One of the main objectives of the "TREAT TB"
research grant is to conduct a clinical trial to look at relatively shorter and
more effective multidrug-resistant tuberculosis (MDR-TB) treatment than the
current regimen for MDR-TB.
"One of the colleagues had done a study in Bangladesh
which was just published few months back - that a shortened standardised
regimen of just nine months was effective in treating MDR-TB patients. One of
the challenges of treating MDR-TB is that it is a long and difficult treatment
regimen - so this was a big breakthrough. What we are trying to do in our
MDR-TB trial, which is called "STREAM" is to see whether the same results
trial can be replicated in four other countries. India is one of the countries
being considered but final countries will be selected at the end of November
2010" said Dr ID Rusen, Director, Department of Tuberculosis,
International Union Against Tuberculosis and Lung Disease (The Union).
TREAT TB is managed by The Union, a global leader in TB
control since 1920, and funded by the United States Agency for International
Development (USAID). In implementing TREAT TB, The Union is joined by core
technical partners including the Institute of Tropical Medicine (Belgium), the
Liverpool School of Tropical Medicine (U.K.), the National Tuberculosis
Institute (India), EnCompass LLC (U.S.), Rede-TB (Brazil), Stellenbosch
University/Desmond Tutu TB Centre (South Africa), McGill University (Canada),
Brigham & Women's Hospital/Harvard School of Public Health (U.S.), Medical
Research Council (U.K), Dignitas International (Canada) and WHO-EMRO.
"The Union as an organization
had a role in clinical trials for a number of years but pretty limited usually
one trial going on at a time, and in the past couple of the main trials were
looking at the 6 months of TB treatment versus 8 months of treatment. One of
the study was called Study A, which first showed that 6 months was a more
efficacious treatment and then we followed it up with another trial that looked
at fixed dose combinations of treatment showing that it is more effective and
more convenient than a bunch of loose tablets. Those were the main trials we
have been involved. More recently we have been awarded a grant from USAID
called TREAT TB, it is a research grant" further explained Dr ID Rusen.
TREAT TB initiative aims to address the gaps in the current
research of new diagnostic tools in order to inform and improve the national
and global policies and practices. Two types of tools are assessed:
1) those that have already been scientifically evaluated and
adopted as a part of WHO policy and guidelines and
2) those promising tools for which final technical
deliberations and policy decisions at the global level have not yet been
reached. The goal of TREAT TB is to identify the remaining gaps in evidence and
associated opportunities to contribute to international efforts supporting the
successful implementation of new diagnostics.
study they had followed 200 patients on the standardised regimen. We are going
to do this in a more systematic clinical trial format in TreatTB initiative to
be as confident of the results that were first published of the Bangladesh
study" said Dr Rusen.
"Cure rate was over 80% in Bangladesh
among MDR-TB patients without relapses using the shortened regimen of nine
months. The current MDR-TB treatment is shortest at 18 months and often runs up
to 24 months or longer, and reported success rates globally are not close to
80%. So the fact that the treatment success rates were so high in Bangladesh
study, the regimen seems to be more tolerable to patients partly because of a
more shortened regimen, so the authors in the study published were quite
optimistic of the results" said Dr Rusen.
Talking about diagnostics and the methods used in Bangladesh
and proposed to be used in the TREAT TB study, Dr Rusen said: "So what
they did in Bangladesh and what we are trying to do in this study is to use
molecular test for early diagnosis of resistance to rifampicin and by extension
of MDR-TB, and that would be required to put the people on the regimen. Then
drug-susceptibility tests (DST) would further confirm. In this study, the
samples would be sent to a laboratory in Belgium
to test for anti-TB resistance and to make sure that the results are accurate.
Actual diagnosis and initial start of the treatment (as per study protocol)
would be based on a simpler molecular test done on-site."
Remarkably, Dr Rusen underlines the critical importance of
community engagement and support in conducting these studies and much higher
treatment success rates. "In Bangladesh,
there was a heavy emphasis on patients' support to make sure that the MDR-TB
patients have all the support they need, treatment was given as conveniently as
possible and with shorter time period people were more encouraged to adhere to
the treatment" said Dr Rusen.
There was a combination of factors that could have ensured
higher treatment success rate in Bangladesh.
Like some of the more difficult treatment that is part of the standard regimen
were given for shorter duration thereby making the regimen more tolerable to
"What we hope to do in this study itself is to
replicate that patients' support. It may be different in each country on how it
is done in order to ensure what is needed in the community or by the patient is
done" said Dr Rusen.
Speaking on whether this TREAT TB study or the earlier Bangladesh
study had looked into whether this regimen is also effective in people
co-infected with TB and HIV, Dr ID Rusen said: "One of the unknown aspects
is whether this regimen will work in patients co-infected with TB and HIV. Bangladesh
study doesn't answer this question. So the intention of the study is to have at
least one country that can address TB-HIV co-infection issue. We are right now
exploring the countries but we will have at least one country that can answer
the question whether this regimen will work in people co-infected with TB and
"The number of people with MDR-TB is estimated to be
450,000-500,000 and some estimates suggest that fewer than 10% get treated.
Such a small number of MDR-TB patients are actually being treated and part of
the reason is that it is such a difficult lengthy treatment. So to increase
access to MDR-TB treatment, it is important that we also find treatment that
can be as accessible and as effective as first-line treatment. It is very
important to show that such a relatively simpler regimen much shorter in
duration than current regimen can be more effective and successful in MDR-TB
patients. Also more the number of MDR-TB patients who are treated, and the
earlier they are treated, less will be the ongoing transmission of MDR-TB in
the community" said Dr Rusen while outlining the potential public health
outcomes of this important research.
"From the public health point of view, and global TB
control point of view, it is an important study. Again we also think it is important
because despite promising results in Bangladesh
and before those results are used more widespread, it is vital that the results
are replicated in a more objective way in a properly conducted trial such as
this" said Dr Rusen.
One of the areas Critical Path to TB Regimens (CPTR) is
addressing as others is preparation of sites for conducting research on TB
drugs or clinical trials. I would just emphasize how important that is, and as
we go about in this clinical trial, we are currently in countries trying to
assess sites. It gets so essential that there are sites available that can
conduct a well-done high-quality research to give the answers that are
necessary for programmes" explained Dr ID Rusen.
The Open Forum 4 on key issues in tuberculosis (TB) drug
development was recently held in Addis Ababa, Ethiopia
(18-19 August 2010). It was organized by Global Alliance for TB Drug
Development (TB Alliance), the Bill & Melinda Gates Foundation, the Stop TB
Partnership Working Group on New Drugs, and Treatment Action Group (TAG). This
Open Forum 4, raised and addressed key issues in TB drug development, with a
special focus on regulatory affairs.
Contributed by: Bobby Ramakant