STREAM CLINICAL TRIAL

Map of Trial Sites

The map above shows the sites that are active in Stage 1 and Stage 2 of the STREAM Trial. Additional sites will be joining the trial shortly.


Ethiopia

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 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 Tuberculosis Specialized Hospital (St. Peter's). The local clinical team is monitoring the STREAM patients and will continue patient follow-up until Stage 1 is completed in 2018.

The AHRI 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.

St. Peter’s was established in 1953 as part of the Ministry of Health of the Federal Democratic Republic of Ethiopia. Their mission is to become the center of excellence and a model TB 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 same sites were chosen to continue into the second stage of the trial. Ethiopia is the second country to initiate STREAM Stage 2 and began to recruit patients in June 2016. The two sites are expected to recruit a total of 130 patients for the trial.

Georgia

Background:
Tuberculosis remains a major public health challenge in Georgia. In 2015, an estimated 12% of all new TB cases and 33% of retreatment cases had MDR/RR-TB. In the same year, the estimated incidence of MDR/RR-TB was 25 per 100 000 individuals and, among the TB cases notified during the year, 550 were MDR/RR-TB cases. Georgia’s Five Year TB Control objectives are to: decrease death, disease, and infection rates, and prevent the development of drug-resistant TB.

Stage 2:
Given the significant MDR-TB burden in Georgia, the National Center for Tuberculosis and Lung Diseases (NCTLD) in Tbilisi was selected to participate in Stage 2 of the trial. Georgia is the fifth country and the eighth site to initiate STREAM Stage 2. The NCTLD is currently expected to recruit as many as 75 patients by the end of 2018.

The NCTLD was founded in 2001 as a non-profit organization that combined the Institute of Tuberculosis and Lung Disease, Tbilisi’s TB Hospital, and the Georgian Railway TB-Stationary. The NCTLD designed and currently oversees implementation of the National Tuberculosis Program at health facilities throughout the country. It also provides TB prevention, diagnosis, and treatment.

India

Background:
India continues to have the highest TB burden in the world and is included in all three high-burden country lists for TB, TB/HIV, and MDR-TB.

In 2016, the estimated incidence of TB in India was approximately 2.8 million cases and nearly 500,000 people died. Although the prevalence of MDR-TB in India is considered low in terms of percentage of TB cases (~3% of new cases and ~12% of retreatment cases), this translates into large numbers of cases. With an annual incidence of approximately 150,000 rifampicin-resistant/MDR-TB cases, India accounted for nearly one-third of the estimated global MDR-TB burden in 2016.

Recently, the Government of India has produced a National Strategic Plan (2017–2025) that sets out activities and interventions that India will undertake to bring about significant change in the country’s incidence, prevalence, and mortality from TB. The goal is to achieve a “TB free India” by 2025.

Stage 2:
Two sites will be implementing STREAM Stage 2. The National Institute for Research in Tuberculosis (NIRT) under the Indian Council of Medical Research (ICMR) is an internationally recognized institution for TB research. It is also a Supranational Reference Laboratory for the South East Asia region and a WHO Collaborating Centre for TB Research and Training. NIRT, formerly known as the TB Chemotherapy Centre and then TB Research Centre, was established in Chennai (then Madras) in 1956 under the leadership of Dr. Wallace Fox from the UK Medical Research Council (formerly known as British Medical Research Council), and is acclaimed globally for conducting the first controlled clinical trial in TB, the “Madras Study”. As of November 2017, NIRT had undertaken nearly 35 randomized controlled clinical trials for treatment of both pulmonary and extra-pulmonary TB.

The BJMC Civil Hospital in Ahmedabad was established as The Civil Hospital in 1841 in the state of Gujarat. In 1953, the hospital was relocated to its current premises in Asarwa and renamed as the New Civil Hospital, which currently has 44 wards with more than 2000 beds and serves over 100,000 inpatients annually in addition to nearly one million outpatients. The hospital launched the first Revised National TB Control Programme in India in 1993 and the implemented the pioneer Programmatic Management of Drug-Resistant TB (PMDT) program in 2007. It is one of the largest hospitals in Asia and is also a teaching institute affiliated with BJ Medical College. The State TB Demonstration Centre that is housed in the BJMC Civil Hospital Campus was the first to receive accreditation as a state level Intermediate Reference Laboratory and first to be established as a national level training centre for PMDT in 2008. It was also the first state-level laboratory to receive accreditation to perform second line drug susceptibility testing in 2013.

Screening in India will start in December 2017. Together, the NIRT and BJMC sites are expected to recruit 300 patients by the end of the trial.

Moldova

Background:
The Republic of Moldova continues to suffer from high TB morbidity. The country is among the 18 priority countries for tuberculosis control in the WHO’s European Region and is one of 30 countries with a high burden of MDR-TB (MDR-TB). Moldova has the highest estimated of incidence of MDR- and rifampicin-resistant TB in the world at 96 per 100 000 population.

Stage 2:
The Institute of Phthisiopneumology “Chiril Draganiuc” (IPP) from Chisinau, Republic of Moldova was established in 1959. It is the main research institution and republican clinical structure in the field of tuberculosis control and nonspecific pulmonary diseases in Moldova. The IPP implements all activities of the National Tuberculosis Control Program and trains future clinicians and researchers. The Institute also conducts research in epidemiology, diagnosis, and treatment of tuberculosis and nonspecific pulmonary diseases. The facility operates a 410-bed hospital to treat TB and other pulmonary diseases; the ambulatory department receives 36,000 visits per year. The IPP also houses the National TB Reference Laboratory. Recruitment in Moldova began in June 2017. The site is expected to recruit up to 75 participants in STREAM 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 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 in Ulaanbaatar, is the main Mongolian partner for the STREAM trial. This agency is devoted to administering and managing 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 early 2018.

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.

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 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 Complex is located in Durban and at the time of the start of STREAM Stage 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. The site is managed by 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 Stage 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 early 2018.

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.

Uganda

Background:
Uganda is one of the WHO-designated high TB burden countries, with over 83,000 estimated TB cases in 2016. In the same year, the WHO estimated that 1.6% of new cases and 12% of previously treated cases were MDR/RR-TB cases, and nearly 500 laboratory-confirmed cases of MDR/RR-T were reported.

Stage 2:
STREAM Stage 2 is recruiting at one site in Kampala, Uganda, in partnership with the Makerere University Lung Institute and the Mulago National Referral Hospital.

The Lung Institute was established in the Makerere College of Health Sciences to specialize in fighting lung diseases such as tuberculosis. In addition, Makerere University has significant experience implementing clinical trials as part of initiatives including Drugs for Neglected Diseases Initiative.

The Mulago Hospital was founded in 1913 and is the main national regional hospital for the entire country and a teaching hospital for the Makerere College of Health Science. With over 1700 hospital beds, they seek to provide super-specialized healthcare, to provide training and to conduct operational research in line with Ministry of Health requirements. The Hospital’s capacity for conducting clinical trials, its high volume of patients, and its expertise in managing tuberculosis are factors that contributed to selecting this partner in Uganda.

The STREAM site in Uganda is expected to recruit 80 participants for STREAM Stage 2.

Vietnam

Background:
In 2015, WHO reported Vietnam to be among the 22 tuberculosis high-burden countries in the world. Due to its high TB burden, 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 and MDR-TB treatment 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 early 2018.