A randomised trial of the use of enterosorbents for acute intestinal infections (Aii) in children compared the effect of the treatment with three materials, PMSPH, smectite and kaolin on 148 children aged 1 month to 15 years with AII of different etiologies (Ruzhentsova et al., 2016*).
50 children received polymethylsiloxane polyhydrate (a study group), 48 took dioctahedral smectite (Comparison Group A), and 50 used colloidal silicon dioxide or kaolin (Comparison Group B). 123 children were observed at the hospital and 25 children outpatient. Most patients were under 3 years (65%). Clinical symptoms were often consistent with gastroenteritis (78%). Severe form was seen in 9% of children. Rotavirus infection was diagnosed in 55 (37%) children, norovirus in 7 (5%), salmonellosis in 18 (12%). All patients after the first examination were prescribed treatment in accordance with standard recommendations: rehydration and enterosorption therapy. No significant differences in the average duration of major symptoms (fever, appetite loss, diarrhoea, nausea) between the three groups were observed. Diarrhoea lasted 6.0 ± 0.3; 5.2 ± 0.5 and 5.8 ± 0.9 days, in the experimental group and comparison groups A and B, respectively.
No cases of individual intolerance of the polymethylsiloxane polyhydrate (Enterosgel) or refraining from its intake due to the organoleptic properties have been observed. In two cases, the taste of dioctahedral smectite was not tolerated by patients, and it has been replaced by another drug of similar action, which caused their exclusion from the study. The trial, however, did not include the placebo group. The authors did not identify the suppliers/manufacturers of the sorbents used in this study.
A similar but more comprehensive clinical study was reported in (Usenko et al., 2015*). 99 children with Aii suffering from atopic dermatitis were split in two groups. Group I of 53 patients received enterosorbent diosmectite, and Group II of 46 patients received Enterosgel. These enterosorbents were administered in standard doses recommended by the manufacturer. The control group included 26 children who did not receive enterosorbents. Most children (>82%) were under 3 years of age. More than 60% were hospitalised within 1-3 days of the disease onset. All groups received rehydration and diet treatment, and antibacterial and probiotic treatment. Among the etiological causes of the disease diarrhea-associated viruses (rotavirus, norovirus, adenoviruses) prevailed. The use of both enterosorbents produced similar results. Statistically significant improvement in the groups treated with enterosorbents was observed in terms of: clinical efficacy with higher percentage of patients relieved of most of the pathological symptoms by the end of the third day of treatment; % of full recovery; relief of symptoms of intoxication including lethargy and loss of appetite (3.1±0.41 in Group I; 3.4±0.34 in Group II vs 4.1±0.41 days in Control Group from the start of treatment); faster relief of fever (2.8±0.4; 2.9±0.4 vs 3.7±0.2 days); bloating (3.1±0.2; 2.8±0.1 vs 4.1±0.3 days); diarrhoea (3.2±0.5; 3.4±0.4 vs 4.8±0.3 days). Application of enterosorbents contributed to the complete cessation of diarrhoea by the 5th day of treatment in the of 78.5-79.3% of children, compared to 57.9% in the control group.
After 5-7 days of treatment complete clinical recovery was achieved in 73.6% of patients receiving diosmectite, and 76.1% – Enterosgel. In other patients the stools remain fluid with frequency from 3 to 6 times a day with pathological impurities; flatulence and loss of appetite were observed. In the control group, the proportion of such patients was significantly higher – 43.4% compared to 26.4% and 23.9% in Group I and Group II (p<0.05, the Fisher test).
A statistically significant shorter duration of symptoms of exicosis of I-II degree in Group II of patients treated with Enterosgel was not only in comparison with the control group, but also with Group I who received diosmectite (p<0.05, Student test). No significant difference between the two enterosorbent groups and control group was found in respect of eradicating pathogens in children suffering from atopic dermatitis. However, the inclusion of enterosorbents in the treatment of patients was associated with a statistically significant decrease of 58-63% of the frequency of exacerbation of atopic dermatitis compared with control group. It was noted that the decisive factor was the timing of the start of enterosorption: in cases of early (1-2 days of illness) start of enterosorption therapy exacerbation of atopic dermatitis was recorded only in 18.9% and 23.9% of patients of Group I and Group II, respectively, vs 42.3% in control group; when the use of enterosorbents started after 3-4 days of illness, the frequency of exacerbation of atopic dermatitis was significantly higher, 32.1 and 32.6%, respectively and was not significantly different from control group, 38.5%. The inclusion of enterosorbents in the complex therapy of AII patients had a positive impact on the severity of clinical manifestations and duration of exacerbation of atopic dermatitis, which was significantly decreased to 18.2±1.1 days in Group I and 17.3±1.8 days in Group II, vs 22.1±1.6 days in control group (p<0.05). Both groups of patients treated with enterosorbents showed a decrease in the severity of skin manifestations of allergy (swelling, redness, rash, crusting), a decrease in the intensity of pruritus, sleep disturbance, which was accompanied by a significant decrease of SCORAD index.
During the study no side effects or allergic reactions to enterosorbents were identified. The authors of the study concluded that the use of the enterosorbents for the treatment of AII in children suffering from atopic dermatitis, leads to more rapid control of symptoms of intoxication and fever, reduces the time for stool normalisation and the risk of exacerbation and the severity of clinical manifestations associated with allergic diseases in an early start of therapy.
The study presented in (Usenko et al., 2015*) had a proper control group. The authors did not identify the suppliers/manufacturers of these enterosorbents.
In the clinical trial reported in (Tkachenko et al., 2015*) the efficiency and safety of Enterosgel in the treatment of diarrhoea predominant irritable bowel syndrome (IBS-D) was studied. 30 patients with diarrhoea-predominant IBS (16 women and 14 men) were included in the study. All the patients were divided into two groups of 15 patients: the main group was treated by enterosorbent “Enterosgel” (dosage of 22.5 g, 3 times a day, 1 hour after meals for 21 days), and the reference group was treated with bismuth tripotassium dicitrate (1 tablet 3 times a day, 30 minutes before meals and 1 tablet at night for 21 days).
Manifestation dynamics of gastrointestinal complaints was assessed using the standard questionnaire and GSRS (Gastrointestinal Symptom Rating Scale) questionnaire. The GSRS is one of the two most established, validated, reliable and responsive disease-specific instruments available for assessing gastrointestinal symptoms and their impact on patients’ daily functioning (Wicklund, 1998). The questionnaire consisted of questions regarding the abdominal pain, reflux syndrome, diarrheal syndrome, dyspeptic syndrome, constipation syndrome and the total measurement scale before and after treatment. In all patients, stool form and consistency was evaluated as well (by Bristol scale) before and after treatment.
In all the patients, study of the motor-evacuation function of the gastrointestinal tract (GIT) was performed by electrogastroenterography method. No significant differences were found between the two groups in relation to the dynamics of GSRS questionnaire scale values. In patients of the main group after treatment with Enterosgel a statistically significant reduction was achieved in the severity of complaints on the scales of abdominal pain. diarrhoea syndrome, dyspeptic syndrome and on the total scale. In the reference group, the reduction of complaints was observed for all parameters studied. The most clinically significant changes observed in the Enterosgel treated group were the normalisation stool frequency and form and the decrease in bodily pain. The authors of the study claimed that such a normalisation was not observed in the group treated with the bismuth preparation however no concrete details were given. The GIT myoelectric value changes after treatment were not statistically significant in either group.
The authors concluded that Enterosgel was safe to use and efficient in the treatment of patients with diarrhoea-related IBS.
This study was conducted with a small number of patients in both groups, and there was no truly control group with placebo only treatment. The choice of the medication to compare with, bismuth tripotassium dicitrate, was unusual because it is most commonly used for the treatment of Helicobacter pylori infection in combination with antibiotics (Sun et al., 2010*).
The authors did not identify the suppliers/manufacturers of these sorbents.
Chernikhova et al., 2007, studied the effect of Enterosgel intestinal adsorption on chronic endotoxin aggression. Twenty-five volunteers (15 women and 10 men, from 25 to 65 years old) participated in the study. For 20 days, the participants took twice a day, before breakfast and lunch, one or two spoonfuls of Enterosgel. At the beginning of the study, all patients had one to three chronic diseases in remission, including adnexitis, atopic dermatitis, auto-immune thyroiditis, bronchitis, gastritis, gastroduodenitis, myocardial ischemia, urolithiasis, pancreatitis, pyelonephritis, cholecystopancreatitis. Chronic endotoxin aggression, CEA, was detected in 24 patients (96%). The blood serum level of LPS before the start of the treatment course was within normal limits (0.6 EU/ml) in one subject (4%); 1.25 EU/ml in ten patients (40%); 1.5 EU/ml in one subject (4%), 2.0 EU/ml in eight patients (32%), 2.5 EU/ml in two patients (8%), and 3.0 EU/ml in three patients (12%). The administration of Enterosgel resulted in a pronounced decrease in the blood serum concentration of endotoxin in 18 patients (75%); in 5 patients (21%) the endotoxin concentration in the blood was unchanged; and in 1 subject (4%) it increased from 1.25 to 2.0 EU/ml. Of these last six patients (25%), one subject experienced a heavy stress (a car accident the day before the final blood sampling), one had an acute excess of alcohol on the last day of the enterosorbent administration, and the others had no stressful situations or serious disturbances in the nutrition regimen. As a result of administration of Enterosgel, a number of patients with normal LPS concentration increased 7-fold, with ET serum level from 0.6 to 1.25 EU / ml has increased twofold, and with LPS concentration from 1.5 to 3.0 EU / ml – has decreased almost 5-fold, respectively. As a result of enterosorption, average ET levels in the general circulation have decreased by 56% (from 1.78 ± 0.13 to 1.13 ± 0.09). The authors concluded that Enterosgel (in monotherapy) has the ability to lower intestinal ET concentration in the bloodstream of patients with chronic inflammatory diseases.
The clinical studies described above are directly related to the treatment of diarrhoea. Although they have been published in English and Russian, they were carried out in the former USSR countries. This is hardly surprising taking into account that the original material, polymethylsiloxane (Enterosgel), was invented in the USSR in late 1980s, and registered as a medical agent for oral use under the name of Enterosgel in CIS countries. In general, intestinal sorbents in the USSR were used at a massive scale compared to the EU and other developed countries. Only latest clinical trials reported in the last 3-4 years have been reviewed here, the earlier clinical and pre-clinical studies were reviewed in Nikolaev, 2010; Nikolaev, 2011*). It is also important to note that the CIS countries effectively adopted the British system of approving the use of medicines, with the same or very similar strict regulations, and the results of the clinical trials can be accepted at their face value. Intestinal adsorbents were considered medicines, and their approval for clinical use in CIS countries means that they had to undergo relevant safety and toxicology studies (toxicity, genotoxicity, teratogenicity, mutagenicity, carcinogenicity), animal trials, pre-clinical and clinical trials before their approval for use. The same ethics rules as those used in the EU, are applied in CIS countries.