A RCT of Prednisone as Adjunctive Therapy for Hospitalized Patients With Pulmonary TB and HIV Co-infection

This study has been completed.
Sponsor:
Collaborator:
Ontario Lung Association
Information provided by:
Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier:
NCT00414414
First received: December 19, 2006
Last updated: August 19, 2010
Last verified: August 2010
  Purpose

The purpose of this study is to determine if 30-day survival will be improved with addition of prednisone to standard tuberculosis (TB) therapy.


Condition Intervention Phase
Tuberculosis
HIV Infections
Drug: Prednisone
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Prospective Double Blind Placebo Control Clinical Trial of Prednisone as Adjunctive Therapy for the Treatment of Hospitalized Patients With Pulmonary TB and HIV Co-infection

Resource links provided by NLM:


Further study details as provided by Ottawa Hospital Research Institute:

Primary Outcome Measures:
  • Our primary objective is to determine if 30-day survival will be improved with addition of prednisone to quadruple standard TB therapy. We will measure all cause mortality at 30 days. [ Time Frame: 30 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Our secondary endpoints will involve the measurement of clinical, laboratory and radiological parameters and adverse reactions. [ Time Frame: 30 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 412
Study Start Date: February 2007
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: prednisone Drug: Prednisone
Other Name: non applicable
Placebo Comparator: placebo Drug: placebo
placebo
Other Name: non applicable

Detailed Description:

Tuberculosis (TB) is the leading cause of death in people infected with HIV worldwide. South Africa has one of the highest rates of tuberculosis and HIV in sub Saharan Africa and the world. Infection with HIV can result in activation of the latent form of TB to its active form. In places like sub Saharan Africa where the HIV rates are very high TB has spread with incredible vigor. In order to study this phenomenon, we conducted a preliminary project, which demonstrated that there are approximately 250 patients with active TB admitted to one urban South African hospital in one month and that almost half of them are infected with HIV. One quarter of them died while in hospital. They were young people with an average of 32 years. We are interested in undertaking clinical trials that will study novel therapies that can be added to the existing antimicrobial regimens in order to reduce the number of people dying from TB. One of these therapies would be the addition of prednisone, an oral steroid, to the standard TB treatment regimen. Steroids have been shown to be useful in TB meningitis and pericarditis in HIV positive and negative patients. However, steroids have never been tested in a formal manner in HIV patients with pulmonary TB. We have chosen to do our research in South Africa since the numbers of patients needed to design a clinical trial such as the one presented can only be found in such an environment. Prednisone is cheap, easily obtainable and thus a sustainable intervention in developing countries. The impact of the research would affect not only the international community including Canada but would certainly have a lasting sustainable effect on the local community in Pietermaritzburg, South Africa in addition to the rest of the world.

  Eligibility

Ages Eligible for Study:   17 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Newly diagnosed AFB smear positive pulmonary TB (via microscopy)
  • must be on quadruple standard chemotherapy for TB
  • patients admitted to the medical ward (Edendale Hospital (EDH)- Pietermaritzburg,KwaZulu Natal, South Africa)
  • must survive the first 24 hours after admission. In addition it takes up to 24 hours for the lab to assess all of the sputum samples sent for analysis
  • patients must live in Pietermaritzburg in order to ensure efficient follow up
  • positive HIV test (new or documented serodiagnosis via HIV antibody testing (ELISA Bio-rad ACCESS HIV 1/2 Immunoassay System))*
  • adults >17 yrs of age
  • consent to enter study * Only a screening test will be done to identify HIV positive patients, as the high prevalence of HIV in patients with pulmonary TB (60%) results in a very high positive predictive value, and a Western blot would not be needed as a confirmatory test.

Exclusion Criteria:

  • TB meningitis *
  • TB pericarditis *
  • adrenal Insufficiency *
  • old tuberculosis (Treatment for > 1 month prior to admission, Treatment failure) or known MDR-TB
  • significant co-morbidities such as diabetes, uncontrolled HTN, peptic ulcer disease and renal disease and palliative conditions (untreatable cancer), or another infection
  • other serious HIV related diseases such as cryptococcal meningitis, and Non Hodgkin's Lymphoma
  • pregnancy
  • previously treated with corticosteroids in the last month prior to admission, (9) other pulmonary pathogens identified in sputum 10) allergy to co-trimoxazole) (refer to co-trimoxazole section) *Based on clinical evaluation these patients will be excluded because evidence exists for using steroids in these conditions.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00414414

Locations
Canada, Ontario
The Ottawa Hospital - General Campus
Ottawa, Ontario, Canada, K1H 8L6
South Africa
Erendale Hospital
Pietermaritzburg, KwaZulu Natal, South Africa
Sponsors and Collaborators
Ottawa Hospital Research Institute
Ontario Lung Association
Investigators
Study Chair: Gonzalo Alvarez, MD Ottawa Hospital Research Institute
  More Information

No publications provided

Responsible Party: Dr. Gonzalo Alvarez, Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier: NCT00414414     History of Changes
Other Study ID Numbers: 2006301-01H
Study First Received: December 19, 2006
Last Updated: August 19, 2010
Health Authority: South Africa: Medicines Control Council
Canada: Health Canada

Keywords provided by Ottawa Hospital Research Institute:
TB
Tuberculosis
HIV
Co-infection
Steroid
Prednisone
oral corticosteroids
TB Treatment
South Africa

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Tuberculosis
Tuberculosis, Pulmonary
Coinfection
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Infection
Parasitic Diseases
Prednisone
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on August 20, 2014