Does Rosuvastatin Delay Progression of Atherosclerosis in HIV

• Sponsor: Bayside Health (Other)
• Overall Status: Completed
• CT.gov ID: NCT01813357
• Collaborator: (none)
• Enrollment: 84
• Locations: 2
• Arms: 2
• Actual Duration (Months): 64
• Patients Per Site: 42
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

This study is a randomised double blind placebo controlled trial comparing Rosuvastatin with placebo in HIV positive people who are at intermediate cardiovascular risk.

It is possible that HIV positive people will receive a greater benefit from statins because of their higher baseline levels of inflammation. Current Australian guidelines recommend initiation of statin therapy on the basis of cholesterol level and the presence of other risk factors for heart disease (such as diabetes) but do not take into account whether a patient is infected with HIV. This study aims to determine what benefit HIV infected people will receive from starting statin therapy earlier then currently recommended.

Condition or Disease	Intervention/Treatment	Phase
HIV; Cardiovascular Disease	Drug: Rosuvastatin; Other: Placebo	Phase 4

Detailed Description

Participants will be randomised to receive either the active agent (Rosuvastatin) or a placebo once daily for 96 weeks.

Participants will undergo blood tests and ultrasounds of the arteries of the neck (carotid intima media thickness) prior to starting Rosuvastatin and then after 1 and 2 years on the drug to determine what effect it has on markers of inflammation, cholesterol levels and thickness of blood vessels.

Study Design

• Study Type: Interventional
• Actual Enrollment: 84 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Does Rosuvastatin Delay Progression of Atherosclerosis in People With HIV Infection at Moderate Cardiovascular Risk? A Multicentre Randomized, Double Blind Placebo-controlled Trial
• Actual Study Start Date: Jul 2, 2013
• Actual Primary Completion Date: May 17, 2018
• Actual Study Completion Date: Nov 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo sugar pill that is encapsulated so as to appear identical to the active agent	Other: Placebo; Placebo arm included to maintain blinding; Other Names: Sugar Pill
Experimental: Rosuvastatin Rosuvastatin 20mg daily	Drug: Rosuvastatin; encapsulated tablet 20mg daily; Other Names: Brand name: Crestor

Outcome Measures

Primary Outcome Measures

1. Progression of Carotid Intima Media Thickness [Baseline to week 96]

   Carotid intima media thickness will be measured by ultrasonography and the change from baseline to week 96 calculated

Secondary Outcome Measures

1. Rates of Adverse Events [Will be assessed every 12 weeks and formally reported at 96 weeks of followup]

   Number of participants with adverse events in total and also the number of participants with adverse events thought secondary to the study medication

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 100 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age ≥ 18 years

• Moderate cardiovascular disease (CVD) risk, (10-15% 10 year risk of CVD)

• HIV positive

• Stable combination anti-retroviral therapy (cART) with plasma HIV viral load <200copies/ml for ≥ 6 months

Exclusion Criteria:

• Recommended use of lipid lowering therapy according to Australian guidelines

• Prior use of statin, fibrate, ezetimibe within the last six months

• Contraindication to statin use

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alfred Hospital	Melbourne	Victoria	Australia	3004
2	Hospitaux Universitaires de Geneve	Geneve		Switzerland

Sponsors and Collaborators

• Bayside Health

Investigators

• Principal Investigator: Jennifer Hoy, Alfred health, Monash University

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Feb 14, 2014

More Information

Publications

None provided.

• Responsible Party: Bayside Health
• ClinicalTrials.gov Identifier: NCT01813357
• Other Study ID Numbers: AH-491/12; ACTRN12612001082897
• First Posted: Mar 19, 2013
• Last Update Posted: Aug 28, 2020
• Last Verified: Aug 1, 2020

• Keywords provided by Bayside Health: HIV; Cardiovascular disease; Inflammation; Statin
• Additional relevant MeSH terms: Cardiovascular Diseases; Atherosclerosis; Rosuvastatin Calcium

Study Results

Participant Flow

Arm/Group Title	Placebo	Rosuvastatin
Arm/Group Description	sugar pill that is encapsulated so as to appear identical to the active agent Placebo: Placebo arm included to maintain blinding	Rosuvastatin 20mg daily Rosuvastatin: encapsulated tablet 20mg daily
Period Title: Overall Study
STARTED	40	44
COMPLETED	35	38
NOT COMPLETED	5	6

Baseline Characteristics

Arm/Group Title	Placebo	Active	Total
Arm/Group Description	Participants received daily placebo	Participants received daily rosuvastatin	Total of all reporting groups
Overall Participants	40	44	84
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.4 (6.4)	53.9 (5.9)	54.1 (6.3)
Sex: Female, Male (Count of Participants)
Female	0 0%	2 4.5%	2 2.4%
Male	40 100%	42 95.5%	82 97.6%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
Australia	27 67.5%	28 63.6%	55 65.5%
Switzerland	13 32.5%	16 36.4%	29 34.5%
Current Smoker (Count of Participants)
Count of Participants [Participants]	12 30%	16 36.4%	28 33.3%
Total cholesterol (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	5.3 (1.1)	5.4 (0.8)	5.3 (1.0)
Duration HIV infection (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	13.6 (7.7)	17.2 (8.5)	16 (7.9)
Current cluster of differentiation of 4 (CD4) Cell count (cells/ul) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cells/ul]	550 (254)	693 (259)	590 (250)

Outcome Measures

1. Primary Outcome

Title	Progression of Carotid Intima Media Thickness
Description	Carotid intima media thickness will be measured by ultrasonography and the change from baseline to week 96 calculated
Time Frame	Baseline to week 96

Outcome Measure Data

Analysis Population Description

Intention to treat

Arm/Group Title	Placebo	Rosuvastatin
Arm/Group Description	sugar pill that is encapsulated so as to appear identical to the active agent Placebo: Placebo arm included to maintain blinding	Rosuvastatin 20mg daily Rosuvastatin: encapsulated tablet 20mg daily
Measure Participants	40	44
Mean (Standard Error) [mm]	0.0062 (0.0039)	0.004 (0.0036)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Rosuvastatin
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.684
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.002
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Rates of Adverse Events
Description	Number of participants with adverse events in total and also the number of participants with adverse events thought secondary to the study medication
Time Frame	Will be assessed every 12 weeks and formally reported at 96 weeks of followup

Outcome Measure Data

Analysis Population Description

Intention to treat population

Arm/Group Title	Placebo	Rosuvastatin
Arm/Group Description	sugar pill that is encapsulated so as to appear identical to the active agent Placebo: Placebo arm included to maintain blinding	Rosuvastatin 20mg daily Rosuvastatin: encapsulated tablet 20mg daily
Measure Participants	40	44
Count of Participants [Participants]	22 55%	35 79.5%

Adverse Events

Time Frame	Adverse event (AE) data was collected during study involvement and for 144 weeks post completion of last study visit (up to 240 weeks).
Adverse Event Reporting Description	Standard definitions used
Arm/Group Title	Placebo		Rosuvastatin
Arm/Group Description	sugar pill that is encapsulated so as to appear identical to the active agent Placebo: Placebo arm included to maintain blinding		Rosuvastatin 20mg daily Rosuvastatin: encapsulated tablet 20mg daily
All Cause Mortality
	Placebo		Rosuvastatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0%)		1/44 (2.3%)
Serious Adverse Events
	Placebo		Rosuvastatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/40 (15%)		7/44 (15.9%)
Cardiac disorders
Acute myocardial infarction	1/40 (2.5%)	1	2/44 (4.5%)	2
Heart Failure	0/40 (0%)	0	1/44 (2.3%)	1
Endocrine disorders
Type two diabetes	0/40 (0%)	0	2/44 (4.5%)	2
Gastrointestinal disorders
Oesophageal Malignancy	1/40 (2.5%)	1	0/44 (0%)	0
Haemoptysis	1/40 (2.5%)	1	0/44 (0%)	0
Hepatobiliary disorders
Elevated Alanine aminotransferase (ALT)	1/40 (2.5%)	1	1/44 (2.3%)	1
Musculoskeletal and connective tissue disorders
elevated creatinine kinase	0/40 (0%)	0	1/44 (2.3%)	1
Lumbar vertebral disc herniation	1/40 (2.5%)	1	0/44 (0%)	0
Nervous system disorders
Stroke	0/40 (0%)	0	1/44 (2.3%)	1
Vascular disorders
Hypertension	0/40 (0%)	0	1/44 (2.3%)	1
Acute Mesentric Ischaemia	1/40 (2.5%)	1	0/44 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		Rosuvastatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/40 (72.5%)		36/44 (81.8%)
Cardiac disorders
Hypertension	11/40 (27.5%)	11	13/44 (29.5%)	13
Gastrointestinal disorders
Non-specific gastrointestinal disturbance	4/40 (10%)	4	5/44 (11.4%)	5
Hepatobiliary disorders
ALT elevation	4/40 (10%)	4	13/44 (29.5%)	13
Musculoskeletal and connective tissue disorders
Myalgia	7/40 (17.5%)	7	1/44 (2.3%)	1
CK elevation	3/40 (7.5%)	3	4/44 (9.1%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.