Use of interferon gamma as adjuvant to chemotherapy in patients with pulmonary atypical mycobacteriosis

ISRCTN	ISRCTN70900209
DOI	https://doi.org/10.1186/ISRCTN70900209
Protocol serial number	IG/IGI/MB/0101
Sponsor	Centre for Genetic Engineering and Biotechnology (Centro de Ingeniería Genética y Biotecnología) (Cuba)
Funders	Centre for Genetic Engineering and Biotechnology (Cuba), Ministry of Public Health (Cuba)

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

Hospital Benéfico Jurídico
Calzada del Cerro No.1652
Cerro
Havana
10800
Cuba

Phone	+53 (0)7 404256
Email	mariateresam@infomed.sld.cu

Study information

Primary study design	Interventional
Study design	Randomised, double-blind, placebo controlled, parallel group trial
Secondary study design	Randomised controlled trial
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
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Human recombinant interferon gamma, azithromycin, ciprofloxacin, rifampin, and ethambutol.
Primary outcome measure(s)	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
Key secondary outcome measure(s)	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
Completion date	29/09/2005

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Not Specified
Target sample size at registration	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

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	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.