Use of interferon gamma as adjuvant to chemotherapy in patients with pulmonary atypical mycobacteriosis
ISRCTN | ISRCTN70900209 |
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DOI | https://doi.org/10.1186/ISRCTN70900209 |
Secondary identifying numbers | IG/IGI/MB/0101 |
- Submission date
- 14/02/2007
- Registration date
- 21/02/2007
- Last edited
- 05/01/2021
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Dr María Teresa Milanés-Virelles
Scientific
Scientific
Hospital Benéfico Jurídico
Calzada del Cerro No.1652
Cerro
Havana
10800
Cuba
Phone | +53 (0)7 404256 |
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mariateresam@infomed.sld.cu |
Study information
Study design | Randomised, double-blind, placebo controlled, parallel group trial |
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Primary study design | Interventional |
Secondary study design | Randomised controlled trial |
Study setting(s) | Not specified |
Study type | Treatment |
Scientific title | Use of interferon gamma as adjuvant to chemotherapy in patients with pulmonary atypical mycobacteriosis |
Study acronym | MACGAM-I |
Study objectives | Mycobacteriosis refers to infection by any member of a group of ubiquitous environmental mycobacteria. Mycobacterium Avium Complex (MAC) is the most frequent. It can produce a wide range of disease: Disseminated MAC disease (DMAC) in immunocompromised individuals and MAC Pulmonary Disease (MAC-PD) in immunocompetent adults. MAC disease is associated with substantial morbidity and mortality. Although DMAC rates declined dramatically after 1995 with the introduction of highly active antiretroviral therapy, pulmonary physicians observed an increase in MAC-PD among Human Immunodeficiency Virus (HIV)-negative patients in the late 1990s and early 2000s. The optimal treatment regimen for MAC-PD has not been fully established. The most clinically efficacious drugs for the treatment of MAC are the new macrolide or azalide antibiotics, clarithromycin or azithromycin, respectively. These drugs are generally part of a multidrug regimen that includes rifamycin and ethambutol. This regimen becomes expensive, is poorly tolerated, and can lead to a variety of side effects. Interferon gamma can enhance the hosts defense mechanism and thus contribute to disease clearance. Hypothesis: Adjuvant interferon gamma will increase overall response rate to treatment from 30% in the placebo group to 90%. |
Ethics approval(s) | Approval received from the Ethics Committee of the Benefico Juridico Hospital, Havana, and the Amalia Simoni Hospital, Camaguey. Also approved by the Cuban Regulatory Authority (CECMed) on the 18th March 2002 (ref: 43/05-041-01-B). |
Health condition(s) or problem(s) studied | Mycobacteriosis |
Intervention | Two parallel groups: Group one: Antibiotic chemotherapy and interferon gamma Group two: Antibiotic chemotherapy and placebo Treatment lasted six months, and a further follow up of 12 months occurred. Evaluations were performed at the end of the treatment (six months) and end of the follow up (18 months). Treatment schedule consists of 1 million IU of human recombinant interferon gamma (produced in E. coli, specific activity: 1 x 10^7 IU/mg of proteins [Heberon Gamma R, Heber Biotec, Havana]) or placebo intramuscularly, daily during four weeks and then three times per week for the next 20 weeks. All the patients will receive the same conventional antibiotic schedule, orally, daily as follows: azithromycin 500 mg, ciprofloxacin 1000 mg, rifampin 600 mg, and ethambutol 2000 mg. |
Intervention type | Drug |
Pharmaceutical study type(s) | |
Phase | Not Specified |
Drug / device / biological / vaccine name(s) | Human recombinant interferon gamma, azithromycin, ciprofloxacin, rifampin, and ethambutol. |
Primary outcome measure | Composite variable that includes clinical, bacteriological and radiological outcomes: 1. Complete response: a. disappearance of all symptoms b. negative sputum acid-fast-bacilli smear and culture c. pulmonary lesions improvement at X-ray 2. Partial response: a. symptoms decrease b. negative sputum smear and culture c. stable or improvement at X-ray 3. No response: a. symptoms persistence b. positive bacteriological examinations c. lesion progression at X-ray |
Secondary outcome measures | 1. General clinical status: a. good: none or discreet respiratory symptoms without frequent or serious exacerbations, appropriate body weight b. moderate: maintained respiratory symptoms with more acute exacerbations, appropriate body weight c. bad: maintained serious respiratory symptoms (intense dyspnea, cough, and abundant expectoration), low body weight 2. Dyspnea perception: a. score 0: no dyspnea at all b. score 1: dyspnea while climbing hills or stairs c. score 2: dyspnea while walking at a rapid pace on ground level d. score 3: dyspnea while walking at own pace on ground level e.score 4: dyspnea at rest 3. Bacteriology: sputum direct observation and culture: positive or negative 4. Radiology: a. lesions extension: i. minimum: if they comprised up to one third of a lung area ii. moderate: up to one lung involvement iii. advanced: more than one lung involved b. presence of cavitations 5. Time to overall and each response 6. Clinical laboratory variables: a. haematocrit b. globular sedimentation rate |
Overall study start date | 07/10/2002 |
Completion date | 29/09/2005 |
Eligibility
Participant type(s) | Patient |
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Age group | Adult |
Lower age limit | 18 Years |
Sex | Not Specified |
Target number of participants | 34 |
Total final enrolment | 32 |
Key inclusion criteria | 1. Patient's written informed consent 2. To fulfil diagnostic criteria: a. isolation and typification, at least three times, in sputum samples of any of the following species: M. Avium-intracellulare, M. Kansasii, M. Xenopi, M. Marinum, M. fortuitum-chelonae, M. simiae, M. Scrofulaceum, M. Szulgai, M. Gorddonae, M. Flavescans, M. Gastri, M. Triviale, M. Vaccae, M. Smegmatis or M. Phlei b. presence of respiratory symptoms such as cough and expectoration c. tuberculosis-like lesions at thorax radiography 3. Aged more than 18 years old 4. In case of fertile women, to use a non-hormone anti-conception method 5. Not having received any type of interferon during the previous three months |
Key exclusion criteria | 1. Any other respiratory infection 2. Severe cardiovascular disease 3. Renal or liver failure 4. Malignancies, except for skin basal cell carcinoma and in situ cervix carcinoma 5. Pregnancy or breast-feeding 6. Human Immunodeficiency Virus (HIV) co-infection 7. Hypersensitivity to interferon or other components of the formulations used 8. Treatment with glucocoticoids or other immunosuppressor medication 9. Functional central nervous system alterations 10. Multiple sclerosis or other auto-immune disease |
Date of first enrolment | 07/10/2002 |
Date of final enrolment | 29/09/2005 |
Locations
Countries of recruitment
- Cuba
Study participating centre
Hospital Benéfico Jurídico
Havana
10800
Cuba
10800
Cuba
Sponsor information
Centre for Genetic Engineering and Biotechnology (Centro de Ingeniería Genética y Biotecnología) (Cuba)
Research organisation
Research organisation
Ave. 31 entre 158 y 190
Cubanacán, Playa
Havana
11600
Cuba
Phone | +53 (0)7 2716022 |
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lopez.saura@cigb.edu.cu | |
Website | http://www.cigb.edu.cu |
https://ror.org/03qxwgf98 |
Funders
Funder type
Research organisation
Centre for Genetic Engineering and Biotechnology (Cuba)
No information available
Ministry of Public Health (Cuba)
Government organisation / National government
Government organisation / National government
- Alternative name(s)
- Ministry of Public Health (Thailand), กระทรวงสาธารณสุข, MOPH
- Location
- Thailand
Results and Publications
Intention to publish date | |
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Individual participant data (IPD) Intention to share | No |
IPD sharing plan summary | Not provided at time of registration |
Publication and dissemination plan | Not provided at time of registration |
IPD sharing plan |
Study outputs
Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
---|---|---|---|---|---|
Results article | results | 11/02/2008 | 05/01/2021 | Yes | No |
Editorial Notes
05/01/2021: Publication reference and total final enrolment added.