Shortened MDR-TB Regimens:

Union-Supported Research

I.D. Rusen, MD MSc, The Union

June 21, 2016
CNS Webinar for Journalists

Outline
MDR-TB burden and shortcomings of current treatment
Union involvement in shortened MDR-TB regimens
Bangladesh MDR-TB treatment pilot project
West Africa observational study
STREAM clinical trial
Other treatment-shortening research
Conclusions

MDR-TB burden
and treatment limitations
Outline
WHO estimates* approximately 480,000 new MDR-TB cases
globally in 2014
Only a quarter of these estimated cases are detected and
treated
Of reported MDR-TB patients treated only 50% are treated
successfully
Currently recommended treatments are lengthy and often
difficult to tolerate
* World Health Organizations Global Tuberculosis Report 2015

Union Involvement in Shortened

Outline
MDR-TB Regimens

Union believed/believes strongly that a more accessible

and tolerable treatment for MDR-TB was/is urgently
needed
Experience from a Damien Foundation pilot programme
utilizing a nine-month treatment regimen in Bangladesh
demonstrated impressive results

Bangladesh Regimen
Daily treatment for 9 months
Months**
Drug
Kanamycin*
Isoniazid (H)
Prothionamide
Clofazimine
Gatifloxacin
Ethambutol
Pyrazinamide

1-4
1-4
1-4
1-9
1-9
1-9
1-9

* Kanamycin 3 times/week in month 4

** The intensive phase can be extended to 6 months

Results from Bangladesh Project

Published cohort (206 pts)
Cure

82.5%

Updated total (515 pts)

82.1%

Completion

5.3%

2.3%

Default

5.8%

7.8%

Death
Failure
Relapse

5.3%

5.6%

0.5%

1.4%

0.5%

Overall success rate:

87.9%
Am J Respir Crit Care Med 2010

0.8%
Overall success rate:
84.5%
Int J Tuberc Lung Dis 2014

Further Evaluation of Shortened Regimens:

Outline
A Parallel Approach
Additional cohorts
West Africa
Other countries

Randomised trial
STREAM Trial

Further Evaluation of Shortened Regimens:

Outline
A Parallel Approach
Additional cohorts
West Africa
Other countries

Randomised trial
STREAM Trial

West African
Outline
Cohort Study
Observational cohort study of 1000 patients on a modified
Bangladesh regimen
Nine countries of francophone Africa are participating :
Benin, Burkina Faso, Burundi, Cameroon, Central African
Republic, Cte d'Ivoire, DR Congo, Niger, Rwanda
Interim analysis of 408 patients demonstrated 82.1%
treatment success*
*Kuaban et al. Late breaker session. 46 th Union World Conference on Lung Health, Cape Town.

Further Evaluation of Shortened Regimens:

Outline
A Parallel Approach
Additional cohorts
West Africa
Other countries

Randomised trial
STREAM Trial

STREAM
Outline
Trial Design

STREAM is a randomised controlled trial of noninferiority design

In STREAM Stage 1 the Bangladesh regimen is

compared to the locally used WHO recommended
regimen in the participating countries

STREAM Stage 1 Trial Sites

Ethiopia (Addis
Ababa)

Mongolia (Ulan Bataar)

Vietnam
(Ho Chi Minh)
South Africa (Sizwe, Durban,
Pietermaritzburg)

STREAM Stage 1 Timelines

Actual

Planned

First patient randomised: 27th July 2012

Enrolled

424

400

Completion of recruitment:

July 2015

Final patient follow-up visit:

Q4 2017

Results expected:

Q1 2018

STREAM Stage 2
After extensive discussions between the study team, the
local investigators and other experts it was agreed that
additional regimens to be evaluated of primary interest to
patients and programmes would be:
a fully oral 9-month regimen
a 6-month simplified regimen
Both of these regimens include bedaquiline as part of a
broader agreement for support with Janssen
Pharmaceuticals

STREAM Stage 2 Timelines

Actual
First patient enrolled:
Enrolled

Planned

March 2016
10

1155

Completion of recruitment:

Q3 2018

Final patient follow-up visit:

Q1 2021

Initial end point results

expected:

Q3 2020

Other MDR-TB Research

Numerous other clinical research studies planned or
underway visit www.resisttb.org

Conclusions

The Union supports further evaluation of shortened MDR-TB

regimens to find the optimal regimens for patients and
programmes
As new medicines become available their potential impact on
treatment shortening must be evaluated in programme settings
Capacity of programmes to evaluate regimens in both
observational and RCT studies must be strengthened

Acknowledgements

STREAM Trial Management Group, STREAM trial site staff

and patients
West Africa Observational Study staff and patients
Research funders: USAID, DFID/MRC, AFD, Janssen
Pharmaceuticals

irusen@theunion.org

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www.theunion.org