Condition category
Infections and Infestations
Date applied
14/02/2007
Date assigned
21/02/2007
Last edited
21/02/2007
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr María Teresa Milanés-Virelles

ORCID ID

Contact details

Hospital Benéfico Jurídico
Calzada del Cerro No.1652
Cerro
Havana
10800
Cuba
+53 (0)7 404256
mariateresam@infomed.sld.cu

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

IG/IGI/MB/0101

Study information

Scientific title

Acronym

MACGAM-I

Study hypothesis

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 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

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).

Study design

Randomised, double-blind, placebo controlled, parallel group trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Condition

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 names

Human recombinant interferon gamma, azithromycin, ciprofloxacin, rifampin, and ethambutol.

Primary outcome measures

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 trial start date

07/10/2002

Overall trial end date

29/09/2005

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Not Specified

Target number of participants

34

Participant 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

Recruitment start date

07/10/2002

Recruitment end date

29/09/2005

Locations

Countries of recruitment

Cuba

Trial participating centre

Hospital Benéfico Jurídico
Havana
10800
Cuba

Sponsor information

Organisation

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

Sponsor details

Ave. 31 entre 158 y 190
Cubanacán
Playa
Havana
11600
Cuba
+53 (0)7 2716022
lopez.saura@cigb.edu.cu

Sponsor type

Research organisation

Website

http://www.cigb.edu.cu

Funders

Funder type

Research organisation

Funder name

Centre for Genetic Engineering and Biotechnology (Cuba)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Ministry of Public Health (Cuba)

Alternative name(s)

MOPH

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

Thailand

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes