Pre- and post-surgical medical treatment of human cystic echinococcosis
| ISRCTN | ISRCTN78387420 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN78387420 |
| Secondary identifying numbers | U1111-1295-7209 |
- Submission date
- 25/07/2023
- Registration date
- 02/08/2023
- Last edited
- 19/10/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English Summary
Background and study aims
Cystic echinococcosis (CE) is a chronic disease and is considered a neglected one. It is a parasitic disease caused by tapeworms and is endemic in Uruguay and the region. Surgery, using various technical approaches, has the potential to safely remove the cyst(s) and lead to a complete cure in a high number of patients with simple forms of CE. However, surgery may be impractical in patients with multiple cysts in several organs, high surgical risk, or in patients with previous multiple surgeries. In these cases, treatment with the drug albendazole (ABZ) alone or combined with praziquantel (PZQ), has been promising as the best choice to achieve improvement or cure. This is a follow-up study of symptomatic cystic echinococcosis treatment with albendazole and praziquantel in Uruguay.
Who can participate?
Patients aged 15 to 65 years with cystic echinococcosis
What does the study involve?
A discontinuous treatment: 30 days treatment with a 15-day break between two 7-day courses of the corresponding drug was basically used in all patients from the beginning until the end of the study.
The standardized drug treatments before surgery were 7 days, 15 days or 1 month. The standardized drug treatment after surgery was six cycles of the 30/15 treatment protocol. The drug was ABZ in all cases, administered orally, twice daily, at a total dosage of 15 mg/kg/day, with food high in fat content for improved absorption. When possible, including in underdeveloped suburban and rural areas of the country, tests including blood and liver tests were used to assess potential side effects of the ABZ and evaluate the general clinical state of every patient. In cases of verified ABZ toxicity, the dosage was immediately lowered to 7.5 mg/kg/day and the tests run weekly until the values normalized. In case of continuing blood alterations, ABZ was suspended until all the abnormal values disappeared. Only then, ABZ delivery was resumed at 7.5 mg/kg/day, associated with PZQ at a dosage of 40 mg/kg/day, allowing the follow-up to continue with frequent monitoring of blood and liver parameters.
In abdominal cases, a follow-up ultrasound was performed every 3 months in the first year and a CT 1 year after finishing treatment. Subsequent control was performed with annual CT. The images were analyzed to determine the size and status of individual cysts.
What are the possible benefits and risks of participating?
There is a risk that albendazole causes leukopenia and transaminasemia, which leads to suspension of treatment and changing to praziquantel, which has no side effects, this being a second-choice drug.
Where is the study run from?
University of the Republic (Uruguay)
When is the study starting and how long is it expected to run for?
August 2003 to December 2020
Who is funding the study?
University of the Republic (Uruguay)
Who is the main contact?
Assistant Prof. Dr Walner Daniel Da Rosa, ddarosa@higiene.edu.uy, danddr@gmail.com
Contact information
Principal Investigator
Avda Alfredo Navarro 3051 3er floor
Montevideo
11600
Uruguay
 ORCID ID |
0000-0001-8735-0334 |
|---|---|
| Phone | +598 (0)2094426568 |
| ddarosa@higiene.edu.uy |
Study information
| Study design | Prospective clinical trial non-randomized study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Medical and other records |
| Study type | Treatment |
| Scientific title | Follow-up study of symptomatic human cystic echinococcosis treatment with albendazole and praziquantel in Uruguay |
| Study acronym | FUHCE |
| Study hypothesis | Treatment of symptomatic patients with cystic echinococcosis pre and postoperatively using albendazole and praziquantel with 5-year imaging follow-up. |
| Ethics approval(s) |
Approved 21/10/2020, The Ethics Committee of the School of Medicine, UDELAR (Gral. Flores 2125 Código Postal, Montevideo, 11800, Uruguay; (+598-2) 924 3414 - Int: 3363; comisiones@fmed.edu.uy), ref: 501115-002-20 |
| Condition | Cystic echinococcosis |
| Intervention | A discontinuous treatment: 30 days treatment with a 15-day break between two 7-day courses of the corresponding drug was basically used in all patients from the beginning until the end of the study. The standardized drug treatments before surgery were 7 days, 15 days or 1 month. The standardized drug treatment after surgery was six cycles of the 30/15 treatment protocol. The drug was ABZ in all cases, administered orally, twice daily, at a total dosage of 15 mg/kg/day, with food high in fat content for improved absorption. When possible, including in underdeveloped suburban and rural areas of the country, the biological fluid tests included blood count and complete functional hepatic to visualize potential side effects of the ABZ and evaluation of the general clinical state of every patient. Minimally, the researchers requested hematological determinations to assess leukopenia (≤5000 leukocytes) and hypertransaminasemia of ≤150 U/L, a number over three times the GOT and GPT normal values according to age and sex. In cases of verified ABZ toxicity, the dosage was immediately lowered to 7.5 mg/kg/day and the blood count and functional hepatic test run weekly until the values normalized. In case of continuing hematological alterations and/or hypertransaminasemia; ABZ had to be suspended until all the abnormal values disappeared. Only then, ABZ delivery was resumed at 7.5 mg/kg/day, associated with PZQ at a dosage of 40 mg/kg/day, allowing the follow-up to continue with frequent monitoring of blood and liver parameters. Follow-up and treatment efficacy In abdominal cases, a follow-up ultrasound was performed every 3 months in the first year and a CT one year after finishing treatment. Subsequent control was performed with annual CT. Priority for the imaging studies was given to the same professional who produced the original results; using the same conditions to consider the images comparative in the follow-up. The images were analyzed to determine the size and status of individual cysts (standards classification of WHO-IWGE). The treatment effectiveness is defined as resolution or not resolution considering imaging evolution 5 years after the end of the initial pharmacological therapy, per patient and status of cysts. The criteria to determine effective therapy was constructed from the standard classification by WHO-IWGE. Individual cysts and patients were classified as achieving success (cure or marked improvement), or no success (no change or worsening). Cure was defined as the disappearance of the cyst(s) determined by TC parameters; marked improvement was defined as ≥25% reduction of the cyst size; both definitions required a transition to inactive phases (CE4, CE5) in the follow-up evaluation. Statistical analysis All the patient clinical and laboratory data were analyzed by Epi Info 2000 (Center for Disease Control, Atlanta, Georgia, USA). Data were described as mean value ± SD or frequency and percentage when appropriate. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Not Applicable |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Albendazole, praziquantel |
| Primary outcome measure | Size of the cyst measured by computed tomography (CT) or nuclear magnetic resonance (NMR) at 5 years of follow-up |
| Secondary outcome measures | Stage of the cyst measured by computed tomography (CT) or magnetic resonance imaging (MRI) from active (CE1, CE2) to inactive (CE4 and CE5) stages during medical treatment at 5-year follow-up |
| Overall study start date | 08/08/2003 |
| Overall study end date | 20/12/2020 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 15 Years |
| Upper age limit | 65 Years |
| Sex | Both |
| Target number of participants | 43 |
| Total final enrolment | 36 |
| Participant inclusion criteria | 1. Patients were recruited from January 2003 to October 2020 from different hospitals throughout Uruguay who completed the 5 years post-treatment follow-up in October 2020 2. Patients with cystic echinococcosis diagnosis, based on clinical symptoms, morphological features detected by imaging techniques (RX, US, CT, MR) and immunologic tests (indirect hemagglutination [IHA], indirect immunofluorescence [IFI]) 3. Less or equal cysts size to 7 cm, remnants post-surgical act, high surgical risk or multiple locations 4. Stage CE1, CE2 o CE3a o CE3b |
| Participant exclusion criteria | 1. Patients who did not fulfil the follow-up criteria 2. Surgical treatment: Patients with low or moderate surgical risk and cysts larger than 7 cm, were subjected to surgery. However, the protocols require mandatory surgery for any cysts with a pulmonary location. |
| Recruitment start date | 01/09/2003 |
| Recruitment end date | 18/12/2015 |
Locations
Countries of recruitment
- Uruguay
Study participating centre
Montevideo
11600
Uruguay
Sponsor information
University/education
Facultad de Medicina, Udelar
Gral. Flores 2125
Montevideo
11800
Uruguay
| Phone | (+598-2) 924 3414 - Int: 3363 Fax: (+598-2) 924 3414 - Int: 3362 |
|---|---|
| comisiones@fmed.edu.uy | |
| Website | http://www.gineb.fmed.edu.uy/institucional/consejo/consejo-de-facultad |
"ROR" |
https://ror.org/030bbe882 |
Funders
Funder type
University/education
Private sector organisation / Universities (academic only)
- Alternative name(s)
- University of the Republic Uruguay, University of the Republic, Universidad de la República, UdelaR
- Location
- Uruguay
Results and Publications
| Intention to publish date | 31/12/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | The study has been presented at international conferences on cystic echinococcosis in 2019 in Argentina |
| IPD sharing plan | The datasets generated and/or analyzed during the current study are not expected to be available due to reasons of strict confidentiality with both the patients and the participating colleagues. |
Editorial Notes
19/10/2023: Ethics approval details added. The intention to publish date was changed from 20/09/2023 to 31/12/2023.
02/08/2023: Study's existence confirmed by the Ethics Committee of the School of Medicine, UDELAR.
