A Series of N-of-1 Randomised, Adaptive, Blinded, Placebo-Controlled Trials of Overnight In-Bedroom Air Filtration as Adjuvant Treatment in Reducing Inflammatory Biomarkers Among Survivors of Adult-Onset Cancer With Elevated C-Reactive Protein
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 5
- 主要终点
- C-reactive protein (CRP)
研究概览
简要总结
The BREATHS trial aims to investigate whether overnight in-bedroom air filtration reduces inflammation and cardiac biomarkers in adult survivors of cancer who are at high risk for cardiovascular complications.
The study consists of individualized experiments (N-of-1 trials) conducted in the home settings of adults residing in densely populated urban areas with the most severe air quality levels in Valencia, Spain, where fine particulate matter (PM2.5) and nitrogen dioxide levels exceed the limits set by the World Health Organization (WHO) and EU Directive.
Participants will be exposed to 3 treatment sets (blinded phase), each consisting of a 14-day period of filtered air using a portable air filtration unit ("true-HyperHepa) and a 14-day period of unfiltered air (using the same portable unit with "sham filters"). The intervention will be administered nightly for a minimum of 7 consecutive hours and will last between 4 and 12 weeks for each participant, contingent upon the demonstration of clinical benefit, defined by a reduction in the levels of the blood biomarker C-reactive protein. An unblinded phase will be implemented for participants who do not experience a clinically meaningful change in CRP. During this phase, they will undergo a 14-day period without treatment, followed by 14-day period of both nightly and daily filtered air therapy.
The primary endpoint of this study is defined as the change in blood concentrations of CRP. The secondary endpoints include the changes in levels of three other noninvasive blood biomarkers associated with inflammation and cardiovascular health, and blood pressure.
Both indoor and outdoor fine particulate matter (PM2.5) exposure concentrations will be continuously monitored in the study.
详细描述
Background. Inflammation, a common result of anticancer therapies, correlates with poor survival and cardiovascular issues in cancer survivors. High levels of C-reactive protein (CRP), D-dimer, and serum amyloid A (SAA) indicate cancer recurrence, mortality, and cardiotoxicity. CRP-lowering clinical trials have proven that the magnitude of the reduction in cardiac events in patients with residual inflammatory risk is directly proportional to the achieved reduction in CRP, with the greatest benefit in those achieving a threshold below than 2 milligrams per litre (mg/L).
Cancer survivors may benefit from non-pharmacological anti-inflammatory treatments that do not exacerbate cardiotoxicity burden. Evidence suggests the air purifiers lower inflammatory biomarkers in high-risk cardiovascular groups. Air filtration presents a promising alternative to inflammation-inhibiting drugs, but its anti-inflammatory and cardioprotective effects in cancer survivors and interactions with medications remain unclear.
Design, setting and participants. A series of N-of-1 randomised, adaptive, blinded, placebo-controlled trials will be conducted at the home sitting of community-dwelling cancer survivors who are registered in primary care practices of the city of Valencia, Spain. Participants eligible are aged 18 years or older, have a history of breast, colorectal, prostate, lung and haematologic cancer, completed curative cancer treatment with evidence of remission and screened blood CRP level of at least 3 mg/L (within individual SD CRP of ~0.20 mg/L at baseline is accepted).
Screening for CRP levels. Up to two home visits could be carried out to collect a 5 microlitres (µl) blood microsample and analyse the CRP levels in real-time of the potentially eligible participants. These screening visits will be done no more than 28 and 7 days prior to blinded N-of-1 phase, respectively.
Recruitment. Participants will be identified via 3 strategies: advertisements on social media, snowball sampling and in-primary care clinics referrals. Staff from local primary care setting participating in the study will identify eligible potentially participant. The selection criteria for primary care settings were based on neighborhood air quality, specifically urban areas with the highest index impact of pollutant on population > 125 and NO2 levels exceeding WHO and EU Directive 2008/50/EC limits: Malilla, Russafa, and Arrancapins.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
The sequence allocation will be masked for the participants, general practitioners, primary care staff and research team members, except for the field researcher to dispense the correct treatment.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult-onset cancer survivors with a diagnosis of breast, colon, colorectum, rectum, prostate, non-small lung, Hodgkin lymphoma, non-Hodgkin lymphoma, chronic lymphoid leukaemia and chronic myeloid leukaemia cancer.
- •Aged ≥ 18 years at cancer diagnosis -upper age limit to study entry = 75 years.
- •People of both genders, all racial and ethnic backgrounds.
- •Non-smokers (i.e., not smoking during previous 12 months).
- •A history of local, regional or distant recurrence, primary second cancers or multiple primary tumours will be not reasons to exclude.
- •No previous evidence for metastatic disease.
- •Evidence of complete remission defined as a decrease in or disappearance of signs and symptoms of cancer after treatment.
- •Having completed definitive treatment (surgery, neoadjuvant/adjuvant cytotoxic chemotherapy, radiotherapy, immunotherapy) at least 12 months.
- •Continuous, maintenance therapy is considered if initiated ≥3 months prior to study treatment and prescribed for long-term, chronic use without interruption during the trial, or completed for at least ≥3 months before starting the trial.
- •Having a high inflammatory cardiac risk profile at the initial screening defined as a CRP measurement ≥ 3 to < 10 mg/L, or ≥ 10 mg/L if acute inflammation is ruled out.
- •Having stable hypertension (if applicable): no medication changes in prior 30 days, systolic BP <160 mm Hg and either ≥ 130 mm Hg without antihypertensive medications, or diagnosis of hypertension in medical records.
- •Clinical evidence of cardiovascular, respiratory and/or musculoskeletal disease, and/or other controlled and stable chronic medical conditions will not be reason of exclusion.
- •Any medical prescription(s) if routinely administered and continued through the trial period.
- •Living at one of the urban areas of the city of Valencia with the highest index impact of pollutant on population values (IIPP > 125): Russafa, Malilla and Arrancapins neighbourhoods.
- •Permanent residence in their usual home at least 3 months prior to the first collected blood sample in the first cycle and without plans to move out toward another dwelling during the trial study.
- •Living in a non-smoking household.
- •Internet connection (Wi-Fi) in the house.
- •Signed informed consent prior to commencement of specific protocol procedures.
排除标准
- •Recently diagnosed with cancer or plans for additional cancer therapy and/or surgery during the trial period.
- •Metastatic disease.
- •Planned medication prescription to start during the trial.
- •Current chronic anti-inflammatory drug prescriptions or other chronic drugs (e.g., antihypertensive drugs) will be no reason for exclusion if its use is continued for the duration of the trial period.
- •Having uncontrolled hypertension: participants with average systolic BP >160 mmHg over any 10-day period prior and during the study.
- •History of uncontrolled, unstable chronic disease as defined by clinical practice guidelines and documented in medical records - within past 6 months to screening visit(s) and during the study (i.e., uncontrolled diabetes mellitus). Psychiatric illness that would limit compliance with trial requirements and/or prevent the patient from giving informed consent.
- •History of ongoing, chronic or recurrent infectious disease, and having suspected or proven immunocompromised state (i.e., Human Immunodeficiency Virus infection).
- •Self-report of alcohol or substance abuse within the past 12 months, including at-risk drinking (current consumption of more than 14 alcoholic drinks per week).
- •Shift workers or subjects who have the work schedule falling outside the hours of 07:00 a.m. and 10:00 p.m.
- •Plans to move out of usual home during the trial period.
- •Unwilling to spend at least 7-h/overnight in the bedroom.
- •Pre-existing an air filtration system that improve household air quality. If so, the device will be disconnected during all the trial cycles.
- •Unwilling to give consent.
- •Additional inclusion criteria (non-exclusive; when CRP test is unavailable in medical records) associated with high or very high cardiovascular (CV) toxicity risk factors (according to the European Society of Cardiology guidelines on Cardio-Oncology):
- •High or very high baseline CV toxicity risk pre-treatment (HFA-ICOS risk stratification score); risk factors including:
- •Prior history of CV disease (e.g., coronary artery disease).
- •Presence of multiple CV-risk factors (e.g., hypertension, dyslipidemia).
- •Current or concomitant cancer treatment.
- •Prior cardiotoxic cancer therapy (e.g., anthracycline, radiotherapy to left chest).
- •Lifestyle risk factors (history of smoking, body mass index >30).
- •Specific cardiotoxic cancer therapies with a high risk of long-term CV complications (any of these):
- •Total lifetime cumulative dose anthracycline ≥ 250 mg/m2 doxorubicin equivalent.
- •High-dose anthracycline ≥ 250 mg/m2 doxorubicin equivalent.
- •High-dose RT > 15 Gray (Gy) Mean Heart Dose (MHD).
- •Anthracycline ≥ 100 mg/m2 doxorubicin equivalent in combination with radiotherapy 5-15 Gy MHD.
- •Multitargeted tyrosine kinase inhibitors (TKI) targeting BCR-ABL and concomitant high-dose dexamethasone therapy >160 mg/month.
- •Combination of RAF and MEK inhibition.
- •Single-agent immune checkpoints inhibitors (ICI) therapy followed by previous cardiotoxic cancer therapies: RT, anthracyclines, 5-fluorouracil, and TKI.
- •Combination of two types of ICI (anti-PD1, e.g., nivolumab and anti-CTLA-4, e.g., ipilimumab).
- •Moderate or severe cancer therapy-related CV toxicity detected during cancer treatment or new CV symptomatic/asymptomatic abnormalities at the end of cancer treatment (3 or 12 months after therapy).
研究组 & 干预措施
Air purifier nightly
Participants are exposed to filtered air (HyperHEPA filter) nightly in the bedroom, in 14-day periods, up to 3 treatment sets in 12 weeks (blinded phase).
The blinded N-of-1 trial will last between 4 and 12 weeks per participant, depending on the treatment set(s) received (cycle 1, 2 and 3) to produce evidence of clinical benefit (CRP < 2 mg/L or CRP reductions ≥ 35%).
干预措施: High efficiency particulate air filtration system (nightly administration) (Device)
Sham air filter
Participants receive an intervention of sham air purifiers nightly in the bedroom, in 14-day periods, up to 3 treatment sets in 12 weeks (blinded phase). The blinded N-of-1 trial will last between 4 and 12 weeks per participant, depending on the treatment set(s) received (cycle 1, 2 and 3) to produce evidence of clinical benefit (CRP < 2 mg/L or CRP reductions ≥ 35%).
干预措施: Air filtration system without filters (sham) (Device)
Air purifier nightly and daily
Participants are exposed to nightly and daily filtered air (HyperHEPA filter) in the bedrooms (open-label phase). The air purifier with active filter is continuously operated (24 hours for 14 days). Participants who do not achieve the clinically meaningful change established in the trial (CRP < 2 mg/L or CRP reductions ≥ 35%) after the treatment set 3 (cycle 3) will take this open-label phase.
干预措施: High efficiency particulate air filtration system (nightly and daily administration) (Device)
No treatment
14-day period of no intervention. Participants who do not achieve the clinically meaningful change established in the trial (CRP < 2 mg/L or CRP reductions ≥ 35%) after the treatment set 3 (cycle 3) will take this open-label phase.
结局指标
主要结局
C-reactive protein (CRP)
时间窗: At baseline and in the day 7 and 14 of each period. In the same time interval in the morning (between 07:00-10:00 am).
The primary outcome is the change in blood CRP concentrations. A portable point-of-care testing via capillary finger-prick microsampling will be used to measure the blood levels of CRP (5µl per participant once a week; measuring range, 0.48-200 mg/L).
次要结局
- D-dimer(At baseline and in the day 7 and 14 of each period. In the same time interval in the morning (between 07:00-10:00 am).)
- Serum Amyloid A (SAA)(At baseline and in the day 7 and 14 of each period. In the same time interval in the morning (between 07:00-10:00 am).)
- Haemoglobin A1c (Hb1Ac)(At baseline and in the day 7 and 14 of each period. In the same time interval in the morning (between 07:00-10:00 am).)
- Systolic and diastolic blood pressure (BP)(At baseline and in the day 7 and 14 of each period. In the same time interval in the morning (between 07:00-10:00 am) and before the blood collection and any medication and in a fasting condition.)