HIV Infections
Conditions
Keywords
HIV/AIDS, Medication Therapy Management, Treatment Adherence, Randomized Controlled Trial, Adverse Drug Events
Brief summary
This clinical trial aims to evaluate the effectiveness and cost-effectiveness of two levels of a pharmacist-led Medication Therapy Management (MTM) program, Basic MTM and Enhanced MTM, compared with usual care for HIV patients at high risk of adverse drug events in Khartoum, Sudan. The primary objective is to determine whether Basic MTM or Enhanced MTM improves medication adherence, measured by the Proportion of Days Covered (PDC ≥95%) at the primary 6-month assessment, with follow-up continuing for 24 months. Secondary objectives include evaluating the effects of the interventions on viral load suppression, CD4+ cell count, adverse drug events, drug-related problems, health-related quality of life, patient satisfaction, treatment self-efficacy, and cost-effectiveness. Participants will be randomly assigned in a 1:1:1 ratio to one of three study groups: Arm 1: Usual Care Arm 2: Basic Medication Therapy Management (Basic MTM) Arm 3: Enhanced Medication Therapy Management (Enhanced MTM) All participants will attend study visits at baseline and at 6, 12, 18, and 24 months to complete study questionnaires and undergo routine clinical assessments, including viral load and CD4+ measurements. Participants assigned to the Basic MTM group will receive usual care plus structured pharmacist-led Medication Therapy Management, including comprehensive medication reviews, a personal medication record, a medication action plan, five face-to-face MTM visits (baseline and every six months thereafter), and four scheduled telephone follow-up calls over the 24-month study period. Participants assigned to the Enhanced MTM group will receive all components of Basic MTM together with more frequent face-to-face visits, monthly during the first three months and every three months thereafter, additional telephone support for high-risk participants, adherence support tools (such as pill organizers and medication reminder tools), enhanced communication with prescribers, and home visits when appropriate. Do these MTM interventions improve clinical outcomes, such as viral load suppression and CD4+ cell count, compared to usual care? Researchers will compare three groups (Arm 1: Usual Care; Arm 2: Basic MTM; Arm 3: Enhanced MTM) to determine whether the MTM interventions lead to better medication adherence, fewer adverse drug events, improved quality of life, and greater cost-effectiveness. Participants will: Be randomly assigned to one of three groups: Usual Care, Basic MTM, or Enhanced MTM. Attend scheduled research assessment visits at baseline, 6, 12, 18, and 24 months to complete questionnaires (on adherence, quality of life, etc.) and provide blood samples for routine lab tests (viral load, CD4 count). If assigned to Basic MTM: Participate in 4 face-to-face sessions and 4 telephone follow-ups with a trained pharmacist over 24 months for medication reviews, education, and adherence support. If assigned to Enhanced MTM: Participate in 8 face-to-face sessions and 8 telephone follow-ups with a trained pharmacist over 24 months, and receive enhanced support tools (e.g., pillboxes, alarm devices) and potentially home visits.
Detailed description
This three-arm, parallel-group, open-label randomized controlled trial evaluates the effectiveness and cost-effectiveness of two levels of pharmacist-led Medication Therapy Management (MTM), Basic MTM and Enhanced MTM, compared with usual care among HIV patients at high risk of adverse drug events in Khartoum, Sudan. The study also includes an implementation evaluation guided by the Consolidated Framework for Implementation Research (CFIR). Participants are randomly assigned in a 1:1:1 ratio to one of three study arms using a computer-generated random sequence prepared by an independent statistician. Randomization is performed using variable block sizes and is stratified by study site and baseline viral suppression status. Allocation concealment is maintained using sequentially numbered, sealed, opaque envelopes opened only after completion of baseline assessments. Because of the nature of the MTM intervention, participants and pharmacist investigators are not blinded to treatment allocation. Laboratory personnel responsible for viral load and CD4 measurements and the independent statistician performing the primary analyses remain blinded to treatment allocation. The primary analysis follows the intention-to-treat principle and includes all randomized participants. Missing outcome data are handled using multiple imputation by chained equations (MICE). A prespecified per-protocol sensitivity analysis includes participants who complete at least 80% of scheduled MTM visits and have complete outcome data. Primary and secondary outcomes are assessed over a 24-month follow-up period using appropriate statistical methods specified in the study protocol. The study includes clinical, patient-reported, economic, and implementation outcomes, including medication adherence, viral load suppression, CD4+ cell count, adverse drug events, drug-related problems, health-related quality of life, treatment self-efficacy, patient satisfaction, and cost-effectiveness. Study oversight is provided by the Trial Steering Committee, which reviews study progress and data annually. No formal interim analyses or stopping rules are planned because the study evaluates a low-risk pharmacist-led behavioral intervention. Any protocol deviations are documented and managed according to the study protocol.
Interventions
BEHAVIORALBasic MTM
A structured pharmacist-led Medication Therapy Management (MTM) program delivered over 24 months in addition to usual care. The intervention includes comprehensive medication reviews (CMRs), development of a Personal Medication Record (PMR) and a Medication Action Plan (MAP), patient education, medication adherence assessment and support, identification and resolution of drug-related problems, and pharmacist communication with prescribers when appropriate. Participants receive five face-to-face MTM visits at baseline and every 6 months thereafter (months 0, 6, 12, 18, and 24), together with four scheduled telephone follow-up calls at months 3, 9, 15, and 21. Participants in this group do not receive the additional support components provided in the Enhanced MTM intervention.
BEHAVIORALEnhanced MTM
An enhanced pharmacist-led Medication Therapy Management (MTM) program delivered over 24 months in addition to usual care. The intervention includes all components of the Basic MTM program, including comprehensive medication reviews (CMRs), a Personal Medication Record (PMR), a Medication Action Plan (MAP), patient education, medication adherence assessment and support, identification and resolution of drug-related problems, and pharmacist communication with prescribers when appropriate. Participants receive more frequent face-to-face MTM visits, monthly during the first 3 months and every 3 months thereafter, together with additional telephone follow-up for high-risk participants. Enhanced MTM also includes structured peer support group sessions, adherence support tools (including pill organizers and medication reminder tools), enhanced collaboration with prescribers through multidisciplinary team particip
Sponsors
Universiti Sains Malaysia
Federal Ministry of Health, Sudan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
DOUBLE (Investigator, Outcomes Assessor)
Masking description
This is an open-label trial for participants, pharmacist investigators, and study coordinators because of the nature of the pharmacist-led behavioral intervention. Laboratory personnel responsible for viral load and CD4+ measurements and the independent statistician performing the primary analyses remain blinded to treatment allocation. Study data are identified using unique participant study IDs, and treatment groups are coded during statistical analysis to maintain assessor blinding where applicable.
Intervention model description
This is a three-arm, parallel-group, superiority randomized controlled trial with 1:1:1 allocation comparing Usual Care, Basic Medication Therapy Management (MTM), and Enhanced Medication Therapy Management (MTM). Participants are randomly assigned using a computer-generated sequence with block randomization stratified by study site and baseline viral suppression status. The study evaluates the comparative effectiveness, implementation, and cost-effectiveness of the two pharmacist-led MTM interventions over a 24-month follow-up period.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age: ≥18 years at the time of enrollment. * HIV Status: Laboratory-confirmed HIV infection. * ART Duration: Receiving antiretroviral therapy (ART) for at least 3 months prior to enrollment. --Language and Consent: Able to communicate in Arabic or English and willing and able to provide written informed consent. * High-Risk Status: Meeting at least 2 of the following high-risk criteria: * Receiving ≥8 chronic medications, including ART and medications for comorbidities. * Having ≥3 chronic comorbidities (e.g., diabetes mellitus, hypertension, hepatitis, or tuberculosis). * Documented or self-reported adverse drug event within the previous 12 months. * Viral load \>200 copies/mL during the previous 6 months. --Self-reported medication adherence \<95% or repeated missed clinic appointments. * Attendance at the participating HIV clinic on at least 2 occasions during the assessment period.
Exclusion criteria
* Age \<18 years. * Pregnancy. * Significant cognitive impairment preventing informed consent or study participation. * Terminal illness with expected life expectancy \<12 months. * Concurrent participation in another pharmacological intervention study. * Previous participation in a formal Medication Therapy Management (MTM) program within the past year. * Planned relocation away from Khartoum State during the follow-up period. * Inability to provide informed consent for any reason.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Medication Adherence - Proportion of Days Covered (PDC) | Baseline, 6 months (primary endpoint), 12 months, 18 months, and 24 months | Medication adherence will be assessed using the Proportion of Days Covered (PDC) calculated from pharmacy refill records as: (days covered by dispensed medication ÷ days in the observation period) × 100. Optimal adherence is defined as PDC ≥95%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Viral Load Suppression | Baseline, 6 months, 12 months, 18 months, 24 months | Proportion of participants achieving plasma HIV RNA \<200 copies/mL at each assessment time point |
| CD4+ Cell Count | Baseline, 6 months, 12 months, 18 months, 24 months | Absolute CD4+ T-lymphocyte count measured by flow cytometry. Analyses include the change in CD4+ cell count from baseline and the proportion of participants achieving CD4+ cell counts \>500 cells/µL. |
| Adverse Drug Events (ADEs) - Incidence | From enrollment through 24 months | Number and severity of adverse drug events (ADEs) occurring during the study period. ADEs are defined as any untoward medical occurrence associated with medication use and are classified according to standardized severity criteria. |
| Adverse Drug Events (ADEs) - Severity Distribution | From enrollment through 24 months | Distribution of adverse drug events (ADEs) according to severity (mild, moderate, severe, and life-threatening) using standardized severity classification criteria. Results will be reported as the proportion of ADEs within each severity category. |
| Drug-Related Problems (DRPs) | Baseline, 6 months, 12 months, 18 months, and 24 months (MTM arms only) | Number and types of drug-related problems (DRPs) identified using the modified Pharmaceutical Care Network Europe (PCNE) Classification Version 9.1. DRPs will be classified according to PCNE categories and reported as the number of DRPs identified per participant. |
| Medication Self-Efficacy Score | Baseline, 6 months, 12 months, 18 months, 24 months | Medication self-efficacy assessed using the HIV Treatment Adherence Self-Efficacy Scale (HIV-ASES), a 12-item instrument in which each item is rated on a scale from 0 (cannot do at all) to 10 (certain can do). Total scores range from 0 to 120, with higher scores indicating greater self-efficacy and confidence in taking medications as prescribed." |
| Number of Hospitalizations | From enrollment through 24 months | Total number of hospitalizations during the 24-month study period, including the reason for hospitalization (HIV-related or non-HIV-related) and the cumulative duration of hospitalization. Hospitalizations will be identified from medical records and study documentation. |
| Number of Emergency Department Visits | From enrollment through 24 months | Total number of emergency department visits during the 24-month study period, including the primary reason for each visit. Emergency department visits will be identified from medical records and study documentation. |
| Health-Related Quality of Life (EQ-5D-3L Index Score) | Baseline, 6 months, 12 months, 18 months, and 24 months | Health-related quality of life assessed using the EuroQol Five-Dimension Three-Level (EQ-5D-3L) descriptive system. Responses across the five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each rated on three levels, are converted to a single health utility index score using the \[specify value set, used., UK\] validated value set. Index scores range from -0.594 to 1.0 (using the UK value set; the exact minimum varies by value set), where 1.0 represents full health, 0 represents a health state equivalent to death, and negative values represent health states considered worse than death. Higher scores indicate better health-related quality of life." Note : why choosing (e.g. UK, Arab-region proxy) since Sudan does not yet have a locally derived value set. The minimum value will depend on that choice and should be explicitly stated. |
| Health-Related Quality of Life - EQ-VAS Score | Baseline, 6 months, 12 months, 18 months, 24 months | Health-related quality of life assessed using the EuroQol Visual Analogue Scale (EQ-VAS). Participants rate their overall health on a visual analogue scale from 0 (worst imaginable health) to 100 (best imaginable health), with higher scores indicating better perceived health. |
| Patient Satisfaction with Pharmaceutical Care | 6 months, 12 months, 18 months, and 24 months (MTM arms only) | Patient satisfaction with pharmacist-provided pharmaceutical care assessed using a modified version of the Pharmaceutical Care Satisfaction Questionnaire (PCSQ). The modified instrument comprises \[X\] items, each rated on a \[Y\]-point Likert scale (e.g., 1 = strongly disagree to \[Y\] = strongly agree). Total scores range from \[minimum\] to \[maximum\], with higher scores indicating greater satisfaction with the pharmaceutical care services received." |
| Direct Medical Costs | From enrollment through 24 months | Total direct medical costs from the healthcare system perspective, including costs associated with hospitalizations, emergency department visits, outpatient visits, laboratory tests, medications, and delivery of Medication Therapy Management (MTM) services. Costs will be reported in Sudanese Pounds (SDG) and converted to US Dollars (USD) using the prespecified exchange rate. |
| Serious Adverse Events (SAEs) | From enrollment through 24 months | Number of serious adverse events (SAEs) occurring during the study period. An SAE is defined as any adverse event resulting in death, a life-threatening condition, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or another medically important event. |
| Medication Knowledge Score | Baseline, 6 months, 12 months, 18 months, and 24 months | Medication knowledge assessed using a validated 15-item medication knowledge questionnaire. Each correct response is assigned one point, with total scores ranging from 0 to 15. Higher scores indicate better medication knowledge. Medication knowledge assessed using the Note : This is a study-specific instrument developed for this trial, state: "a validated 15-item Medication Knowledge Questionnaire (MKQ) developed and validated for the purposes of this study." |
Countries
Sudan
Contacts
STUDY_CHAIRHasni Arsad Ibrahim, PhD
Universiti Sains Malaysia
STUDY_DIRECTORMohd Yusmaidie Aziz, PhD
Universiti Sains Malaysia
STUDY_DIRECTORChristina Malini Christopher, PhD
Universiti Sains Malaysia (USM)
Outcome results
None listed