Glutoxim in complex therapy of tuberculosis.
G.B.Sokolova,
M.V.Sinistyn, L.A.Kozhemyakin, M.I.Perelman I.M.Sechenov.
Moscow Medical Academy Phthysiopulmonology Research Institute,
In the context of tuberculosis epidemic affecting
In this situation the role of pathogenetic drugs acting to restore
patient’s reactivity becomes of increasing importance. Glutoxim, a new
metabolic immunorehabilitator, is one of such drugs.
Study objective: to evaluate the possibility and advisability of using
Glutoxim in tuberculosis patients.
Tasks:
- to evaluate the
effect of Glutoxim on the course of disseminated and severe forms of tuberculosis;
- to evaluate the
effect of Glutoxim on the course of tuberculosis in patients with multiple drug
resistance;
- to evaluate the
effect of the drug on the course of the postoperative period in tuberculosis
patients;
- to evaluate
hepatoprotective effect of Glutoxim in drug-induced and viral hepatitis in
tuberculosis patients.
Study design: open randomized (envelope method) trials. Duration of
therapy — 2 months; follow-up period — 3 months.
Study methods:
Inclusion criteria:
- either sex, 18
to 70 years old;
- primary or
chronic pulmonary tuberculosis;
- sputum positive
for the drug-susceptible (DS) or drug-resistant (DR) pathogen;
- chronic viral
hepatitis (B and C)
- drug-induced
hepatitis due to anti-tuberculosis therapy.
Exclusion criteria:
- myocardial
infarction within 12 months before therapy;
- severe angina
pectoris and heart failure;
- uncontrolled
arterial hypertension;
- psychic
disorders;
- participation in
clinical trials of other drugs within 60 days before the study;
- pregnancy and
lactation.
Study protocol:
- physical
examination (daily);
- X-ray
examination (before therapy, 2 and 4 months after the beginning of
therapy);
- luminescent
microscopy and culture test for tuberculosis mycobacteria (prior to therapy and
monthly thereafter).
- determination of
tuberculosis mycobacteria susceptibility to drugs;
- laboratory
tests: blood test; urinalysis; pigmentary, enzymatic and protein-synthetic
liver function; blood coagulation system; blood serum urea, creatinine and
glucose tests (prior to therapy and
monthly thereafter);
-
electrocardiography;
- pronchoscopy,
when indicated.
Therapy methods:
Glutoxim therapy course duration was 52 days (104 doses). The
drug was administered intravenously and intramuscularly, 1 ml of
3% solution twice a day. The drug was administered postprandially, at
Anti-tuberculosis therapy was identical in the study and the control group.
In most patients Glutoxim was introduced 2 weeks after verification of the
diagnosis of tuberculosis, following exacerbation of viral hepatitis or at
symptoms of drug-induced liver impairment. In the control group, in case of
exacerbation of viral hepatitis or at symptoms of drug-induced liver impairment
hepatotoxic anti-tuberculosis drugs were cancelled.
Glutoxim efficacy evaluation criteria (clinical, bacteriological,
roentgenological):
- tuberculosis
intoxication dynamics;
- time of sutum
conversion to negative;
- resolution of
infiltrational changes and dissemination foci, lung degradation cavern
reduction or healing;
- uncomplicated
postoperative period.
Adverse events:
Adverse events due to Glutoxim and those due to concomitantly
administered anti-tuberculosis drugs (ATD) were registered.
Clinical trials:
The study started in November, 2000. The results of treating
72 pulmonary tuberculosis patients were analyzed.
Glutoxim was administered concomitantly with ATD to 42 patients
(the study group). Of the 42 patients 12 were prepared for and underwent
successful surgery. Postoperatively they continued receiving Glutoxim for 12
more days. The control group included 30 patients on ATD. Comparative
clinical characteristics of the two groups are presented in tables 1 through 4.
Table 1.
Clinical characteristics of tuberculosis patients in the observation
groups:
|
Group |
Number of patients |
Sex |
Age |
Nature of disease |
Tuberculosis mycobacteria in sputum |
Caverns |
||
|
M |
F |
Primary |
Chronic |
|||||
|
Study |
42 |
32 |
10 |
18-50 |
29 |
13 |
37 |
32 |
|
Control |
30 |
18 |
12 |
19-50 |
22 |
8 |
28 |
27 |
Table 2.
Tuberculosis intoxication rate in the observation groups:
|
Group |
Number of patients |
Degree of tuberculosis intoxication |
||
|
Severe |
Moderate |
Absent |
||
|
Study |
42 |
29 |
10 |
3 |
|
Control |
30 |
18 |
8 |
4 |
Table 3.
Forms of pulmonary tuberculosis in the study and the control group:
|
Form of tuberculosis |
Number of patients |
Group |
|
|
Study |
Control |
||
|
Infiltrational |
17 |
10 |
7 |
|
Caseous pneumonia |
21 |
12 |
9 |
|
Disseminated |
10 |
6 |
4 |
|
Multiple tuberculomas |
11 |
6 |
5 |
|
Fibrous-cavernous |
13 |
8 |
5 |
|
Total |
72 |
42 |
30 |
Table 4.
Lung involvement by tuberculosis process in the observation groups:
|
Patient category |
Lung involvement (study
group / control group) |
|||
|
|
2 lungs |
1 lung |
1 lobe |
2 segments |
|
Primary tuberculosis |
3/1 |
7/4 |
16/14 |
3/3 |
|
Chronic tuberculosis |
3/1 |
6/2 |
3/4 |
1/1 |
|
Total |
6/2 |
13/6 |
19/18 |
4/4 |
The above tables demonstrate that patients in the study and the control group
were comparable in terms of sex, age and nature of tuberculosis process.
Tuberculosis intoxication (fever, cough, lung rales, changes in the blood
picture, weigh deficiency, menstrual disorders, depression) was observed in 39
of 42 patients in the study group and in 26 of 30 patients in the control group
(table 2).
Dynamics of intoxication symptoms disappearance are presented in
table 5.
Table 5.
Intoxication symptoms
disappearance dynamics:
|
Group |
Number of patients |
Of them with intoxication,
n/% |
Intoxication disappearance,
% |
|||
|
Month 1 |
Month 2 |
Month 3 |
Total |
|||
|
Study group |
42 |
39/92.9 |
46.2 |
35.9 |
17.9 |
100 |
|
Control group |
30 |
26/86.7 |
26.9 |
30.8 |
34.6 |
92.3 |
As seen from table 5, in the study group in the first two months
intoxication disappeared in 82.1% of cases. The respective figure in the
control group was 57.7%. Compared to the control group, patients receiving
Glutoxim demonstrated faster body temperature normalization, cough and lung
rales disappearance, normalization of peripheral blood parameters, hormonal
status normalization, potency restoration and mood improvement. During the
first two months patients in the study group had considerable gain of weight
(average 8.9 kg) compared to 4.7 kg in the control group.
Table 6 illustrates the rate and time of bacterioexcretion
termination in the observation groups.
Table 6.
Bacterioexcretion termination
rate and time:
|
Group |
Number of MBT+ patients |
MBT drug susceptibility |
Bacterioexcretion
termination, % |
|||
|
Month 1 |
Month 2 |
Month 3 |
Total |
|||
|
Study group |
37 |
DS – 20 |
35.0 |
55.0 |
5.0 |
95.0 |
|
DR – 17 |
41.2 |
41.2 |
5.9 |
88.3 |
||
|
Control group |
28 |
DS – 18 |
16.7 |
44.4 |
27.8 |
88.9 |
|
DR – 10 |
- |
40.0 |
30.0 |
70.0 |
||
The study group patients excreting ATD-sensitive, and especially
ATD-resistant, tuberculosis mycobacteria, demonstrated rapid termination of
bacterioexcretion.
According to the data of X-ray examination after 2 months, patients
receiving Glutoxim demonstrated better resolution of infiltrational changes in
the lungs, perifocal and pericavital infiltration, greater reduction in the
size of the foci and partial regression of caseous pneumonic foci compared to
the control group.
Adverse events:
3 patients receiving Glutoxim had body temperature elevation to
37.2-37.9°C. After
discontinuation of the drug for 1-2 days body temperature came back to
normal. For 3 days thereafter Glutoxim was administered at half the daily
dose, once a day. Fever did don recur and Glutoxim therapy was continued.
None of the 9 study patients with chronic hepatitis had exacerbations of
this disease, while in the control group liver disease symptoms developed in 3
of the 5 patients with chronic hepatitis. In these patients hepatotoxic drugs
were cancelled and desintoxication and symptomatic therapy given.
In five cases Glutoxim was prescribed due to the development of
drug-induced hepatitis and due to drug-induced leucosis in six more cases.
After 14-21 days of Glutoxim therapy symptoms of liver impairment disappeared
and leukocyte count returned to normal values despite continuation of ATD
therapy. In the control group hepatotoxic drugs were cancelled in 2 patients
due to drug-induced liver impairment and in 3 patients due to leucopenia.
Attempts to resume these drugs resulted in recurrence of hepatotoxic reactions
and a decrease in leukocyte count. Glutoxim therapy was effective in menstrual
cycle disorders (6 cases) and in decreased potency (5 cases). Similar
hormonal disorders in the control group persisted throughout the entire period
if intensive anti-tuberculosis therapy.
Conclusion:
The open randomized study of Glutoxim in patients with severe
disseminated drug-susceptible and drug-resistant pulmonary tuberculosis has
demonstrated high efficacy and good tolerance of the drug.
Glutoxim therapy contributes to faster resolution of tuberculosis
intoxication symptoms, sputum conversion to negative and reversion of pulmonary
inflammatory processes.
Glutoxim administration prevents exacerbations of chronic hepatitis in
tuberculosis patients, eliminated symptoms of drug-induced hepatitis and leucopenia,
normalized the menstrual cycle and increases potency without the need to cancel
ATD therapy.
Clinical use of Glutoxim has good prospects in treating tuberculosis,
especially severe drug-resistant tuberculosis accompanied by viral or
drug-induced hepatitis.
For more
references:
Dr. Giorgio Castello
Corso Torino, 32/6
16129 – Genova (Italy)
Tel: +39.010.58.94.95
Mobil
phone: +39.335.628.34.24
e-mail:
castello@tiopoietine.info