Treatment of Early Hypertension Among Persons Living With HIV in Haiti

• ClinicalTrials.gov Identifier: NCT04692467
• Recruitment Status: Recruiting
• First Posted: December 31, 2020
• Last Update Posted: December 21, 2021
• Sponsor: Weill Medical College of Cornell University
• Collaborators: Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic; Fogarty International Center of the National Institute of Health
• Information provided by (Responsible Party): Weill Medical College of Cornell University

Study Description

Brief Summary:

The investigators are conducting an unblinded pilot randomized control trial of 250 persons living with HIV (PLWH), aged 18-65 years, who receive antiretroviral therapy care at Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic Infections (GHESKIO), are virally suppressed, and have pre-hypertension (systolic blood pressure (SBP) 120-139 or diastolic blood pressure (DBP) 80-89 mmHg) to be randomized to early hypertension (HTN) treatment versus standard of care (SOC). Participants will be recruited from GHESKIO's HIV clinic. Eligible individuals will complete informed consent and be randomized to early HTN treatment vs. SOC. Participants in early HTN treatment will initiate amlodipine immediately versus those in SOC will initiate amlodipine only if they meet the HTN threshold (SBP ≥140 or DBP ≥90 mmHg) during the study period. All participants will be followed for 12 months.

Condition or disease	Intervention/treatment	Phase
HIV/AIDS; Pre Hypertension	Drug: Amlodipine 5mg	Phase 2

Detailed Description:

The investigators propose a pilot randomized controlled trial to evaluate antihypertensive treatment among people living with HIV (PLWH) with pre-hypertension (pre-HTN) at GHESKIO. This study will provide critical data on the feasibility, benefits and risks of antihypertensive treatment for cardiovascular disease (CVD) prevention among PLWH with pre-HTN that will inform a future definitive trial powered for incident CVD events.

For the pilot study, the investigators will enroll 250 PLWH (18-65 years of age) who have been on antiretroviral therapy (ART) for ≥ 1 years with viral suppression within past 12 months and SBP 120-139 or DBP 80-89 mm Hg and no current antihypertensive treatment; randomize them to "early HTN treatment" or the current standard of care (SOC); and follow them for 12 months. Amlodipine is the recommended first-line anti-hypertensive medication according to Haiti's new primary care HTN guidelines. Participants in the early HTN treatment arm will initiate amlodipine 5 mg immediately, increasing to 10 mg if SBP >130 mm Hg after 1 month. Participants in the SOC arm will initiate amlodipine only if they develop HTN (SBP ≥140 or DBP ≥90 mm Hg).

Participants that meet study eligibility criteria will proceed to study enrollment visit (~90 min). Participants will be randomized to early HTN treatment vs. SOC in a 1:1 ratio using a computer-generated random assignment. The research nurse will collect demographic and clinical data, administer a baseline questionnaire, measure unobserved BP, and perform an ECG. The questionnaire includes a CVD medical history, family history, medications, CVD health behaviors (smoking, alcohol, physical activity, and diet) using validated questions that have been used at GHESKIO and are comparable to those used in US cohorts. Enrollment labs (~15ml of venous blood) including HgbA1c, total cholesterol, high density cholesterol, CD4 cell count, and HIV viral load (unless available from electronic medical record in the past 6 months) will be collected. Samples of serum and plasma will be stored for future studies, with documented consent from participants. The study physician will interpret the ECG and perform an echocardiogram and vascular ultrasound.

Study drug will be dispensed to participants randomized to the early treatment arm with appropriate education and counseling on adherence and potential side effects. Amlodipine will be started at 5mg at enrollment and increased to 10mg if SBP >130 mm Hg after 1 month for participants in the early treatment arm. Locator and contact information will be verified and follow up appointment given.

After enrollment and randomization assignment (including amlodipine initiation), participants will have follow-up visits either at GHESKIO (months 0.5-1, 3, 6, 9, 12) or in the community / home with community health workers (months 2, 5, 8). All visits will include BP measurement, lifestyle counseling, adherence encouragement, and assessment of adverse events. The GHESKIO visits will also include a physical exam. Participants in the early intervention arm will receive monthly amlodipine refills. Participants in the SOC arm will initiate amlodipine only if they develop hypertension (SBP >140 or DBP >90 mm Hg).

At the 12-month study visit, participants will also complete a brief questionnaire about changes in health behaviors and have viral load measured. Participants may return to the HIV clinic at any time for symptoms, questions, or other concerns, and a BP measurement will be taken at each of these encounters. Adverse events will be assessed at each visit. Medical record abstraction will be done by research staff for any hospitalization or death among a participant.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 250 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Treatment of Early Hypertension Among Persons Living With HIV in Haiti
• Actual Study Start Date: February 26, 2021
• Estimated Primary Completion Date: February 2023
• Estimated Study Completion Date: February 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Intervention (Early hypertension); Participants randomized to the early HTN treatment arm will initiate 5mg daily of amlodipine immediately, increasing to 10 mg if SBP >130 mmHg after 1 month.	Drug: Amlodipine 5mg; Amlodipine, Haiti's first-line antihypertensive medication, will be administered to the intervention group.; Other Name: Norvasc
No Intervention: Standard of Care; Participants randomized to the SOC arm will not be initiated on any medications initially. They may be initiated on amlodipine only if they develop HTN (SBP ≥140 or DBP ≥90 mm Hg).

Outcome Measures

Primary Outcome Measures :

1. Difference in change of mean systolic blood pressure (SBP) between study arms [ Time Frame: Baseline, 12 months ]
   Difference in change of mean systolic blood pressure (SBP) between intervention and control arms

Secondary Outcome Measures :

1. Change in number of participants with HIV viral suppression as measured by HIV-1 RNA viral loads < 1,000 copies/mL [ Time Frame: Baseline, 12 months ]
   Change in number of participants with HIV viral suppression as measured by HIV-1 RNA viral loads < 1,000 copies/mL
2. Change in HIV medication adherence as measured by number of participants with > 90% adherence using 4-day pill recalls [ Time Frame: Baseline, 6 months and 12 months ]
   Change in HIV medication adherence as measured by number of participants with > 90% adherence using 4-day pill recalls
3. Adverse Events [ Time Frame: Followup month 1 ]
   Number of subjects who have adverse events related to amlodipine, including dizziness, fainting, lower extremity edema, and any other symptoms which may be related. Symptoms will be categorized according to the Division of AIDS (DAIDS) severity score, with Grade III-IV considered adverse events.
4. Adverse Events [ Time Frame: Followup month 2 ]
   Number of subjects who have adverse events related to amlodipine, including dizziness, fainting, lower extremity edema, and any other symptoms which may be related. Symptoms will be categorized according to the Division of AIDS (DAIDS) severity score, with Grade III-IV considered adverse events.
5. Adverse Events [ Time Frame: Followup month 3 ]
   Number of subjects who have adverse events related to amlodipine, including dizziness, fainting, lower extremity edema, and any other symptoms which may be related. Symptoms will be categorized according to the Division of AIDS (DAIDS) severity score, with Grade III-IV considered adverse events.
6. Adverse Events [ Time Frame: Followup month 5 ]
   Number of subjects who have adverse events related to amlodipine, including dizziness, fainting, lower extremity edema, and any other symptoms which may be related. Symptoms will be categorized according to the Division of AIDS (DAIDS) severity score, with Grade III-IV considered adverse events.
7. Adverse Events [ Time Frame: Followup month 6 ]
   Number of subjects who have adverse events related to amlodipine, including dizziness, fainting, lower extremity edema, and any other symptoms which may be related. Symptoms will be categorized according to the Division of AIDS (DAIDS) severity score, with Grade III-IV considered adverse events.
8. Adverse Events [ Time Frame: Followup month 8 ]
   Number of subjects who have adverse events related to amlodipine, including dizziness, fainting, lower extremity edema, and any other symptoms which may be related. Symptoms will be categorized according to the Division of AIDS (DAIDS) severity score, with Grade III-IV considered adverse events.
9. Adverse Events [ Time Frame: Followup month 9 ]
   Number of subjects who have adverse events related to amlodipine, including dizziness, fainting, lower extremity edema, and any other symptoms which may be related. Symptoms will be categorized according to the Division of AIDS (DAIDS) severity score, with Grade III-IV considered adverse events.
10. Adverse Events [ Time Frame: Followup month 12 ]
    Number of subjects who have adverse events related to amlodipine, including dizziness, fainting, lower extremity edema, and any other symptoms which may be related. Symptoms will be categorized according to the Division of AIDS (DAIDS) severity score, with Grade III-IV considered adverse events.
11. Acceptability assessed by change in percent of participants at baseline and retained at 12 months [ Time Frame: Baseline, 12 months ]
    Percent of participants who are enrolled at baseline and remain in the study by 12 months
12. Acceptability of study intervention assessed by qualitative interviews among participants and providers [ Time Frame: 12 months ]
    Using semi-structured interview guides exploring topics including acceptability, side effects, perceived benefit, and perceived cost, in depth interviews will be conducted with 15-20 study participants in the intervention arm, and all healthcare providers involved in the study (nurses, doctors, social workers).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• PLWH 18-65 years of age
• ART duration ≥ 1 year, stable regimen ≥ 6 months
• HIV 1-RNA < 1,000 copies/mL within past 12 months
• Pre-HTN (SBP 120-139 or DBP 80-89 mm Hg)
• No current antihypertensive treatment
• Receives HIV care at GHESKIO
• Willing to provide consent

Exclusion Criteria:

• Pregnancy
• Kidney disease or diabetes
• On protease inhibitor/ritonavir
• Advanced illness with limited life expectancy
• Plans to move out of the area within the next year
• Clinician determination that patient is unstable on ART

Contacts and Locations

Contacts

Contact: Margaret McNairy, MD; 646-831-2156; mam9365@med.cornell.edu

Locations

Haiti

GHESKIO; Recruiting

Port-au-Prince, Haiti

Contact: Vanessa Rouzier, MD vrouzier@gheskio.org

Sponsors and Collaborators

Weill Medical College of Cornell University

Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic

Fogarty International Center of the National Institute of Health

Investigators

• Principal Investigator: Margaret McNairy, MD; Weill Medical College of Cornell University
• Principal Investigator: Jean Pape; Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Yan LD, Rouzier V, Dade E, Guiteau C, Pierre JL, St-Preux S, Metz M, Oparil S, Pape JW, McNairy M. Treatment of early hypertension among persons living with HIV in Haiti: Protocol for a randomized controlled trial. PLoS One. 2021 Aug 5;16(8):e0254740. doi: 10.1371/journal.pone.0254740. eCollection 2021.

• Responsible Party: Weill Medical College of Cornell University
• ClinicalTrials.gov Identifier: NCT04692467
• Other Study ID Numbers: 20-03021735; R21TW011693 ( U.S. NIH Grant/Contract )
• First Posted: December 31, 2020
• Last Update Posted: December 21, 2021
• Last Verified: December 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: All the individual participant data collected during the trial, after deidentification will be shared.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP)
• Time Frame: Study protocol and statistical analysis plan available after publication and ending 3 years following publication.
• Access Criteria: Researchers who provide a methodologically sound proposal may have access. Proposals should be directed to the PI at mam9365@med.cornell.edu. To gain access, data requestors will need to sign a data access agreement. Data are available following publications through 3 years after publication and will be provided directly from the PI.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Weill Medical College of Cornell University:

hypertension; HIV

Additional relevant MeSH terms:

Hypertension; Prehypertension; Vascular Diseases; Cardiovascular Diseases; Amlodipine; Antihypertensive Agents; Calcium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Vasodilator Agents