines and Allergotherapy of allergic diseases

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Andrei D Protasov, Professor

Role: PRINCIPAL_INVESTIGATOR

Samara State Medical University

Mikhael P Kostinov, Professor

Role: PRINCIPAL_INVESTIGATOR

Institute of Sera and Vaccines RAS, Moscow

Mikhael P Kostinov, Professor

Role: STUDY_CHAIR

Institute of Sera and Vaccines RAS, Moscow

Aleksander V Zhestkov, Professor

Role: STUDY_CHAIR

Samara State Medical University

Locations

Samara State Medical Univercity

Samara, Samara Oblast, Russia

Institute of Sera and Vaccines RAS

Moscow, , Russia

Countries

Russia

References

Protasov AD. Pneumococcal vaccination in patients with chronic broncho-pulmonary disease (literature review). The Bulletin of Contemporary Clinical Medicine. 6(2): 60-65, 2013.

Reference Type: BACKGROUND

Protasov AD, Zhestkov AV, Kostinov MP. First results of 13-valent pneumococcal conjugate vaccine treatment in patients with chronic bronchopulmonary diseases: evaluation safety and tolerability. Russian Allergology Journal 4: 18-23, 2013.

Reference Type: RESULT

Protasov AD.COMPARATIVE EVALUATION OF THE EFFECTIVENESS OF PNEUMOCOCCAL VACCINATION WITH 13-VALENT CONJUGATE AND 23-VALENT POLYSACCHARIDE VACCINE IN PATIENTS WITH COPD. Russian Allergology Journal 4: 12-17, 2014.

Reference Type: RESULT

Kostinov MP, Protasov AD, Zhestkov AV, Polishuk VB. Promising data with pneumococcal 13-valent conjugate vaccine in adult patients with chronic bronchopulmonary pathology. Pulmonology 4: 57-63, 2014

Reference Type: RESULT

Protasov AD. Comparative evaluation of the effectiveness of vaccination against pneumococcal infection in patients with bronchial asthma with the use of 13-valent conjugate and 23-valent polysaccharide vaccine. Pulmonology. 5: 52-56, 2014

Reference Type: RESULT

Kostinov MP, Zhestkov AV, Protasov AD, Kostinova TA, Pakhomov DV, Chebykina AV, Magarshak OO.Comparative analysis of dynamics of indicators of quality of life in patients with chronic obstructive pulmonary disease on the background of vaccination against pneumococcal disease using the 13-valent conjugate and 23-valent polysaccharide vaccine. Pulmonology 25(2): 163-166, 2015

Reference Type: RESULT

Protasov AD, Kostinov MP, Zhestkov AV, Shteiner ML, Magarshak OO, Kostinova TA, Ryzhov AA, Pakhomov DV, Blagovidov DA, Panina MI. [Choice of optimal vaccination tactics against pneumococcal infection from immunological and clinical standpoints in patients with chronic obstructive pulmonary disease]. Ter Arkh. 2016;88(5):62-69. doi: 10.17116/terarkh201688562-69. Russian.

Reference Type: RESULT

PMID: 27239929 (View on PubMed)

Protasov AD, Zhestkov AV, Kostinov MP, Shteiner ML, Tezikov YV, Lipatov IS, Yastrebova NE, Kostinova AM, Ryzhov AA, Polishchuk VB. [Analysis of the effectiveness and long-term results of formation of adaptive immunity in the use of various medications and vaccination schemes against pneumococcal infection in patients with chronic obstructive pulmonary disease]. Ter Arkh. 2017;89(12. Vyp. 2):165-174. doi: 10.17116/terarkh20178912165-174. Russian.

Reference Type: RESULT

PMID: 29488477 (View on PubMed)

Protasov AD, Zhestkov AV, Kostinov MP, Korymasov EA, Shteyner ML, Tezikov YV, Lipatov IS, Reshetnikova VP, Lavrent'yeva NE. Long-term clinical efficacy and a possible mechanism of action of different modes of pneumococcal vaccination in asthma patients. Pulmonology 28(2): 193-199, 2018.

Reference Type: RESULT

Other Identifiers

115030370013

Identifier Type: -

Identifier Source: org_study_id