There are about 3550 clinical studies being (or have been) conducted in South Africa. The country of the clinical trial is determined by the location of where the clinical research is being studied. Most studies are often held in multiple locations & countries.
In our formative research, analysis of antiretroviral treatment (ART) data manually entered in the Three Interlinked Electronic Registers (TIER.Net) showed poor viral load monitoring (VLM) and inadequate management of virological failure in HIV-positive patients on ART in rural KwaZulu-Natal, South Africa. ART interruption was high, with nearly half of patients falling out of care within 5 years of starting ART. Non-Nucleoside reverse transcriptase pre-treatment drug resistance exceeds 10% in the setting; the threshold required to trigger in a change in first-line ART using the public health approach. These factors are contributory to increasing HIV drug resistance (HIVDR) in this setting. HIVDR is associated with increased morbidity and mortality with the risk of transmitting drug-resistant HIV to sexual partners. The investigators presented these findings to healthcare providers, policy makers and community representatives with brainstorming of health system challenges and potential interventions. This study aims to complement these findings by investigating the clinical and process impediments in VLM within the health system and to develop a quality improvement package (QIP) to address the gaps. The stakeholders recommended such QIP would utilise the viral load (VL) champion model, a named healthcare provider who would be the focal point for ensuring proper administrative management of viral load tests and results through identification of those who need tests and triaging of results for action. This QIP will be supported by technological enhancement of the routine clinic-based TIER.Net software which will allow daily automatic import of results from the National Health Service Laboratory (NHLS) to TIER.Net and development of a dashboard system to support VLM. In addition, results of contact tracing will be recorded and followed up pro-actively if not initially successful. The investigators will evaluate the effectiveness of these interventions compared to standard care for improving VLM and virological suppression using an innovative effectiveness-implementation hybrid cluster-randomised design in 10 clinics. A within-trial health economics analysis will be undertaken using recommended methods to examine the cost-effectiveness of the intervention compared to standard care.
Resistance to anti-tuberculosis drugs is a continually growing problem. Multidrug-resistant tuberculosis (MDRTB) is resistance to at least rifampicin and isoniazid, and extensively drug-resistant TB is additional resistance to a fluoroquinolone and a second injectable line drug. Methods currently employed in testing for resistance are inadequate and a contributing factor to the 40-50% MDR-TB treatment success rate. Current drug susceptibility testing methods are slow for most drugs, taking weeks. Rapid molecular methods such as the line probe assays, e.g. Hain GenoType MDRTBplus and sl, provide resistant calls to only a limited number of drugs, and are often less useful in smear negative patients. Molecular technologies such as sequencing can provide a comprehensive readout of drug resistance and are able to detect resistant populations at very low levels (≤1%), thus enabling individualized therapy. This can be done directly from sputum. Targeted sequencing amplifies regions of genomic DNA associated with resistance prior to sequencing. Rapid analytic software is used to process the raw sequence data, identify resistance causing mutations and provide a readout of clinically relevant information. However, the feasibility, and more importantly the impact, of this approach has not been evaluated in a clinical trial to establish proof of concept. Aim 1: To conduct a randomised controlled trial to determine the impact of sputum-based targeted sequencing in detecting resistance to second-line TB drugs compared to the current programmatic standard of care (Hain MDRTBplus/sl and adjunct phenotypic drug susceptibility testing) when used to inform of treatment for MDR-TB. Aim 2: To compare currently available drug resistant sequencing pipelines for diagnostic accuracy, sensitivity, specificity and predictive value as compared to culture based phenotypic drug susceptibility testing. Aim 3: To compare the feasibility, accuracy, turn-aroundtime, and cost implications of the above-mentioned diagnostic approaches.
Randomised controlled trial to investigate the efficacy of adding metronidazole pre-operatively to kefazolin in reducing postpartum infection
The Human Immunodeficiency Virus (HIV) has been recently linked to increased risk for cardiovascular diseases (CVDs). The prevalence of cardiovascular diseases and its risk factor, hypertension, are very high in African communities especially in the working age group which also happens to have the bulk of young female adults in the reproductive age. Hypertension in African children is becoming a real cause for concern though its etiology remains elusive. Thanks to antiretroviral therapy (ART) use, many more infected persons live long enough to reproduce, consequently, an increasing number of children are being born to mothers who are infected with HIV. Could it be that in utero exposure of these children to HIV/ART contribute in programming them for increased risk for cardiovascular diseases thus making them more vulnerable to hypertension in childhood and adulthood? This study is aimed at exploring the possible association of in utero exposure to the HIV/ART environment and an increased risk for cardiovascular disease.
This is a phase I/IIa, open label, multicenter interventional study of Gallium-68 radiolabeled PEG-αvβ3-Integrin Adhesion Complex antagonist conjugate (Ga-68-PEG-Αvβ3-IAC) Positron Emission Tomography (PET/CT) imaging, intended for diagnosis, and clinical management of patients with angiogenic breast cancer.
This study is a Phase I/II clinical evaluation of a new investigational agent, Lutetium-177-DOTAGA-IAC (HurlutinTM Lu-177) to treat patients with unresectable angiogenic breast cancer who have previously been treated with at least one prior line of therapy.
UPRIGHT-HTM will compare risk stratification, treatment efficiency and health economic outcomes of a diagnostic approach based on home blood pressure telemonitoring combined with urinary proteomic profiling with home blood pressure telemonitoring alone
human immunodeficiency virus / acquired immunodeficiency syndrome (HIV/AIDS) is the second leading cause of death in Africa. Adolescents living with HIV (ALWH) are at increased risk for HIV-related morbidity and mortality due to poor retention in HIV care and suboptimal antiretroviral therapy (ART) adherence. Despite having the world's largest population of Adolescents living with HIV (ALWH) (15-24 years, n=870,000), only 14% of South African ALWH are on ART, 12% are retained in HIV care 1-2 years after ART initiation, and 10% are virally suppressed. During treatment interruption, the effects of ART quickly reverse, increasing transmission risk, treatment resistance, and potentially fatal complications. Unless their treatment retention and adherence improves, ALWH will continue to transmit the virus to their sexual partners and die prematurely. While social support is often viewed as a bridge that joins ALWH to key resources within their environments, little is known about which types of social support are most impactful and from whom within their network, particularly among ALWH in endemic countries. Moreover, many South African ALWH lack social support from key social network members due to lack of HIV status disclosure, increasing their risk for poorer HIV-related outcomes when compare to their disclosed peers. Social network interventions (i.e., those that leverage the resources within one's network to improve behaviors and outcomes) that meet the needs of both ALWH who are disclosed and non-disclosed are needed, but lacking. Such inventions have the potential to facilitate appraisal support, during which ALWH receive targeted assistance with identifying appropriate and trustworthy people in their lives. More broadly, there exists a lack empirically supported interventions aimed at improving retention in HIV care and ART adherence for ALWH in low-middle income countries. This proposal follows the multiphase optimization strategy (MOST), a comprehensive framework for optimizing and evaluating multicomponent behavioral interventions.
A randomised, double-blind, cross-over study to assess the analgesic effect of methoxyflurane at moderate high altitudes in a wilderness field setting. Phase IV, randomised, double-blind, cross-over clinical trial to evaluate the analgesic effect of methoxyflurane at moderate high altitudes in a wilderness field setting, in 24 healthy volunteers
The purpose of the study is to prospectively assess the use of a modified tracheal balloon dilator in children (<13 years old) with subglottic or tracheal stenosis. The hypothesis is that the device will effectively dilate the stenotic segment, whilst maintaining oxygenation (if applicable). The primary aim is to measure the stenosis prior to, and after dilatation; using diameter and the modified Myer-Cotton grading system. Secondary aims include assessment of stenosis at six-week follow-up and monitoring arterial oxygenation nadir (using peripheral plethysmography) during the procedure.