Clinical trials

A cluster randomized trial (CRT) of the novel sickle cell disease (SCD), M-health based SCD Information Management and Communication system SIMCS vs routine new born screening strategy in health care centres in Uganda to evaluate impact on access screening, coordination of care and clinical outcomes

This will be a randomized controlled trial of asymptomatic (Cryptococcal Antigen test)CrAg positive persons in Uganda. Patients will be randomized to receive preemptive treatment with 1 dose of liposomal amphotericin (10mg/kg) in addition to standard of care fluconazole therapy. How the enhanced antifungal therapy prevents progression to meningitis in the first 24-weeks and overall survival in those who receive the intervention compared with participants receiving fluconazole per World Health Organisation (WHO) and national standard of care therapy will be evaluated.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis-attributable mortality in sub-Saharan Africa (sSA) is high, with in-hospital mortality in some settings approaching 40%. Studies show that mortality among children under 5 years hospitalized with sepsis remains high within the first 6 months of discharge. Additionally, high mortality has been observed among other populations within sSA, with factors such as HIV infection being associated with increased risk. Reducing sepsis deaths contributes to the achievement of the Sustainable Development Goals (SDG), particularly SDG 3 in reducing maternal mortality (3.1), neonatal and under five mortality (3.2), and burden of mortality from communicable diseases (3.3) and improving universal health coverage (3.8). The World Health Organization (WHO) has recognized sepsis as a global priority, with low- and middle-income settings being particularly affected. In sSA, sepsis is commonly associated with infectious diseases like malaria, Human Immunodeficiency Virus/ Acquired Immunodeficiency Syndrome (HIV/AIDS), pneumonia, tuberculosis, and diarrhea. Guidelines from the Surviving Sepsis Campaign (SSC) have become standard in some settings. However, little is known about patients' status post-discharge. This study aims to evaluate two post-discharge follow-up strategies for adult sepsis patients. Study duration is 45 months, participants will receive intervention up to 90 days post discharge. Description of intervention: Post-discharge follow-up strategy 1: Enhanced Discharge Intervention (EDI) Post-discharge follow-up strategy 2: EDI plus Interactive Voice Response (IVR) Objectives: The study aims to evaluate two post-discharge follow-up strategies for adult patients hospitalized with sepsis, focusing on their efficacy in reducing the 90-day mortality, and their effect on return to follow-up, number of re-admissions, and quality of life. Primary efficacy endpoint * 90- day all-cause mortality post discharge Secondary end points * Time to death * 28-day all-cause mortality * Attendance within 14-day check-up post discharge * Re-admission within 28 and 90 days * Days alive and out of hospital (DAOH) * Quality of life score (Baseline vs 28 day and Baseline vs 90 days) * Differences in baseline demographic and clinical characteristics (e.g., age, sex, disease severity, comorbidities, key laboratory values) between randomized participants and screen failures. Study design: This is an open-label, randomized, parallel, interventional study, with two post-discharge follow-up strategies: 1) EDI; or 2) EDI plus IVR system. Fixed allocation randomization at a 1:1 ratio will be applied to either study arm. Sample size: A total of 1,410 (705 per arm) from the four countries (Uganda, Nigeria, Ghana and Mozambique) will be enrolled competitively across the sites.

The goal of this clinical trial is to learn if the intervention of delivery of antiretroviral drugs by medical drones can improve virological suppression in a fisherfolk community population living with HIV in the islands of Kalangala District, Uganda. The main question it aims to answer is: Can delivery of anti-retroviral therapy (ART) by unmanned aerial vehicles (medical drones) to people living with HIV (PLHIV) improve virological outcomes compared to the standard of care (SOC) in an underserved population? Primary hypothesis: The investigators hypothesize that using drones will increase viral suppression in those receiving the intervention as compared to the control or outcome measure one-will be the proportion of PLHIV with undetectable HIV viral load in the intervention (drones) versus SOC arm at 12 months. If there is a comparison group: Researchers will compare \[Medical Drones delivery group\] to see total cost of 12 months medication delivery to people living with HIV (PLHIV) in the intervention as compared to standard of care (SOC) arm. Proportion PLHIV with an undetectable viral load at 6, 18 and 24 months in intervention Rates of retention in care of PLHIV at 6,12, 18 and 24 months in intervention as compared to SOC arm * Participants will be seen every 6 months for 24 months * They will have blood draws for viral load tests * They will complete interviewer administered questionnaires * The intervention is last-mile delivery of ART by drones to landing sites

: Informed consent is an important aspect of research, however in psychiatry research it remains an ethical dilemma, for the lack of clarity on the consent process deters some researchers from mental health research, and yet a good research must ensure that this moral stand is undertaken. Studies that literally test measures that improve the informed consent process in participants with psychotic disorders have been scanty. To date, there is a noticeable absence of an evidence-based intervention for enhancing the comprehension of consent information in research participants with psychotic disorders in the Ugandan context. Thus, this research study is to explore methods like incorporating multimedia components, such as audio and visual aids, to enhance the participants' grasp of research particulars, thereby enabling them to make informed decisions effectively and give informed consent when they are invited to participate in research projects. Objective: To evaluate the comprehension of informed consent, identify key factors that that are associated with comprehension of consent, and determine the feasibility, acceptability, and preliminary effectiveness of audio-visual aids on enhancing the comprehension of consent information during the consenting process in research involving individuals with psychotic disorders. Methods: This will be a multi-method research design that will be achieved through four sub-studies. Sub-study 1 will be cross-sectional and will involve an assessment of comprehension of informed consent using the University of California Brief Assessment of Capacity to Consent (UBACC) tool. Participants will be patients aged 18- 60 years with a psychotic disorder. Sub-study 2 will be a qualitative study that utilizes a user-centered design approach by engaging a multidisciplinary team of stakeholders to develop a multimedia audio-visual consent tool. Sub-study 3 will be a randomized pilot study designed to evaluate the effectiveness of the multimedia video consent tool and how it compares with the traditional paper method in enhancing participants' comprehension of consent information. Sub-study 4 will be a mixed-methods approach using quantitative and qualitative data from exit interviews to assess the Feasibility and Acceptability of the audio-visual consent tool for individuals with psychotic disorders and the research assistants administering the tool in a mental health research setting

The goal of this clinical trial is to assess the efficacy(effectiveness) of doxycycline, a potent inhibitor of matrix metalloproteinase (lung collagenase) activity in prevention of Tuberculosis associated lung fibrosis and associated lung function decline among patients with drug sensitive advanced TB. The main question\[s\] it aims to answer are: * Does doxycycline have a significant anti-fibrosis role when given as adjuvant therapy to TB patients with advanced pulmonary TB in a double blind randomized placebo controlled trial? * How does long term respiratory function defer between patients who received adjuvant doxycycline aimed at prevention of TB associated lung fibrosis and those who received a placebo in a double blind randomized controlled trial? Participants will be subjected to the following: * Experimental arm: Doxycycline 100 mg once daily for 12 weeks administered concurrently with standard of care anti-TBs. * Comparator arm: Placebo once daily for 12 weeks administered concurrently with standard of care anti-TBs.

The goal of this observational study is to understand the approach to pain management before, during, and after surgery at Mulago National Referral Hospital. It is focussed on adult patients undergoing major surgery. The main questions it aims to answer are: * How often are combinations of pain medications utilised before, during and after surgery? * Do combinations of pain medications result in better pain control after surgery compared to single pain medications? Information on pain medications will be obtained from patient records. Patients will be asked to rate their pain after surgery every 6 hours for 24 hours.

Although over 75% of children with sickle cell disease (SCD) are born in sub-Sahara where the disease highly contributes to under-5 mortality and causes life-long debilitation, evidence-based strategies to control SCD are not widely implemented in this region. Early detection of SCD by universal infant screening is a pillar of SCD control. Despite the affordability and move to adopt point-of-care (POC) SCD screening assays in sub-Sahara Africa, the absence of screening information management and communication systems (SIMCS) impedes standardized, systematic, coordinated, nationwide SCD screening programs. The long-term goal of the proposed research is to develop a SCD SIMCS that will enable universal SCD screening in the sub-Sahara African setting. The objective is to test and optimize a custom SCD SIMCS app and digital network to facilitate SCD screening and then evaluate its impact on access to SCD screening and care and on clinical outcomes of children with SCD in Uganda. The central hypothesis is that the SCD SIMCS will facilitate accurate and coordinated POC SCD screening that is accessible at health centers in urban and rural Uganda. The rationale is to build a custom SCD SIMCS on existing nationwide digital and health infrastructure in Uganda to standardize use of affordable POC assays at health centers nationwide. The central hypothesis will be tested by pursuing two specific aims: 1) Develop and evaluate a four-module ≥3G cell phone app for a novel SCD SIMCS (R21 Phase); 2) Evaluate the impact of the SCD SIMCS on access to screening and care and outcomes of children with SCD (R33 Phase). The investigators will pursue these aims using an innovative combination of software design and re-organization of SCD screening workflows. These include assembly of off-the-shelf software that is compatible with iOS and Android operating systems to reliably, accurately, and handily capture, interpret, transmit, and retrieve/playback information for patient's IDs, test results, salient clinical events, and education. The novel screening workflows are expected to dramatically reduce the cost and increase access to SCD screening and care. The proposed research is significant, because it will determine how to use POC SCD screening assays on a large nationwide scale. It will also enable coordination of evidence-based care and continuity of care between primary and specialist providers and longitudinally over the patient's lifetime - a critical aspect in controlling this life-long disease. The SCD SIMCS will also facilitate real time data management for research and policy for SCD control. The expected immediate outcome of this research is a SCD SIMCS that optimally functions on the digital and health infrastructure in Uganda and demonstration of its impact on access to SCD screening and care and on clinical outcomes of children with SCD. The expected long-term outcome is that the SCD SIMCS will be adopted, integrated, and scaled-up in the health systems of Uganda and other sub-Sahara Africa countries, particularly those where the POC assays have already been adopted as the national standard of SCD screening. If effective, the SCD SIMCS will have an important positive impact because it will reduce the cost of SCD screening, take screening services and evidence-based care closer to rural communities where the majority of children in sub-Sahara Africa live, and, ultimately, save millions of children from preventable and disability death.

The goal of this community based observation study is to co-create solutions that empower people to make informed decisions about epilepsy, reduce stigma, and promote community health among the adolescent population living with epilepsy in Uganda. The main objectives of the study are to: Goal 1: Co-create a unique patient-community engagement program (CEP) to reduce stigma on epilepsy among adolescents and their caregivers in Uganda based on understanding of the illness. Goal 2: Evaluate the impact of this CEP to reduce stigma on epilepsy among adolescents and their caregivers in Uganda, based on understanding of the illness. Study participants together with the relevant community stakeholders will co-design feasible communication and activity-based change projects that are based on both cultural and scientific norms, to reduce epilepsy stigma in the community Researchers will then compare the Quality of Life, Attitudes and Beliefs about Living with Epilepsy scores (as a surrogate of stigmatizing beliefs and practices among community members) and the Kilifi Stigma Scale scores in two parishes (urban and rural) to see if there is improvement in these assessments scores following the implementation of the community change projects.

The TokomezaPlus Ebola trial is a phase I/II double blind randomised clinical trial designed to assess the safety and immunogenicity of candidate SUDV vaccines in Uganda during the inter outbreak period. Uganda is prone to Ebola virus disease outbreaks especially those caused by the Ebola Sudan (SUDV) species. TokomezaPlus Ebola Vaccine trial protocol has two main components: a) Safety b) Immunogenicity and is designed to create a living protocol that will be used to study the safety and immunogenicity of SUDV-candidate vaccines in the East African EVD-prone countries.

A community-based Phase III, cluster randomized trial that seeks to determine the 24 week survival with retention in care of point of care CD4 testing with visitect and an enhanced package of screening and prophylaxis for opportunistic infections among patients with advanced HIV disease.