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

ISRCTN ISRCTN70900209
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

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

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

Study information

Study designRandomised, double-blind, placebo controlled, parallel group trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Not specified
Study typeTreatment
Scientific titleUse of interferon gamma as adjuvant to chemotherapy in patients with pulmonary atypical mycobacteriosis
Study acronymMACGAM-I
Study objectivesMycobacteriosis 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 host’s 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) studiedMycobacteriosis
InterventionTwo 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 typeDrug
Pharmaceutical study type(s)
PhaseNot Specified
Drug / device / biological / vaccine name(s)Human recombinant interferon gamma, azithromycin, ciprofloxacin, rifampin, and ethambutol.
Primary outcome measureComposite 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 measures1. 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 date07/10/2002
Completion date29/09/2005

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexNot Specified
Target number of participants34
Total final enrolment32
Key inclusion criteria1. 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 criteria1. 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 enrolment07/10/2002
Date of final enrolment29/09/2005

Locations

Countries of recruitment

  • Cuba

Study participating centre

Hospital Benéfico Jurídico
Havana
10800
Cuba

Sponsor information

Centre for Genetic Engineering and Biotechnology (Centro de Ingeniería Genética y Biotecnología) (Cuba)
Research organisation

Ave. 31 entre 158 y 190
Cubanacán, Playa
Havana
11600
Cuba

Phone +53 (0)7 2716022
Email lopez.saura@cigb.edu.cu
Website http://www.cigb.edu.cu
ROR logo "ROR" 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
Alternative name(s)
Ministry of Public Health (Thailand), กระทรวงสาธารณสุข, MOPH
Location
Thailand

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot 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.