Personalised health education against health damage of COVID-19 epidemic in the elderly Hungarian population (PROACTIVE-19): protocol of an adaptive randomised controlled clinical trial

Background Early reports indicate that COVID-19 may require intensive care unit (ICU) admission in 5–26% and overall mortality can rise to 11% of the recognised cases, particularly affecting the elderly. There is a lack of evidence-based targeted pharmacological therapy for its prevention and treatment. We aim to compare the effects of a World Health Organization recommendation-based education and a personalised complex preventive lifestyle intervention package (based on the same WHO recommendation) on the outcomes of the COVID-19. Methods PROACTIVE-19 is a pragmatic, randomised controlled clinical trial with adaptive “sample size re-estimation” design. Hungarian population over the age of 60 years without confirmed COVID-19 will be approached to participate in a telephone health assessment and lifestyle counselling voluntarily. Volunteers will be randomised into two groups: (A) general health education and (B) personalised health education. Participants will go through questioning and recommendation in 5 fields: (1) mental health, (2) smoking habits, (3) physical activity, (4) dietary habits, and (5) alcohol consumption. Both groups A and B will receive the same line of questioning to assess habits concerning these topics. Assessment will be done weekly during the first month, every second week in the second month, then monthly. The composite primary endpoint will include the rate of ICU admission, hospital admission (longer than 48 h), and mortality in COVID-19-positive cases. The estimated sample size is 3788 subjects per study arm. The planned duration of the follow-up is a minimum of 1 year. Discussion These interventions may boost the body’s cardiovascular and pulmonary reserve capacities, leading to improved resistance against the damage caused by COVID-19. Consequently, lifestyle changes can reduce the incidence of life-threatening conditions and attenuate the detrimental effects of the pandemic seriously affecting the older population. Trial registration The study has been approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (IV/2428- 2 /2020/EKU) and has been registered at clinicaltrials.gov (NCT04321928) on 25 March 2020.


Stay smoke-free
"To our knowledge, among the lifestyle factors, tobacco smoking has the greatest impact on the outcome of coronavirus cases. The course of upper airway infections is milder in non-smokers. Accordingly, we can highly recommend that you stop smoking as soon as possible. If you are unable to do this, you might cut down smoking at least. If you need any further support to quit smoking, please let us know now." If yes: "To get help with quitting, call 06-80-44-20-44, which is a free service." "Very good, keep it up, and stay smoke-free! The course of upper airway infections is milder in non-smokers."

Stop smoking
First call Physical activity "The most common complication of the coronavirus infection are lung and heart disease, which has a major impact on the need for intensive care. If you perform enough physical activity, it can protect you from complications. Being in your home for long periods of time and because of this moving less can be a danger. We also advise you to avoid contact with others during physical activity as this may increase the risk of infection. " "Your physical activity is less than the recommended 150 minutes per week. We recommend the following physical activities: leisure physical activity, commuting to work: walking or cycling, physical activity during work, housework, sports or planned physical activity. All activities should be performed in bouts of at least 10 minutes duration, with the recommended weekly duration being at least 3 * 50 or 5 * 30 minutes. If possible, stand up and move for 10 minutes after each hour spent sitting." "Your physical activity is below the recommended 150 minutes per week, possibly increase it to over 150 minutes per week. For more detailed advice please contact your physician." "Your regular physical activity reaches the recommended level, if possible, you can increase it to over 300 minutes a week. If possible, stand up and move for 10 minutes after each hour spent sitting." "Your regular physical activity reaches the maximum recommended, and it is advisable to keep it at that level. If possible, stand up and move for 10 minutes after each hour spent sitting." X next to answer. If yes, UNHEALTHY "Do you, on an average day consume any of the following products: soft drinks, pre-packaged snacks (such as frozen pizza and cookies), chocolate or fast food?" "What is your current weight? What is your current height?" Enter weight and height into computer. The computer will automatically generate BMI.
"How many and what kind of fruits do you consume on an average day? How many and what kind of vegetables do you consume on an average day?" (One portion is 150 grams (one apple / banana, one glass of freshly squeezed juice, one medium tomato)) X next to answer. If beef -pork -lamb -game or can't decide= UNHEALTHY If any of the index questions is UNHEALTHY, Dietary recommendation (±BMI recommendation based on BMI) "Do you consume meat? What kind of meats do you consume more frequently: fishpoultry / beef -pork -lamb-game/ can't decide" "We'd like to bring to your attention that an overly low or an overly high body weight poses an increased risk in terms of severity in every disease; thus, in the case of coronavirus, a more severe disease course is more likely to occur. Similarly, unhealthy dietary habits can negatively affect various factors including for example the risk of cardiovascular complications. With the current situation -leading to greater time being spent at home -the probability of gaining weight and taking to unhealthy dietary habits is higher." (To the operator: The part where the index questions detected unhealthy consumption should be highlighted for the individuals.) "We advise that you regularly consume fruits, vegetables, legumes (e.g., beans, peas, lentils), unsalted nuts and whole grain products (such as millet, oats, wheat and brown rice). You should consume at least 400 grams of vegetables and fruits every day (excluding potatoes!). Free sugars usually present in soft drinks and sweets are better avoided. Avoid consuming fatty foods, fat intake should amount for less than third of your daily calorie intake. Products containing unsaturated fats such as fish, nuts, sunflower-and olive oil are preferred, you should limit products containing saturated fats (such as fatty meat, cream and cheese) and you should avoid products containing trans-fats or additive such as some pastries and frozen foods, pre-packed snacks (crisps, cookies), fast-food items, cow meat." "Naturally, if you are receiving dietary advice from a medical professional for health-related reasons, we recommend strict compliance with those recommendations." "Compared to your body height, your body weight is ideal with regard to the risk of viral infection."

Beginning sentences for every participant
Positive feedback BMI <18.5: "Additionally, as your body weight is lower than the optimal range for your height, we recommend that you increase your consumption as possible." BMI ≥30: "Additionally, as your body weight exceeds the optimal range for your height, we recommend that you decrease your consumption. It is important that this limitation is not extreme, because it could also pose a threat to your health and safety. We recommend 0.5-1 kg / week weight loss as a target." "Your dietary habits, as assessed by our questions, follow a healthy pattern. Still, we would like to inform you on the concepts of a healthy diet: that you regularly consume fruits, vegetables, legumes (e.g., beans, peas, lentils), unsalted nuts, and whole grain products (such as millet, oats, wheat and brown rice). You should consume at least 400 grams of vegetables and fruits every day (excluding potatoes!). Free sugars usually present in soft drinks and sweets are better avoided. Avoid consuming fatty foods, fat intake should amount for less than third of your daily calorie intake. Products containing unsaturated fats such as fish, nuts, sunflower-and olive oil are preferred, you should limit products containing saturated fats (such as fatty meat, cream and cheese) and you should avoid products containing trans-fats or additive such as some pastries and frozen foods, pre-packed snacks (crisps, cookies), fast-food items, cow meat."

First call Alcohol consumption
English protocol Do you drink (alcohol)?
1. For how long? How often do you drink alcohol?
Have you consumed alcohol regularly in the past?

Guidance 1 Guidance 3
Guidance 2 Once a week or more frequently Less than once a week (To the operator: highlight what she/he consumes based on self-declaration). "There are two very important things to know about alcohol consumption: Alcohol consumption is harmful, and it does not protect against the coronavirus." I advise you to consume as little alcohol as possible and do not exceed the following quantities: -for men: 3 dL of wine or 3 glasses of beer or 6 cL hard drink -for women: 2 dL of wine or 2 glasses of beer or 4 cL hard drink or 2 cocktails Furthermore, do not consume more than 4 dL of wine or 4 glasses of beer or 8 cL of hard drink per occasion. The best thing you can do for your health is if you do not drink alcohol at all." "There are two very important things to know about alcohol consumption: alcohol consumption is harmful, and it does not protect against the coronavirus. Keep in mind, that you should not consume more than 4 dL of wine or 4 glasses of beer or 8 cL of hard drink per occasion. The best thing you can do for your health is if you do not drink alcohol at all." "You're doing great. Keep it up! Alcohol consumption has detrimental effects on health and does NOT protect you from coronavirus, we advise that keep alcohol-free!" Intervention "As much as your opportunities allow, keep up your social connections, stay in touch with your family, friends, and acquaintances. If because of coronavirus related regulations you are required to avoid physical contact with others, try maintaining your social connections through other platforms, e.g. telephone, e-mail, social media (Facebook, TikTok, Skype, Twitter, etc.).

Group B Decision tree -1st call
Establish a daily rhythm! Pay attention to your own needs and feelings. Engage in activities that you like and that make you feel calm, for example: watching movies or reading.
Share your thoughts with others! At the same time, you also should pay attention to the ones around you, listen to them, encourage them to share their experiences and feelings.
Constantly following news related to the epidemic can make you feel overwhelmed. Do not constantly follow this news, only periodically! Try to avoid all information that is not coming from a reliable source. You should primarily rely on news coming from healthcare professionals, for example the governmental information page: https://koronavirus.gov.hu/. Or dial any of the following informational lines: (06 80 277 455 / 06 80 277 456).
Because of the coronavirus related regulations, our social interactions can become limited easily, anybody can feel alone in a situation like this.
If you are feeling very alone, please let us know, and we can provide you a phone number that you can call to get professional help. (If the participant ask for the phone number: Magyar Elsősegély Lelki Szolgálat: 116-123.)"