AzTrials
AzTrials

Chronic Obstructive Pulmonary DiseasePhase 4NCT02787863

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

A Phase 4 study testing Prevenar-13 and Pneumo-23 in people with Chronic Obstructive Pulmonary Disease and Asthma, run by Mikhael Petrovich Kostinov at 2 sites in Russia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 80 yearsHealthy volunteers can take part
What is being tested?
Prevenar-13 and Pneumo-23
Type of treatment
Vaccines
Could I receive a placebo?
No, everyone receives an active treatment
How many people
219 participants
Where
2 sitesRussia
Study dates
6 Sep 2012to 31 Dec 2016
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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;
Show all 15Show fewer
  • 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 locations and contacts

2 sites in 1 country.

Russia2 sites

  • Institute of Sera and Vaccines RAS

    Moscow, 105064

  • Samara State Medical Univercity

    Samara, Samara Oblast, 443099

Other trials in Russia

About this study

Official title: Pathogenetic Justification and Clinical and Immunological Efficiency of Application Bacterial Vaccines at Adult Patients With Bronchopulmonary Pathology

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.

Read the 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.
  1. 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.
  1. Microbiological examination of sputum: frequency of selection of certain microorganisms are presented as absolute number of cases and % in the respective groups.
  2. 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/%)
  1. Health related quality of life (HRQoL): CAT-test (for Chronic obstructive pulmonary disease (COPD) patients), ACQ-5 (for asthma patients).
Being tested
Prevenar-13, Pneumo-23
Keywords
Pneumococcal vaccines
Medical subject headings
Pulmonary Disease, Chronic Obstructive, Asthma, Pneumococcal Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Prevenar-13Biological

    Also called PCV13

    Conjugate 13 serotype pneumococcal vaccine

  • Pneumo-23Biological

    Also called PPV23

    Polysaccharide 23-valent pneumococcal vaccine.

Study groups in NCT02787863
Study groupRoleWhat they receive
COPD with Prevenar-13 (1)Experimental33 patients with COPD. Standard therapy with Prevenar-13.
Receives: Biological: Prevenar-13
Asthma with Prevenar 13 (2)Experimental34 patients with asthma. Standard therapy with Prevenar 13.
Receives: Biological: Prevenar-13
COPD with Pneumo-23 (3)Experimental25 patients with COPD. Standard therapy with Pneumo-23.
Receives: Biological: Pneumo-23
Asthma with Pneumo-23 (4)Experimental25 patients with asthma. Standard therapy with Pneumo-23.
Receives: Biological: Pneumo-23
COPD with Pneumo-23/Prevenar-13 (5)Experimental32 patients with COPD. Standard therapy, vaccinated with pneumococcal polysaccharide vaccine/pneumococcal conjugate vaccine (PPV23/PCV13).
Receives: Biological: Prevenar-13; Biological: Pneumo-23
Asthma with Pneumo-23/Prevenar-13 (6)Experimental18 patients with Asthma. Standard therapy, vaccinated with PPV23/PCV13.
Receives: Biological: Prevenar-13; Biological: Pneumo-23
COPD with Prevenar-13/Pneumo-23 (7)Experimental25 patients with COPD. Standard therapy, vaccinated with PCV13/PPV23.
Receives: Biological: Prevenar-13; Biological: Pneumo-23
Asthma with Prevenar-13/Pneumo-23 (8)Experimental27 patients with Asthma. Standard therapy, vaccinated with PCV13/PPV23.
Receives: Biological: Prevenar-13; Biological: Pneumo-23

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Patients Without Exacerbations of the Underlying Disease, Antibiotic Use and Hospitalisation.

    Number of patients without exacerbations of the underlying disease, antibiotic use and hospitalisation.

    Measured: Baseline (1 year prior to vaccination), 1 year after vaccination, 4 years after vaccination

  2. The Number of Exacerbations of the Underlying Disease, Antibiotic Use and Hospitalisation

    The number of exacerbations of the underlying disease, antibiotic use and hospitalisation. The average number of exacerbations per 1 patient = total exacerbations in the group / number of patients in the group. This is not a mean value.

    Measured: Baseline (1 year prior to vaccination), 1 year after vaccination, 4 years after vaccination

Secondary outcomes (7)

  1. Seeding Frequency S. Pneumoniae From Sputum in Patients With COPD

    Seeding frequency S. pneumoniae from sputum in patients with COPD

    Measured: Baseline, after 1 and 4 years after vaccination

  2. Average CAT (COPD) and ACQ-5 (Asthma) Score

    CAT - COPD Assessment Test, min. = 0, max. = 40, higher scores mean a worse outcome.

    ACQ-5 - Asthma control questionnaire, min. = 0, max. = 6, higher scores mean a worse outcome.

    Measured: Baseline, after 1 and 4 years after vaccination

  3. Phagocytic Activity in Patients With COPD at Baseline, 1, 2, and 6 Weeks After PCV13 and PPV13 Vaccination

    Phagocytic index (granulocytes), phagocytic index (monocytes), activity of a spontaneous HCT test (neutrophils), activity of an induced HCT test (neutrophils), percentage of HCT-positive white blood cells in a spontaneous test. The phagocytic index was calculated according to the following formula: phagocytic index = (total number of engulfed cells/total number of counted macrophages) × (number of macrophages containing engulfed cells/total number of counted macrophages) × 100 (phagocytic index)

    The phagocytic index was calculated by counting at least 100 bacteria phagocytized by certain number of phagocytic cells/macrophages and expressed following formula (Mamnur Rashid 1997):

    Phagocytic index = Total no. of phagocytized bacteria /No of phagocytic cells phagocytizing bacteria.

    Activation index = % formazan positive cells (FPC) in NBT stimulated / % formazan positive cells (FPC) in NBT Spontaneous.

    Measured: Baseline, 1, 2, 6 weeks after PCV13 and PPV13 vaccination

  4. Immunophenotype of Blood Lymphocytes in Patients With COPD

    Immunophenotype of blood lymphocytes in patients with COPD at baseline, 1, 2 and 6 weeks after PCV13 and PPV23 vaccination. It was pre-specified to report data from only the "COPD - Prevenar-13" and the "COPD - Pneumo-23" Arms/Groups for this Outcome Measure". This is due to the fact that we tried to study the effect of PCV13 and PPV23 on immunity values. The study of the immunological effects of vaccination in the early post-vaccination period was carried out in 2 groups of patients: 20 patients with COPD vaccinated with PCV13; 20 patients with COPD vaccinated with PPV23. These patients were selected from patients of the main groups (COPD - Prevenar-13 (1), COPD - Pneumo-23 (3)).

    Measured: Baseline, 1, 2, 6 weeks after PCV13 and PPV13 vaccination

  5. IgA, IgM, IgG, IgE, Circulating Immune Complexes (CIC)

    IgA, IgM, IgG, IgE, circulating immune complexes (CIC) in serum at baseline, 1, 2 and 6 weeks after vaccination. It was pre-specified to report data from only the "COPD - Prevenar-13" and the "COPD - Pneumo-23" Arms/Groups for this Outcome Measure". This is due to the fact that we tried to study the effect of PCV13 and PPV23 on immunity values. The study of the immunological effects of vaccination in the early post-vaccination period was carried out in 2 groups of patients: 20 patients with COPD vaccinated with PCV13; 20 patients with COPD vaccinated with PPV23. These patients were selected from patients of the main groups (COPD - Prevenar-13 (1), COPD - Pneumo-23 (3)).

    Measured: Baseline, 1, 2, 6 weeks after PCV13 and PPV13 vaccination in COPD

  6. CD45RO

    CD45RO expression on lymphocytes in serum at baseline, 1 and 4 years after vaccination. These patients were selected from patients of the main groups.

    Measured: Baseline, 1 and 4 years after vaccination

  7. Specific IgG Levels in Vaccinated Patients With COPD to S. Pneumoniae Serotypes

    Mean specific IgG levels in vaccinated patients with COPD to S. pneumoniae serotypes at baseline, 6 and 12 months after vaccination

    Measured: Baseline, 1 and 12 months after vaccination

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Jun 2016 (estimated)
  2. Study start6 Sep 2012
  3. Primary completion31 Dec 2016
  4. Study completion31 Dec 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
219 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02787863
Sponsor's protocol ID
115030370013
Status last verified
Feb 2020
First submitted
20 May 2016
Last updated
25 Feb 2020
Data monitoring committee
No
Individual data sharing
No

Publications

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

  • 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.

  • 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.

  • 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

  • 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

  • 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

  • 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.

    PubMed 27239929

  • 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.

    PubMed 29488477

  • 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.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Prevenar-13 and Pneumo-23 in people with Chronic Obstructive Pulmonary Disease and Asthma, run by Mikhael Petrovich Kostinov at 2 sites in Russia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients Without Exacerbations of the Underlying Disease, Antibiotic Use and Hospitalisation. (time frame: Baseline (1 year prior to vaccination), 1 year after vaccination, 4 years after vaccination). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02787863, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2020.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in