A new PNG arm of a multi-country randomised control trial of a new Tuberculosis Point-of-Care technology will be run by Papua New Guinea (PNG) Central Public Health Laboratory, in partnership with the PNG Institute for Medical Research (PNGIMR) and Burnet Institute.

Together with six other countries, the group plans to evaluate the impact of GeneXpert Omni, in comparison with current tests. Outcomes of interest include; time to diagnosis and treatment, yield over smear microscopy, mortality, and feasibility/acceptability. Funding for the study is provided by FIND (Foundation for Innovative New Diagnostics). Rapid and accurate diagnosis of TB will be fundamental to achieving the ambitious targets set by the World Health Organization’s (WHO) new END TB strategy. In this regard, the Xpert MTB/RIF Assay (‘Xpert MTB/RIF’) on the GeneXpert platform has had a significant impact, and is now in use in over 100 countries.

While Xpert MTB/RIF introduction has produced results including increased detection of drug resistant TB and bacteriologically positive case notifications, the assay is limited in its ability to replace smear microscopy, as it has requirements including a stable electricity supply and temperature control, often unavailable at the microscopy centre level. In addition, the assay has a pooled sensitivity of 88 percent which reduces to as low as 50 percent for patients with paucibacillary TB, such as children.

In response to the limitations of Xpert MTB/RIF and the GeneXpert platform, Cepheid, Rutgers University and FIND collaborated to develop the Xpert MTB/RIF Ultra (‘Xpert Ultra’) test to increase the sensitivity for TB detection to be similar to that of culture, in addition to improving the accuracy of rifampicin detection.

Additionally, the point-of-care GeneXpert Omni (‘GeneXpert Omni’) has been developed. Unlike the GeneXpert platform, the Omni is battery operated and is able to withstand significant temperature variations and environmental conditions, enabling it to be used at the point-of-care in microscopy centre level facilities. Use of Xpert Ultra on GeneXpert Omni (hereafter described as ‘Omni/Ultra’) will allow the rapid diagnosis of TB and DR-TB, allowing patients to be promptly initiated on effective treatment.

This has the potential to improve patient outcomes and, ultimately, reduce TB transmission. The rapid uptake of such new tools in the highest burden countries, where health systems are often under strain, is essential.

PNG has been selected to participate in a multi-country randomised control trial of the new technology. Together with six other countries, we hope to evaluate impact including:

• time to diagnosis and treatment,
• yield over smear microscopy,
• mortality, and feasibility/acceptability.

Objectives:

1. To compare the proportion of bacteriologically confirmed pulmonary TB patients who initiate TB treatment within 60 days of enrolment, between the intervention group (Omni/Ultra + same day treatment initiation) and the control group (standard diagnostic algorithm + standard treatment initiation).

2. To compare the diagnostic yield of Omni/Ultra with that of sputum smear microscopy.

Activities:

The design includes an initial period in which no clusters are exposed to the intervention. Subsequently, at regular intervals (the “steps”) one cluster (in this case, equalling one facility) is randomised to cross from the control to the intervention This process continues until all clusters have crossed over to be exposed to the intervention. At the end of the study there will be a period when all clusters are exposed to the intervention. Data collection continues throughout the study, so that each cluster contributes observations under both control and intervention observation periods. Within an ethical research framework, this will enable prospective comparisons of intervention and control within (before and after the intervention introduction) and between sites (with and without intervention).

Within this design:

• All facilities will receive the intervention by the end of the study. The order in which the three facilities receive the intervention is determined at random. - Randomisation will be carried out using a computer program implemented by a Burnet Institute-based biostatistician.
• Randomisation and subsequent determination of the randomisation order will be carried out before the commencement of the study.
• Sites will be informed one month before the beginning of their transition phase.
• It is expected that an average of three presumptive cases per day will be enrolled per site for a total of six months (120 days of enrolment), with a one month training and transition period.
• Training on the study procedures and data collection tools will be held for all sites during the relevant month long transition period at each site. During this time, no enrolments will be made.

In total, approximately 864 presumptive pulmonary cases are expected to be enrolled, with nine cumulative months allocated to the intervention (i.e. approximately 432 presumptive cases), and nine cumulative months allocated to the control (approximately 432 presumptive cases). This figure takes into account a 20 percent non-enrolment rate.

Timeline

July 2016 - December 2019

Outcomes

The study will have significant potential benefits to patients and communities. Utilization of this new, accurate test as a replacement for sputum smear microscopy for the detection of TB and DR-TB has the potential to reduce the time that people must wait to receive their results and get started on treatment, increase the accuracy of TB diagnosis and reduce the number of people lost through the diagnostic process, and therefore reduce mortality and morbidity. Additionally reducing the time to treatment initiation has public health benefits in terms of breaking the chain of TB transmission.

As part of a multinational study, this study will significantly shape global policy related to Omni/Ultra roll out, and will provide valuable guidance regarding the operational and acceptability aspects of introducing the test in practice.