ENHANCE-EvideNce Led Co-created HeAlth Systems interventioNs for MLTCs CarE (ENHANCE)

Effectiveness of a Health Systems Strengthening Intervention to Improve Detection, Treatment, and Control of Multiple Long-Term Conditions in Primary Health Care Facilities in the Western Cape and KwaZulu Natal, South Africa

The goal of this study is to determine the effect of the ENHANCE intervention in improving clinical outcomes and evaluating the effects of the intervention on implementation processes and outcomes. The specific questions it aims to answer are:

1. To test and estimate the effect of the intervention in people with MLTCs attending

   PHCs on:

   i. Detection of, and initiation of treatment for, additional chronic conditions ii. Treatment intensification and changes in medication iii. Control of chronic conditions iv. patient reported health-related quality of life and functioning v. health care utilisation and adherence vi. costs of health care

2. To use the RE-AIM framework to assess implementation processes and outcomes through measurements of reach, adoption, implementation, and maintenance.
3. To understand implementation processes and outcomes within the wider context of primary healthcare, provide explanations for the observed effects of the clinical findings and identify recommendations for wider implementation of the ENHANCE intervention.

The participants in the control group will receive usual care at their primary health care facility, which includes the use of the Practical Approach to Care Kit (PACK) or Adult Primary Care (APC) clinical decision support tool. Participants in the intervention group will receive care for their multiple chronic condition by a clinician trained to use the ENHANCE clinical decision support tool (intervention tool), and receive two CHW visits in their home to provide treatment literacy and adherence support.

Study Overview

• Status: Completed
• Conditions: Depression; Myocardial Infarction; HIV Infections; Stroke; Hypertension; Diabetes Mellitus; Asthma
• Intervention / Treatment: Other: ENHANCE intervention (health systems)

Detailed Description

Control facilities Participants in control facilities will continue to receive usual care. Primary health care of long-term conditions is delivered free-at-point-of-care in public sector primary care facilities which includes the management of HIV, NCDs and mental health problems, according to South Africa's Ideal Clinic and Integrated Clinical Services Management model. This care model, which has combined the long-term care of HIV together with NCDs within each facility, has greatly enabled the feasibility of further interventions specifically addressing MLTCs and includes the Adult Primary Care (APC) or PACK clinical guidance. Patients attending these chronic services usually attend the same clinic regularly, 3 to 6-monthly for periodic monitoring of their chronic conditions. Chronic medication is collected monthly either at the facility (through fast-track queues), or through decentralised chronic medication dispensing systems which provide for collection from a range of sites including community venues (e.g. halls), wellness or adherence clubs, trailers, retail pharmacies (in KZN) or e-Lockers.

Intervention clinics

Participants in intervention clinics will continue with usual care as described for control clinics but in addition will receive the ENHANCE health systems intervention comprising tools and implementation strategies that have been co-developed with stakeholders through an iterative process, drawing on:

i. Evidence on the commonest MLTC combinations ii. Scoping reviews conducted on effectiveness of MLTCS interventions and systems barriers and enablers of person-centred care for MLTCs in LMICs iii. Provincial and district learning collaborative workshops with stakeholders from KZN and Western Cape.

iv. Clinical working groups with clinicians and health workers, a Guidance Oversight Board v. Input from our ENHANCE advocacy academy of 16 people living with MLTCs in the Western Cape and KZN

The intervention targets screening and early identification of other chronic conditions; improving follow-up and support for people with a new diagnosis, at risk of treatment failure (e.g. poorly controlled HIV or diabetes), and strengthen bi-directional referral pathways between the facility and community. Tools and implementation strategies will be layered into existing architecture of the chronic care system and support provision of more person-centred and empowering care across the treatment cascade.

Tools to support the implementation of the health systems intervention comprise:

• An integrated clinical decision support tool for care of MLTCs drawing on PACK/ APC.
• A range of patient-focussed materials to support condition, treatment, and systems (care-seeking) literacy (e.g., medication list, posters, scripts for health education talks)
• A personal health diary (paper-based)

Implementation strategies include:

• 1 facility team session to introduce the ENHANCE study to the whole team
• 3 clinical sessions for nurses and doctors
• 2 sessions for community health workers and health promoters
• Maintenance sessions to keep the ENHANCE intervention going for at least 12 months.

• Study Type: Interventional
• Enrollment (Actual): 1837
• Phase: Not Applicable

Contacts and Locations

Study Locations

• South Africa
  • Pietermaritzburg, South Africa
    • Caluza Clinic
  • KwaZulu-Natal
    • Pietermaritzburg, KwaZulu-Natal, South Africa
      • Eastwood Clinic
    • Pietermaritzburg, KwaZulu-Natal, South Africa
      • Esigodini Clinic
    • Pietermaritzburg, KwaZulu-Natal, South Africa
      • Gcumisa Clinic
    • Pietermaritzburg, KwaZulu-Natal, South Africa
      • Gomane Clinic
    • Pietermaritzburg, KwaZulu-Natal, South Africa
      • Howick Clinic
    • Pietermaritzburg, KwaZulu-Natal, South Africa
      • Impilwenhle Clinic
    • Pietermaritzburg, KwaZulu-Natal, South Africa
      • Injabulo Clinic
    • Pietermaritzburg, KwaZulu-Natal, South Africa
      • Mafatini Clinic
    • Pietermaritzburg, KwaZulu-Natal, South Africa
      • Mphophomeni Clinic
    • Pietermaritzburg, KwaZulu-Natal, South Africa
      • Ndaleni Clinic
    • Pietermaritzburg, KwaZulu-Natal, South Africa
      • Northdale Clinic
    • Pietermaritzburg, KwaZulu-Natal, South Africa
      • Pata Clinic
    • Pietermaritzburg, KwaZulu-Natal, South Africa
      • Richmond Clinic
    • Pietermaritzburg, KwaZulu-Natal, South Africa
      • Songonzima Clinic
    • Pietermaritzburg, KwaZulu-Natal, South Africa
      • Willowfontein CHC
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7700
      • Delft CHC
    • Cape Town, Western Cape, South Africa, 7700
      • Dr Abdurahman CHC
    • Cape Town, Western Cape, South Africa, 7700
      • DuNoon CHC
    • Cape Town, Western Cape, South Africa, 7700
      • Durbanville CHC
    • Cape Town, Western Cape, South Africa, 7700
      • Elsies CHC
    • Cape Town, Western Cape, South Africa, 7700
      • Gugulethu CHC
    • Cape Town, Western Cape, South Africa, 7700
      • Gustrouw CDC
    • Cape Town, Western Cape, South Africa, 7700
      • Hanover Park CHC
    • Cape Town, Western Cape, South Africa, 7700
      • Heideveld CHC
    • Cape Town, Western Cape, South Africa, 7700
      • Kleinvlei CHC
    • Cape Town, Western Cape, South Africa, 7700
      • Kraaifontein CHC
    • Cape Town, Western Cape, South Africa, 7700
      • Macassar CDC
    • Cape Town, Western Cape, South Africa, 7700
      • Michael M
    • Cape Town, Western Cape, South Africa, 7700
      • Mitchells Plain CHC
    • Cape Town, Western Cape, South Africa, 7700
      • Retreat CHC
    • Cape Town, Western Cape, South Africa, 7700
      • Vanguard CHC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults aged 40 years or older

• Receiving care for at least two of the following conditions, with at least one of the first five listed conditions being uncontrolled or patients indicated as struggling with the management of their condition:

  i. HIV (Self-reported current treatment). ii. hypertension (Self-reported current treatment. iii. diabetes (Self-reported current treatment). iv. asthma (Self-reported current treatment). vi. depression (Self-reported current treatment). vii. previous myocardial infarction (self-reported). viii. previous stroke (self-reported history).

Exclusion Criteria:

• Participants planning to relocate from either uMgungundlovu, KwaZulu-Natal, and Cape Metro in Western Cape, or changing their facilities during the period of the study.
• Participants who are unable to give informed consent due to loss of capacity.
• Participants self-reporting pregnancy
• Participants who cannot communicate in English, isiXhosa, isiZulu, or Afrikaans.
• Participants who are not willing to receive care for chronic conditions in their homes.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Intervention; Treatment literacy in chronic condition waiting rooms/pick-up points (posters, health promotion talks); 1-2 longer consultations with ENHANCE guide trained clinician; Treatment literacy event - a contact between a CHW and a person with MLTC in their home (hopefully with carer), at 2 weeks and 4 weeks, using Health Diary; Referrals to additional adherence counselling if necessary	Other: ENHANCE intervention (health systems); The intervention tools include a consolidated clinical decision support tool, health education posters, waiting room talks, medication list for treatment literacy and a patient health diary. Training session are delivered at all intervention sites and include 1 facility team session to introduce the ENHANCE study to the whole team; 3 clinical sessions for nurses and doctors; 2 sessions for community health workers and health promoters; Maintenance sessions to keep the ENHANCE intervention going for at least 12 months
No Intervention: Control; Usual care at primary health care clinic, which includes consultation with a clinician using the PACK/APC guide. No additional support is usually provided for care of MLTCs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite outcome: Diagnosis and treatment initiation for a new condition, intensification or change of treatment for a condition treated at enrolment, or improved control for a condition not optimally controlled at enrolment.	Number of participants who meet any of the following criteria during follow-up: . Diagnosis and initiation of treatment during follow-up of one or more additional chronic conditions,; . Intensification or change of treatment during follow-up for at least one of the chronic conditions present and treated at enrolment, or,; . Improved control of at least one condition that was not optimally controlled at baseline, defined as follows: HIV - viral suppression (viral load <50 copies/mL); hypertension - systolic blood pressure<140 mmHg and diastolic blood pressure less than 90mmHg; diabetes - HbA1c <8%, asthma - Asthma Control Test score ≥16, depression - Patient Health Questionnaire 8 (PHQ-8) <10	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnosis and initiation of treatment during follow-up of one or more additional chronic conditions	The number of participants having a diagnosis and treatment initiation during follow-up of one or more additional chronic conditions	12 months
Intensification or change of treatment during follow-up for at least one of the chronic conditions present and treated at enrolment	The number of participants with intensification or change of treatment during follow-up for at least one of the chronic conditions present and treated at enrolment	12 months
Improved control of at least one condition that was not optimally controlled at baseline	The number of participants with improved control of at least one condition that was not optimally controlled at baseline, defined as follows: HIV - viral suppression (viral load <50 copies/mL); hypertension - systolic blood pressure<140 mmHg and diastolic blood pressure less than 90mmHg; diabetes - HbA1c <8%, asthma - Asthma Control Test score ≥16, depression - Patient Health Questionnaire 8 (PHQ-8) <10	12 months
World Health Organisation Disability Assessment Schedule 2.0 score	Mean functional disability score assessed using the 12-item WHODAS-2.0 (World Health Organisation Disability Assessment Schedule 2.0) tool. The scores range from 0-100, with higher scores indicating more functional limitations/disability	12 months
Health-related quality of life EuroQol 5-Dimension 5-Level score	Mean health-related quality of life score assessed using the EuroQol 5D-5L (EQ5D-5L). The EQ5D-5L score ranges from -0.493 (indicating the worst health state) to 1 (indicating the best health state	12 months
Health-related quality of life visual analogue scale score	Mean self-reported health-related quality of life score assessed using a visual analogue scale (VAS). The VAS score ranges from 0-100, with higher scores indicating better health status.	12 months
Patient Assessment of Chronic Illness Care	Mean Patient Assessment of Chronic Illness Care (PACIC) score. The score ranges from 1 - 5, with lower scores indicating worse satisfaction with chronic care and higher scores indicating more satisfaction	12 months
Patient experience with treatment and self-management	Mean scores for patient experience with treatment and self-management (PETS), assessed using a shortened version of the PETS tool. The tool has no overall score and uses domain scores with different ranges. Lower scores indicate more difficulty, and higher scores indicate more ease.	12 months
Patient Health Questionnaire-8 (PHQ-8) score	Mean scores for depressive symptoms assessed using the patient health questionnaire-8 (PHQ-8) tool. The score ranges from 0-24, with higher scores indicating worse depressive symptoms	12 months
Social Support	Number of patients reporting having social support for their care and medical needs, and mean social support score	12 months
Healthcare utilisation - Number of clinic visits	Number of clinic visits	12 months
Healthcare utilisation - Number of hospital outpatient visits	Number of hospital outpatient visits	12 months
Healthcare utilisation - hospital admissions	Number of hospital admissions	12 months
Healthcare utilisation - hospital admission days	Number of hospital in-patient days	12 months
Health care costs	The costs of accessing healthcare	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Implementation	Reach, adoption and implementation, and maintenance of the ENHANCE intervention: Exposure of PHC staff and patients to elements of the intervention and implementation strategy,; Integration of intervention components into care; Appropriateness of new diagnoses and treatment; Patient, clinician and CHW perceptions of the acceptability of the ENHANCE intervention and associated barriers and facilitators to its implementation	12 months

Collaborators and Investigators

• Sponsor: University of KwaZulu
• Collaborators: King's College London; University of Oxford; University of East Anglia; University of Cape Town; Medical Research Council, South Africa
• Investigators: Study Chair: Lara Fairall, PhD, King's College London

Publications and helpful links

General Publications

• Nguyen H, Manolova G, Daskalopoulou C, Vitoratou S, Prince M, Prina AM. Prevalence of multimorbidity in community settings: A systematic review and meta-analysis of observational studies. J Comorb. 2019 Aug 22;9:2235042X19870934. doi: 10.1177/2235042X19870934. eCollection 2019 Jan-Dec.
• COVID-19 Mental Disorders Collaborators. Global prevalence and burden of depressive and anxiety disorders in 204 countries and territories in 2020 due to the COVID-19 pandemic. Lancet. 2021 Nov 6;398(10312):1700-1712. doi: 10.1016/S0140-6736(21)02143-7. Epub 2021 Oct 8.
• Peer N, Uthman OA, Kengne AP. Rising prevalence, and improved but suboptimal management, of hypertension in South Africa: A comparison of two national surveys. Glob Epidemiol. 2021 Sep 10;3:100063. doi: 10.1016/j.gloepi.2021.100063. eCollection 2021 Nov.
• Mayosi BM, Flisher AJ, Lalloo UG, Sitas F, Tollman SM, Bradshaw D. The burden of non-communicable diseases in South Africa. Lancet. 2009 Sep 12;374(9693):934-47. doi: 10.1016/S0140-6736(09)61087-4. Epub 2009 Aug 24.
• Oni T, Youngblood E, Boulle A, McGrath N, Wilkinson RJ, Levitt NS. Patterns of HIV, TB, and non-communicable disease multi-morbidity in peri-urban South Africa- a cross sectional study. BMC Infect Dis. 2015 Jan 17;15:20. doi: 10.1186/s12879-015-0750-1.
• Gouda HN, Charlson F, Sorsdahl K, Ahmadzada S, Ferrari AJ, Erskine H, Leung J, Santamauro D, Lund C, Aminde LN, Mayosi BM, Kengne AP, Harris M, Achoki T, Wiysonge CS, Stein DJ, Whiteford H. Burden of non-communicable diseases in sub-Saharan Africa, 1990-2017: results from the Global Burden of Disease Study 2017. Lancet Glob Health. 2019 Oct;7(10):e1375-e1387. doi: 10.1016/S2214-109X(19)30374-2.
• Kamkuemah M, Gausi B, Oni T. Missed opportunities for NCD multimorbidity prevention in adolescents and youth living with HIV in urban South Africa. BMC Public Health. 2020 Jun 1;20(1):821. doi: 10.1186/s12889-020-08921-0.
• Herman AA, Stein DJ, Seedat S, Heeringa SG, Moomal H, Williams DR. The South African Stress and Health (SASH) study: 12-month and lifetime prevalence of common mental disorders. S Afr Med J. 2009 May;99(5 Pt 2):339-44.
• Roomaney RA, van Wyk B, Turawa EB, Pillay-van Wyk V. Multimorbidity in South Africa: a systematic review of prevalence studies. BMJ Open. 2021 Oct 6;11(10):e048676. doi: 10.1136/bmjopen-2021-048676.
• Hurst JR, Dickhaus J, Maulik PK, Miranda JJ, Pastakia SD, Soriano JB, Siddharthan T, Vedanthan R; GACD Multi-Morbidity Working Group. Global Alliance for Chronic Disease researchers' statement on multimorbidity. Lancet Glob Health. 2018 Dec;6(12):e1270-e1271. doi: 10.1016/S2214-109X(18)30391-7. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2023
• Primary Completion (Actual): November 1, 2025
• Study Completion (Actual): November 1, 2025

Study Registration Dates

• First Submitted: January 17, 2024
• First Submitted That Met QC Criteria: January 30, 2024
• First Posted (Actual): February 8, 2024

Study Record Updates

• Last Update Posted (Actual): February 24, 2026
• Last Update Submitted That Met QC Criteria: February 20, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Person Centered Care; Multiple Chronic Conditions; Health Systems Intervention
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Chronic Disease; Disease Attributes; Metabolic Diseases; Immune System Diseases; Behavioral Symptoms; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Glucose Metabolism Disorders; Infarction; Necrosis; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Myocardial Ischemia; Ischemia; Pathological Conditions, Signs and Symptoms; Behavior; Nutritional and Metabolic Diseases; Multiple Chronic Conditions; Stroke; Hypertension; Asthma; HIV Infections; Depression; Diabetes Mellitus; Myocardial Infarction
• Other Study ID Numbers: 686/2022; 201816 (Other Grant/Funding Number: NIHR); BREC/00005033/2022 (Other Identifier: UKZN BREC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported, after deidentification (text, tables, figures, and appendices).
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication.
• IPD Sharing Access Criteria: Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No