STREAM CLINICAL TRIALS

Map of Trial Sites

The map above shows the sites that have participated in Stage 1 of the STREAM Trial. Several sites are currently under consideration for Stage 2.


Mongolia


Background:
As one of seven countries in the WHO Western Pacific Region with high TB burden, Mongolia has been selected as one of the STREAM trial sites. According to WHO estimates, prevalence was 227 per 100 000 population and mortality rate was 2.27 per 100 000 population in 2014 in Mongolia. In 2014, 4,771 TB cases were reported (4,483 new and relaped cases; 288 previously treated, excluding relapses). In the same year, MDR-TB treatment in was initiated in 294 patients. One third of sputum smear-positive TB patients whose treatment had failed was diagnosed with MDR-TB (2010 or 2011) in Ulaanbaatar, Mongolia’s capital.

Stage 1:
The National Centre for Communicable Diseases (NCCD), located Ulaanbaatar, the capital of Mongolia, is the main Mongolian partner for the STREAM trial. This agency is devoted to administer and manage the control, prevention, surveillance, diagnosis, and treatment of communicable diseases. One of their central goals is to reduce the spread of TB and TB-related deaths. A total of 33 patients were enrolled in STREAM Stage 1 in Mongolia from 3 September 2014 to 8 June 2015. The local clinical team is monitoring the STREAM patients and will continue patient follow-up until Stage 1 is completed in late 2017.

Stage 2:
Given the successful implementation of Stage 1 in Mongolia the site was an excellent candidate to continue into the second stage of the trial. Mongolia was the first country to recruit patients into STREAM Stage 2 and began recruitment on 28 March 2016. NCCD is expected to recruit 100 patients into STREAM Stage 2 by 2018.

Ethopia

Background:
Ethiopia is one of the 22 highest TB burdened countries in the world, according to the WHO. In 2014, estimated prevalence and incidence were 200 and 207 per 100 000 population, respectively, and mortality rate was 38.7 per 100 000 population. In 2014, 119 592 new TB cases were notified. It is also estimated that 1.6% of the new TB cases were MDR-TB and 12% of those undergoing retreatment have developed MDR-TB; MDR-TB treatment in was initiated in 557 patients in 2014.

Stage 1:
For STREAM Stage 1, a total of 126 patients were enrolled in the STREAM trial at two sites in Addis Ababa, Ethiopia. A total of 55 patients were randomized from 19 February 2013 to 8 June 2015 at the Armauer Hansen Research Institute (AHRI) and 71 patients were recruited between 29 November 2012 and 12 June 2015 at St. Peter’s Hospital. The local clinical team is monitoring the STREAM patients and will continue patient follow-up until Stage 1 is completed in late 2017. The Armauer Hansen Research Institute was established by the Norwegian and Swedish Save the Children organizations seconded by the Ministry of Health in Ethiopia in 1970. They were built as a biomedical research institute next to the All Africa Leprosy Rehabilitation and Training Hospital and joined the ministry of Health in 2003. They are dedicated to better understand tuberculosis and leprosy through basic biomedical research. AHRI seeks to develop evaluation and build the capacity for new methods for TB prevention, treatment, and control in the Horn of Africa. The St. Peter’s TB Specialized Hospital is part of the Ministry of Health of the Federal Democratic Republic of Ethiopia and was established in 1953. Their mission is to become center of excellence and model TB general specialized Hospital in East Africa. Its objectives are to integrate internal medicinal pediatrics services; give practical training on laboratory and nursing; and to improve research, training, and health services. St. Peter’s offers a host of services including laboratory, TB testing, voluntary counselling and testing, health-facility based medical care, psycho-social support, information, education and communication, as well as HIV/AIDS research.

Stage 2:
Given the successful implementation of Stage 1 in Ethiopia, the sites were chosen to continue into the second stage of the trial and Gondar University Hospital was selected as a third trial site. Ethiopia is the second country to initiate STREAM Stage 2 and has begun recruitment in June 2016 . The three sites are expected to recruit a total of 130 patients into STREAM Stage 2 by 2018. The Gondar University Hospital (GUH) is a 400 bed university hospital, which acts as the referral centre for four district hospitals in the area. It has a range of specialities including pediatrics, surgery, gynecology, psychiatry, HIV care and an outpatient’s clinic. Within its 400 staff it employs 50 doctors, 150 nursing staff, three pharmacists, 90 care staff and 25 laboratory scientists. The staff serves a population of four million across the region. In April 2010, GUH opened a renovated TB treatment ward which was funded by the President’s Emergency Plan for AIDS Relief (PEPFAR).

South Africa

Background:
The South African TB epidemic is largely driven by a high HIV prevalence. There is evidence of decrease in Drug Sensitive TB in South Africa due to large scale rollout of antiretroviral treatment. However, MDR TB incidence continues to climb. In 2014, 318 193 new TB cases were notified. It is also estimated that 1.8% of the new TB cases were MDR-TB and 6.7% of those undergoing retreatment have developed MDR-TB; MDR-TB treatment in was initiated in 11 538 patients in 2014.

Stage 1:
Kwazulu Natal Province is the hotspot of Drug Resistant TB and was where the first documented outbreak of XDR-TB occurred. King DiniZulu hospital is located in Durban and at the time of the start of STREAM 1 was the referral site for all MDR-TB cases in the province. This hospital with over 1200 beds offers both TB and psychiatric services. A research unit was established in 2007 by the South African Medical Research Council (SAMRC) to conduct the registrational trials for bedaquiline. The site then went on to be a STREAM 1 site and has undergone changes in management from the SAMRC to THINK and then finally to Wits Health consortium. For STREAM Stage 1, a total of 165 patients were enrolled from three sites in South Africa. In total, 90 patients were enrolled in the STREAM trial at King DiniZulu Hospital Complex in Durban from July 2012 through February 2015. The mission of Doris Goodwin Hospital, located in Pietermaritzburg, also in KwaZulu Natal, is to be a center of excellence in providing high quality medical services for managing MDR-TB as well as specialized, sub-acute, and recurring TB. This hospital which serves patients with 100 beds was operated by an NGO, Santa for TB Management. It was then taken over by the government and later became specialized in MDR-TB management. A research site was established by THINK to conduct STREAM Stage 1. At the Doris Goodwin Hospital in Pietermaritzburg, 14 patients were recruited between 20 November 2014 and 30 June 2015. The Sizwe Tropical Disease Hospital is the referral hospital for patients within Gauteng Province, the most populous province in South Africa. Formally a fevers hospital, the location of the facility is ideal for admission and treatment of infectious MDR- and XDR-TB patients. In 2008, a clinical trial facility was established on the premises by Wits Health Consortium. Following the successful implementation of the registrational trials for bedaquiline, STREAM 1 begun enrollment in August 2012. A total of 61 patients were enrolled from 28 August 2012 to 19 June 2015 at the Sizwe Hospital in Johannesburg. The local clinical teams continue to monitor the STREAM 1 patients and will continue patient follow-up until Stage 1 is completed in late 2017.

Stage 2:
Given the successful implementation of Stage 1 in South Africa, the sites were chosen to continue into the second stage of the trial. South Africa will be the third country to initiate STREAM Stage 2 and will begin recruitment in June 2016. The three sites are expected to recruit a total of 150 patients into STREAM Stage 2 by 2018.

Vietnam

Background:
In 2015, WHO reported Vietnam to be among the 22 tuberculosis high-burden countries in the world. Vietnam has been selected as one of the STREAM trial sites. According to WHO estimates, prevalence was 198 per 100 000 population and mortality rate was 20 per 100 000 population in 2014 in Vietnam. In 2014, 102 087 TB cases were reported. In the same year, MDR-TB treatment in was initiated in 1 532 patients.

Stage 1:
Pham Ngoc Thach University of Medicine, located in Ho Chi Minh City, the capital of Vietnam, is the main partner for the STREAM trial in Vietnam. This medical university was established in 1989 and is a multi-disciplinary school that is responsible for training health care providers in order to improve the health of Ho Chi Minh City. It is also one of the key training and medical research facilities in the southern part of Vietnam. A total of 100 patients were enrolled in STREAM Stage 1 in Vietnam from 22 November 2012 to 26 March 2015. The local clinical team is monitoring the STREAM patients and will continue patient follow-up until Stage 1 is completed in late 2017.