Implementation of Out-of-HOspital Administration of the Long-Acting Cabotegravir+Rilpivirine

Study Overview
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Brief Summary
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HOLA is a prospective, randomized (1:1), hybrid type (implementation-effectiveness), phase IV, double arm, open label, multicentric study including virologically suppressed HIVinfected subjects who start or are currently under treatment with the LA antiretroviral combination CAB+RPV, to evaluate the out-of-hospital administration of this combination in terms of acceptability, appropriateness, feasibility and satisfaction.

Detailed Description
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Randomized patients will receive Long Acting (LA) cabotegravir (CAB) + rilpivirine (RPV) administration in the hospital (standard of care) or out-of-hospital administration every 2 months (M2, M4, M6, M8,M10, M12). Medical visits, routinary blood tests and pharmacy visits at the hospital of reference will take place every 6 months- at baseline, M1 (if patient has not previously receiving LA CAB+RPV), M6 and M12.

Official Title
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Implementation of Out-of-HOspital Administration of the Long-Acting Combination Cabotegravir+Rilpivirine as an Optional Therapy in HIV-Infected Patients From Spain: Acceptability, Appropriateness, Feasibility and Satisfaction: The HOLA Study

Conditions
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HIV-1 Infection

Intervention / Treatment
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* Drug: Hospital long-acting Vocabria (cabotegravir) 600 mg and long-acting Rekambys (rilpivirine) 900 mg administration
* Drug: Out of Hospital long-acting Vocabria (cabotegravir) 600 mg and long-acting Rekambys (rilpivirine) 900 mg administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients equal or older than 18 years old Chronic HIV infection HIV patients in whom LA CAB+RPV is prescribed Recommended triple or dual therapy for at least 12 months, including CAB+RPV LA. Virologically suppression for at least 6 months (2 consecutive determinations of undetectable viral load). Post-menopausal or fertile females that agree to avoid pregnancy during the study. If sexually active female; using an effective method of contraception (hormonal contraception, intra-uterine device (IUD), or anatomical sterility in self or partner) from 14 days prior to the first IMP administration until at least 13 months after the last Investigational Medicinal Product (IMP) administration;all female volunteers must be willing to undergo urine pregnancy tests at time points specified in the protocol. Patients which have access to an out of hospital center in which can be treated without inconvenience Patient who agrees to participate in the study and signs the informed consent. Exclusion Criteria: Hepatitis B infection (section 6.2). History of virological failure or mutations to INSTI or NNRTI. Previous antiretroviral treatment interruption during the last 6 months or treatment interruptions for more than a month. Contraindication for intramuscular injections Pregnancy or breastfeeding women, or with the desire to become pregnant in the near future. Current use of any concomitant treatment as indicated in section 5.6.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A 12-months prospective, hybrid type (implementation-effectiveness), phase IV, randomized (1:1), open label, multicentric study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Hospital Group<br>Administration of long-acting Vocabria (cabotegravir) 600 mg and long-acting Rekambys (rilpivirine) 900 mg in the hospital (standard of care) | Drug: Hospital long-acting Vocabria (cabotegravir) 600 mg and long-acting Rekambys (rilpivirine) 900 mg administration<br>* Hospital administration of long-acting Vocabria (cabotegravir) 600 mg and long-acting Rekambys (rilpivirine) 900 mg as standard of care.<br>* Other names: Administration of LA CAB+RPV in the hospital;|
| Experimental: Outpatient Group<br>Out-of-hospital administration of long-acting Vocabria (cabotegravir) 600 mg and long -acting Rekambys (rilpivirine) 900 mg | Drug: Out of Hospital long-acting Vocabria (cabotegravir) 600 mg and long-acting Rekambys (rilpivirine) 900 mg administration<br>* Out of Hospital administration of long-acting Vocabria (cabotegravir) 600 mg and long-acting Rekambys (rilpivirine) 900 mg as an optional therapy in HIV-Infected patients from Spain.<br>* Other names: Administration of LA CAB+RPV out of hospital;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the acceptability of the administration of LA CAB + RPV in Alternative Injection Facilities (AOF) from the perspective of participants receiving outside-hospital injections vs the participants receiving hospital injections. | Number of participants receiving injections that show an average composite score ≥ 4 across the AIM questionnaires. To asses the acceptability we will use the Acceptability Intervention Measure (AIM) questionnaire (item questionnaires that use a 5-point rating scale: 1 = completely disagree to 5 = completely agree). The higher score means the best outcome. | at month 12 | 
| Evaluate the acceptability of the administration of LA CAB + RPV in Alternative Injection Facilities (AOF) from the perspective of participants receiving outside-hospital injections vs the participants receiving hospital injections. | Proportion of participants receiving injections that show an average composite score ≥ 4 across the AIM questionnaires. To asses the acceptability we will use the Acceptability Intervention Measure (AIM) questionnaire (item questionnaires that use a 5-point rating scale: 1 = completely disagree to 5 = completely agree). The higher score means the best outcome. | at month 12 | 
| Evaluate the acceptability of the administration of LA CAB + RPV in Alternative Injection Facilities (AOF) from the perspective of participants receiving outside-hospital injections vs the participants receiving hospital injections. | Differences among the proportion of participants receiving injections with an average composite score ≥ 4 across the AIM questionnaires. To asses the acceptability we will use the Acceptability Intervention Measure (AIM) questionnaire (item questionnaires that use a 5-point rating scale: 1 = completely disagree to 5 = completely agree). The higher score means the best outcome. | at month 12 | 
| Evaluate the acceptability of the administration of LA CAB + RPV in Alternative Injection Facilities (AOF) from the perspective of participants receiving outside-hospital injections vs the participants receiving hospital injections. | To asses the acceptability we will use the Acceptability Intervention Measure (AIM) questionnaire (item questionnaires that use a 5-point rating scale: 1 = completely disagree to 5 = completely agree). The higher score means the best outcome. - Average composite score across the AIM questionnaires. | at month 12 | 
| Assess and compare the CAB + RPV LA - related adverse events (AEs) , all Serious Adverse Events (SAEs), injection site reactions (ISRs) or post injection reactions safety and tolerability of LA CAB+RPV (Safety and Tolerability) | Incidence and severity of CAB + RPV LA - related adverse events (AEs) , all Serious Adverse Events (SAEs), Injection site reactions (ISRs) or post injection reactions | through study completion, an average of 1 year | 
| Assess and compare the safety and tolerability of LA CAB+RPV. | Proportion of participants who discontinue CAB + RPV LA due to AEs/SAEs | through study completion, an average of 1 year | 
| Assess and compare the safety and tolerability of LA CAB+RPV. | Comparing between groups number and proportion of patients who withdraw treatment study due to antiretroviral-related adverse events and reasons | at month 6 and 12 | 
| Assess and compare the safety and tolerability of LA CAB+RPV. | Comparing between groups number and proportion of patients who presented grade 3 or 4 antiretroviral-related adverse events | at month 6 and 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess and compare the acceptability of the administration of LA CAB + RPV as perceived by patients at intermediate times of the study (month 1 and month 6). | Number of participants receiving injections with an average composite score ≥ 4 across the AIM questionnaires (item questionnaires that use a 5-point rating scale: 1 = completely disagree to 5 = completely agree) , as perceived by the patient. The higher score means the best outcome. | at month 1 and 6 | 
| To assess and compare the acceptability of the administration of LA CAB + RPV as perceived by patients at intermediate times of the study (month 1 and month 6). | Proportion of participants receiving injections with an average composite score ≥ 4 across the AIM questionnaires (item questionnaires that use a 5-point rating scale: 1 = completely disagree to 5 = completely agree) , as perceived by the patient.The higher score means the best outcome. | at month 1 and 6 | 
| To assess and compare the acceptability of the administration of LA CAB + RPV as perceived by patients at intermediate times of the study (month 1 and month 6). | Differences among the proportion of participants receiving injections with an average composite score ≥ 4 across the AIM questionnaires | at month 1 and 6. | 
| To assess and compare the acceptability of the administration of LA CAB + RPV as perceived by patients at intermediate times of the study (month 1 and month 6). | Average composite score across the AIM questionnaires (item questionnaires that use a 5-point rating scale: 1 = completely disagree to 5 = completely agree) at month 1 and 6. The higher score means the best outcome. | at month 1 and 6 | 
| To assess and compare appropriateness and feasibility of the administration of LA CAB + RPV as perceived by patients at month 1, month 6 and month 12. | Number of participants receiving injections with an average composite score ≥ 4 across the Intervention Appropriateness Measure( IAM) / Feasibility of Intervention Measure (FIM) questionnaires, (item questionnaires that use a 5-point rating scale: 1 = completely disagree to 5 = completely agree) as perceived by the patient. The higher score means the best outcome. | at months 1, 6 and 12 | 
| To assess and compare appropriateness and feasibility of the administration of LA CAB + RPV as perceived by patients at month 1, month 6 and month 12. | Proportion of participants receiving injections with an average composite score ≥ 4 across the Intervention Appropriateness Measure( IAM) / Feasibility of Intervention Measure (FIM) questionnaires (item questionnaires that use a 5-point rating scale: 1 = completely disagree to 5 = completely agree), as perceived by the patient.The higher score means the best outcome. | at months 1, 6 and 12 | 
| To assess and compare appropriateness and feasibility of the administration of LA CAB + RPV as perceived by patients at month 1, month 6 and month 12. | Differences among the proportion of participants receiving injections with an average composite score ≥ 4 across the IAM /FIM questionnaires (item questionnaires that use a 5-point rating scale: 1 = completely disagree to 5 = completely agree).The higher score means the best outcome. | at month 1, 6 and 12. | 
| To assess and compare appropriateness and feasibility of the administration of LA CAB + RPV as perceived by patients at month 1, month 6 and month 12. | Average composite score across the Intervention Appropriateness Measure (IAM) and Feasibility Intervention Measure (FIM) patient questionnaires (item questionnaires that use a 5-point rating scale: 1 = completely disagree to 5 = completely agree). The higher score means the best outcome. | at month 1, 6 and 12. | 
| To assess and compare the acceptability, appropriateness and feasibility of the administration of LA CAB + RPV as perceived by Healthcare Professionals (HCP)/non-clinical staff at study month 1 and month 6 and month 12. | Number of HCP and/or non- clinical staff that show an average composite score ≥ 4 across the Acceptability Intervention Measure (AIM), Intervention Appropriateness Measure (IAM) and Feasibility Intervention Measure (FIM) patient questionnaires questionnaires (item questionnaires that use a 5-point rating scale: 1 = completely disagree to 5 = completely agree).The higher score means the best outcome. . | at months 1, 6 and 12. | 
| To assess and compare the acceptability, appropriateness and feasibility of the administration of LA CAB + RPV as perceived by Healthcare Professionals (HCP)/non-clinical staff at study month 1 and month 6 and month 12. | Proportion of HCP and/or non- clinical staff that show an average composite score ≥ 4 across the AIM / IAM /FIM questionnaires (item questionnaires that use a 5-point rating scale: 1 = completely disagree to 5 = completely agree).The higher score means the best outcome. . | at months 1, 6 and 12. | 
| To assess and compare the acceptability, appropriateness and feasibility of the administration of LA CAB + RPV as perceived by HCP/non-clinical staff at study month 1 and month 6 and month 12. | Differences among the proportion of HCP/non-clinical staff with an average composite score ≥ 4 across the AIM / IAM /FIM questionnaires (item questionnaires that use a 5-point rating scale: 1 = completely disagree to 5 = completely agree).The higher score means the best outcome. | at month 1, 6 and 12. | 
| To assess and compare the acceptability, appropriateness and feasibility of the administration of LA CAB + RPV as perceived by HCP/non-clinical staff at study month 1 and month 6 and month 12. | Average composite score across the AIM / IAM /FIM questionnaires (item questionnaires that use a 5-point rating scale: 1 = completely disagree to 5 = completely agree).The higher score means the best outcome. | at month 1, 6 and 12. | 
| Patient's satisfaction and expectations | To compare between groups the percentage of patients who report high satisfaction at each study time-points using the HIV Treatment Satisfaction Questionnaire (HIVTSQs12). This scale includes 11 items which are summed to form an 11-item scale score and one item, item 12 (pain/discomfort) is treated as an individual item score. | baseline and months 1, 6 and 12 | 
| Patient's satisfaction and expectations | To assess changes in satisfaction derived from HIV Treatment Satisfaction Questionnaire status (HIVTSQs12), in the overall sample. | from baseline to months 1, 6 and 12 | 
| Patient's satisfaction and expectations | To assess changes in satisfaction derived from HIV Treatment Satisfaction Questionnaire change (HIVTSQc12) in the overall sample. | from baseline to month 12 | 
| Patient's satisfaction and expectations | To assess and compare among groups the expectations of the LA CAB+RPV regarding the following areas: adherence to treatment, follow-up of medical visits, illness perception, physical and emotional quality of life, family and social relationships and work. Expectations will be assessed through 5-likert scales developed ad hoc for the study | at baseline and month 6 and 12 | 
| Patient's satisfaction and expectations | To compare among groups the Patient Reported Outcome Measures (PROMs) at each study time-points using the Patient Reported Outcome Measures HIV Clinic Screening Tool (PROMS-CST- HIV) questionnaire. This questionnaire assesses PRO regarding anticipated stigma, emotional distress, sexuality, social support, material deprivation, sleep and fatigue, cognitive problems, physical symptoms. | baseline and months 1, 6 and 12 | 
| Patient's satisfaction and expectations | To assess changes in the Patient Reported Outcome Measures (PROMs) throughout the time points in each group in the overall sample using the Patient Reported Outcome Measures HIV Clinic Screening Tool (PROMS-CST- HIV) questionnaire. This questionnaire assesses PRO regarding anticipated stigma, emotional distress, sexuality, social support, material deprivation, sleep and fatigue, cognitive problems, physical symptoms. | from baseline to months 1, 6 and 12 | 
| Patient's satisfaction and expectations | To compare changes in the health professionals 'expectations using a Health Professional Expectations Questionnaire. | through study completion, an average of 1 year | 
| Patient's satisfaction and expectations | To compare the perception of injection, using the perception of injection (PIN) questionnaire. | month 1, 2,4,6,8,10 and month 12. | 
| Retention, engagement and compliance | To compare among groups number of patients who miss their appointment for the LA CAB+RPV administration (out of the window period ±7 days) | from baseline to month 6 and 12 | 
| Retention, engagement and compliance | To compare among groups proportion of patients who miss their appointment for the LA CAB+RPV administration (out of the window period ±7 days) | from baseline to month 6 and 12 | 
| Retention, engagement and compliance | To compare among groups number of patients who early interrupt LA CAB+RPV every 2 months | at month 6 and 12. | 
| Retention, engagement and compliance | To compare among groups proportion of patients who early interrupt LA CAB+RPV every 2 months | at month 6 and 12. | 
| Retention, engagement and compliance | To compare among groups number of patients who withdraw treatment study | at month 6 and 12. | 
| Retention, engagement and compliance | To compare among groups proportion of patients who withdraw treatment study | at month 6 and 12. | 
| Retention, engagement and compliance | Time to LA CAB + RPV discontinuation. | through study completion, an average of 1 year | 
| Retention, engagement and compliance | To compare among groups the number of patients who adopt oral bridging therapy | during the 12 months of study. | 
| Retention, engagement and compliance | To compare among groups the proportion of patients who adopt oral bridging therapy | during the 12 months of study. | 
| To identify those patients in which the out-of-hospital administration is more suitable. | To identify those patients in which the out-of-hospital administration is more suitable by comparing the previous endpoints, stratifying according to: age (< vs >50 years old), gender (male vs female), as well as according to if the participant is already receiving or not LA CAB+RPV. | through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-1, long acting, primary center, community center, out-of-hospital by implementation, cabotegravir + rilpivirine (CAB+RPV)