Trial Outcomes & Findings for Fermented Soybean Supplementation Among Active Pulmonary Tuberculosis Patients With Standard Therapy in Indonesia (NCT NCT02554318)

Last Updated: 2022-06-21

Results Overview

Change of body weight of the participants over the two months intervention period as measured on a kilograms scale. The change was calculated from two-time points as the value at the later time point minus the value at the earlier time point. Positive numbers represent increases and negative numbers represent decreases. A higher value score in change means a better outcome on nutritional status for the patients after the study.

Recruitment status

COMPLETED

Study phase

Target enrollment

147 participants

Primary outcome timeframe

Baseline, 2 months

Results posted on

2022-06-21

Participant Flow

Between November 2013 and February 2015, patients who attended the lung clinics in Surabaya for newly diagnosed pulmonary TB were screened for study enrollment.

After the enrollment of the study, several participants withdrew their assignment due to several reasons such as underlying disease, heavy smoker, they did not stay in the city, plan to move to other city, and dislike the food.

Participant milestones

Participant milestones
Measure	Intervention TB standard therapy with fixed dose combination : once per day by mouth for 2 months Fixed dose combination = RHZE (150mg/75mg/400mg/275mg) R=rifampicin, H=isoniazid, Z=pyrazinamide, E=ethambutol, Patients with body weight: 30 - 37 kg = 2 tablets, 38 - 54 kg = 3 tablets, 55 - 70 kg = 4 tablets, and ≥71 kg = 5 tablets and 166.5 grams cooked fermented soybean (tempeh) daily for two months Rifampicin Isoniazid Pyrazinamide Ethambutol Fermented soybean	Control TB standard therapy with fixed dose combination : once per day by mouth for 2 months Fixed dose combination = RHZE (150mg/75mg/400mg/275mg) R=rifampicin, H=isoniazid, Z=pyrazinamide, E=ethambutol, Patients with body weight: 30 - 37 kg = 2 tablets, 38 - 54 kg = 3 tablets, 55 - 70 kg = 4 tablets, and ≥71 kg = 5 tablets Rifampicin Isoniazid Pyrazinamide Ethambutol
Overall Study STARTED	75	72
Overall Study COMPLETED	65	64
Overall Study NOT COMPLETED	10	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Intervention TB standard therapy with fixed dose combination : once per day by mouth for 2 months Fixed dose combination = RHZE (150mg/75mg/400mg/275mg) R=rifampicin, H=isoniazid, Z=pyrazinamide, E=ethambutol, Patients with body weight: 30 - 37 kg = 2 tablets, 38 - 54 kg = 3 tablets, 55 - 70 kg = 4 tablets, and ≥71 kg = 5 tablets and 166.5 grams cooked fermented soybean (tempeh) daily for two months Rifampicin Isoniazid Pyrazinamide Ethambutol Fermented soybean	Control TB standard therapy with fixed dose combination : once per day by mouth for 2 months Fixed dose combination = RHZE (150mg/75mg/400mg/275mg) R=rifampicin, H=isoniazid, Z=pyrazinamide, E=ethambutol, Patients with body weight: 30 - 37 kg = 2 tablets, 38 - 54 kg = 3 tablets, 55 - 70 kg = 4 tablets, and ≥71 kg = 5 tablets Rifampicin Isoniazid Pyrazinamide Ethambutol
Overall Study Withdrawal by Subject	10	8

Baseline Characteristics

The number of Baseline Participants was assigned to the arm groups based on the inclusion and exclusion criteria. Some of them have rejected and withdrawn for some reasons such as objection and underlying diseases.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Intervention n=65 Participants TB standard therapy with fixed dose combination : once per day by mouth for 2 months Fixed dose combination = RHZE (150mg/75mg/400mg/275mg) R=rifampicin, H=isoniazid, Z=pyrazinamide, E=ethambutol, Patients with body weight: 30 - 37 kg = 2 tablets, 38 - 54 kg = 3 tablets, 55 - 70 kg = 4 tablets, and ≥71 kg = 5 tablets and 166.5 grams cooked fermented soybean (tempeh) daily for two months Rifampicin Isoniazid Pyrazinamide Ethambutol Fermented soybean	Control n=64 Participants TB standard therapy with fixed dose combination : once per day by mouth for 2 months Fixed dose combination = RHZE (150mg/75mg/400mg/275mg) R=rifampicin, H=isoniazid, Z=pyrazinamide, E=ethambutol, Patients with body weight: 30 - 37 kg = 2 tablets, 38 - 54 kg = 3 tablets, 55 - 70 kg = 4 tablets, and ≥71 kg = 5 tablets Rifampicin Isoniazid Pyrazinamide Ethambutol	Total n=129 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants • The number of Baseline Participants was assigned to the arm groups based on the inclusion and exclusion criteria. Some of them have rejected and withdrawn for some reasons such as objection and underlying diseases.	0 Participants n=7 Participants • The number of Baseline Participants was assigned to the arm groups based on the inclusion and exclusion criteria. Some of them have rejected and withdrawn for some reasons such as objection and underlying diseases.	0 Participants n=5 Participants • The number of Baseline Participants was assigned to the arm groups based on the inclusion and exclusion criteria. Some of them have rejected and withdrawn for some reasons such as objection and underlying diseases.
Age, Categorical Between 18 and 65 years	65 Participants n=5 Participants • The number of Baseline Participants was assigned to the arm groups based on the inclusion and exclusion criteria. Some of them have rejected and withdrawn for some reasons such as objection and underlying diseases.	64 Participants n=7 Participants • The number of Baseline Participants was assigned to the arm groups based on the inclusion and exclusion criteria. Some of them have rejected and withdrawn for some reasons such as objection and underlying diseases.	129 Participants n=5 Participants • The number of Baseline Participants was assigned to the arm groups based on the inclusion and exclusion criteria. Some of them have rejected and withdrawn for some reasons such as objection and underlying diseases.
Age, Categorical >=65 years	0 Participants n=5 Participants • The number of Baseline Participants was assigned to the arm groups based on the inclusion and exclusion criteria. Some of them have rejected and withdrawn for some reasons such as objection and underlying diseases.	0 Participants n=7 Participants • The number of Baseline Participants was assigned to the arm groups based on the inclusion and exclusion criteria. Some of them have rejected and withdrawn for some reasons such as objection and underlying diseases.	0 Participants n=5 Participants • The number of Baseline Participants was assigned to the arm groups based on the inclusion and exclusion criteria. Some of them have rejected and withdrawn for some reasons such as objection and underlying diseases.
Age, Continuous	31.11 years STANDARD_DEVIATION 9.63 • n=5 Participants	34.45 years STANDARD_DEVIATION 10.35 • n=7 Participants	32.77 years STANDARD_DEVIATION 10.09 • n=5 Participants
Sex: Female, Male Female	30 Participants n=5 Participants	29 Participants n=7 Participants	59 Participants n=5 Participants
Sex: Female, Male Male	35 Participants n=5 Participants	35 Participants n=7 Participants	70 Participants n=5 Participants
Race/Ethnicity, Customized Javanese	32 Participants n=5 Participants	28 Participants n=7 Participants	60 Participants n=5 Participants
Race/Ethnicity, Customized Madurese	31 Participants n=5 Participants	34 Participants n=7 Participants	65 Participants n=5 Participants
Race/Ethnicity, Customized Others	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment Indonesia · Surabaya, East Java	65 Participants n=5 Participants	64 Participants n=7 Participants	129 Participants n=5 Participants
Region of Enrollment Indonesia · Others	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Body Mass Index	18.41 Kg/m² STANDARD_DEVIATION 3.10 • n=5 Participants	18.57 Kg/m² STANDARD_DEVIATION 3.26 • n=7 Participants	18.49 Kg/m² STANDARD_DEVIATION 3.17 • n=5 Participants
Education Elementary School	26 Participants n=5 Participants	27 Participants n=7 Participants	53 Participants n=5 Participants
Education Middle School	12 Participants n=5 Participants	8 Participants n=7 Participants	20 Participants n=5 Participants
Education High school	23 Participants n=5 Participants	24 Participants n=7 Participants	47 Participants n=5 Participants
Education Bachelor	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Income (million rupiahs) Less than one	38 Participants n=5 Participants	37 Participants n=7 Participants	75 Participants n=5 Participants
Income (million rupiahs) Between one to three	26 Participants n=5 Participants	27 Participants n=7 Participants	53 Participants n=5 Participants
Income (million rupiahs) More than three	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Occupation Unemployed	19 Participants n=5 Participants	22 Participants n=7 Participants	41 Participants n=5 Participants
Occupation Part timer	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Occupation Private	41 Participants n=5 Participants	39 Participants n=7 Participants	80 Participants n=5 Participants
Sputum Smear Positive	44 Participants n=5 Participants	44 Participants n=7 Participants	88 Participants n=5 Participants
Sputum Smear Negative	21 Participants n=5 Participants	20 Participants n=7 Participants	41 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 2 months

Population: All participants were assessed their body weight (kg) using an electronic weight scale before and after the study to determine its change.

Outcome measures

Outcome measures
Measure	Intervention n=65 Participants TB standard therapy with fixed dose combination : once per day by mouth for 2 months Fixed dose combination = RHZE (150mg/75mg/400mg/275mg) R=rifampicin, H=isoniazid, Z=pyrazinamide, E=ethambutol, Patients with body weight: 30 - 37 kg = 2 tablets, 38 - 54 kg = 3 tablets, 55 - 70 kg = 4 tablets, and ≥71 kg = 5 tablets and 166.5 grams cooked fermented soybean (tempeh) daily for two months Rifampicin Isoniazid Pyrazinamide Ethambutol Fermented soybean	Control n=64 Participants TB standard therapy with fixed dose combination : once per day by mouth for 2 months Fixed dose combination = RHZE (150mg/75mg/400mg/275mg) R=rifampicin, H=isoniazid, Z=pyrazinamide, E=ethambutol, Patients with body weight: 30 - 37 kg = 2 tablets, 38 - 54 kg = 3 tablets, 55 - 70 kg = 4 tablets, and ≥71 kg = 5 tablets Rifampicin Isoniazid Pyrazinamide Ethambutol
Change in Bodyweight on a Digital Weight Scale From Baseline at 2 Months	2.80 Kilogram Standard Deviation 2.33	1.44 Kilogram Standard Deviation 2.42

SECONDARY outcome

Timeframe: Baseline, 2 months

Population: All participants were measured from two-times points, before and after the study in order to analyze their change after 2 months of intervention. Higher values reflected better physical function results.

The change of hand-grip strength of the participants over the two months intervention period was measured on a kilograms scale. The change was calculated from two-time points as the value at the later time point minus the value at the earlier time point. Positive numbers represent increases and negative numbers represent decreases. The higher scores reflected the better physical function outcomes of the patients.

Outcome measures

Outcome measures
Measure	Intervention n=65 Participants TB standard therapy with fixed dose combination : once per day by mouth for 2 months Fixed dose combination = RHZE (150mg/75mg/400mg/275mg) R=rifampicin, H=isoniazid, Z=pyrazinamide, E=ethambutol, Patients with body weight: 30 - 37 kg = 2 tablets, 38 - 54 kg = 3 tablets, 55 - 70 kg = 4 tablets, and ≥71 kg = 5 tablets and 166.5 grams cooked fermented soybean (tempeh) daily for two months Rifampicin Isoniazid Pyrazinamide Ethambutol Fermented soybean	Control n=64 Participants TB standard therapy with fixed dose combination : once per day by mouth for 2 months Fixed dose combination = RHZE (150mg/75mg/400mg/275mg) R=rifampicin, H=isoniazid, Z=pyrazinamide, E=ethambutol, Patients with body weight: 30 - 37 kg = 2 tablets, 38 - 54 kg = 3 tablets, 55 - 70 kg = 4 tablets, and ≥71 kg = 5 tablets Rifampicin Isoniazid Pyrazinamide Ethambutol
Change in Hand-grip Strength on a Digital Dynamometer Scale From Baseline at 2 Months	3.90 Kilogram Standard Deviation 4.50	0.84 Kilogram Standard Deviation 4.83

SECONDARY outcome

Timeframe: Baseline, 2 months

Population: Not all participants were analyzed before and after the study to measure the change in the distance. Only 64 participants from the intervention group and 63 participants from the control group contributed to data collection.

The change distance in meters scale as assessed by 6MWT according to American Thoracic Society (ATS) 2002 guidelines. The 6MWT was carried out on a track along the 30-meter corridor marked by two colored cones placed at both ends of the track alignment. The participants were asked using the standard instruction to walk at their self-selected pace back and forth between the cones as far as they could for 6 minutes. The distance taken by each participant was measured and then recorded. Instructions were given to every patient by reading a guideline with the same intonations to every patient before performing the test. The result of the 6MWT was expressed in meters. The change was calculated from two-time points as the value at the later time point minus the value at the earlier time point. Higher scores reflected better physical function outcomes.

Outcome measures

Outcome measures
Measure	Intervention n=64 Participants TB standard therapy with fixed dose combination : once per day by mouth for 2 months Fixed dose combination = RHZE (150mg/75mg/400mg/275mg) R=rifampicin, H=isoniazid, Z=pyrazinamide, E=ethambutol, Patients with body weight: 30 - 37 kg = 2 tablets, 38 - 54 kg = 3 tablets, 55 - 70 kg = 4 tablets, and ≥71 kg = 5 tablets and 166.5 grams cooked fermented soybean (tempeh) daily for two months Rifampicin Isoniazid Pyrazinamide Ethambutol Fermented soybean	Control n=63 Participants TB standard therapy with fixed dose combination : once per day by mouth for 2 months Fixed dose combination = RHZE (150mg/75mg/400mg/275mg) R=rifampicin, H=isoniazid, Z=pyrazinamide, E=ethambutol, Patients with body weight: 30 - 37 kg = 2 tablets, 38 - 54 kg = 3 tablets, 55 - 70 kg = 4 tablets, and ≥71 kg = 5 tablets Rifampicin Isoniazid Pyrazinamide Ethambutol
Change in Distance on 6-minute Walk Test (6MWT) From Baseline at 2 Months	49.67 Meter Standard Deviation 58.49	25.75 Meter Standard Deviation 56.85

SECONDARY outcome

Timeframe: Baseline, 2 months

Population: All participants were assessed before and after the study using a standard formula to determine the change of the body mass index (BMI).

The change in BMI was assessed by a digital weight scale and height scale (kg/m²). The formula for BMI is weight in kilograms divided by height in meters squared. The change was calculated from two-time points as the value at the later time point minus the value at the earlier time point. Higher scores reflected the better nutritional status results of the patients.

Outcome measures

Outcome measures
Measure	Intervention n=65 Participants TB standard therapy with fixed dose combination : once per day by mouth for 2 months Fixed dose combination = RHZE (150mg/75mg/400mg/275mg) R=rifampicin, H=isoniazid, Z=pyrazinamide, E=ethambutol, Patients with body weight: 30 - 37 kg = 2 tablets, 38 - 54 kg = 3 tablets, 55 - 70 kg = 4 tablets, and ≥71 kg = 5 tablets and 166.5 grams cooked fermented soybean (tempeh) daily for two months Rifampicin Isoniazid Pyrazinamide Ethambutol Fermented soybean	Control n=64 Participants TB standard therapy with fixed dose combination : once per day by mouth for 2 months Fixed dose combination = RHZE (150mg/75mg/400mg/275mg) R=rifampicin, H=isoniazid, Z=pyrazinamide, E=ethambutol, Patients with body weight: 30 - 37 kg = 2 tablets, 38 - 54 kg = 3 tablets, 55 - 70 kg = 4 tablets, and ≥71 kg = 5 tablets Rifampicin Isoniazid Pyrazinamide Ethambutol
Change in Body Mass Index (BMI) From Baseline at 2 Months	1.13 Kg/m² Standard Deviation 0.93	0.54 Kg/m² Standard Deviation 0.94

OTHER_PRE_SPECIFIED outcome

Timeframe: In the course of the 8 week intervention, two interviews were conducted; at the 2nd and 6th week.

Population: Not all participants were assessed their calorie intake, only 61 participants in the control arm and all participants from intervention contributed to the data collection.

The average calorie intake (in kcal/day) was assessed by the 24-hour dietary recall questionnaire and calculated by NutriSurvey software version 2005, with the country-specific food database for Indonesia.

Outcome measures

Outcome measures
Measure	Intervention n=65 Participants TB standard therapy with fixed dose combination : once per day by mouth for 2 months Fixed dose combination = RHZE (150mg/75mg/400mg/275mg) R=rifampicin, H=isoniazid, Z=pyrazinamide, E=ethambutol, Patients with body weight: 30 - 37 kg = 2 tablets, 38 - 54 kg = 3 tablets, 55 - 70 kg = 4 tablets, and ≥71 kg = 5 tablets and 166.5 grams cooked fermented soybean (tempeh) daily for two months Rifampicin Isoniazid Pyrazinamide Ethambutol Fermented soybean	Control n=61 Participants TB standard therapy with fixed dose combination : once per day by mouth for 2 months Fixed dose combination = RHZE (150mg/75mg/400mg/275mg) R=rifampicin, H=isoniazid, Z=pyrazinamide, E=ethambutol, Patients with body weight: 30 - 37 kg = 2 tablets, 38 - 54 kg = 3 tablets, 55 - 70 kg = 4 tablets, and ≥71 kg = 5 tablets Rifampicin Isoniazid Pyrazinamide Ethambutol
Caloric Intake on 24-hour Dietary Recall Method at the 2nd and 6th. 2nd week	1980.10 Kcal/day Standard Deviation 437.79	1844.64 Kcal/day Standard Deviation 592.13
Caloric Intake on 24-hour Dietary Recall Method at the 2nd and 6th. 6th week	2227.98 Kcal/day Standard Deviation 463.72	2059.27 Kcal/day Standard Deviation 550.52
Caloric Intake on 24-hour Dietary Recall Method at the 2nd and 6th. Average	2113.16 Kcal/day Standard Deviation 429.41	1972.12 Kcal/day Standard Deviation 530.04

OTHER_PRE_SPECIFIED outcome

Timeframe: In the course of the 8 week intervention, two interviews were conducted; at the 2nd and 6th week.

Population: Not all participants were assessed before and after the study, only 61 participants from the control group contributed to the data collection of the study.

The average protein intake (in Gram/day) was assessed by the 24-hour dietary recall questionnaire and calculated using NutriSurvey software version 2005, with the country specific food database for Indonesia.

Outcome measures

Outcome measures
Measure	Intervention n=65 Participants TB standard therapy with fixed dose combination : once per day by mouth for 2 months Fixed dose combination = RHZE (150mg/75mg/400mg/275mg) R=rifampicin, H=isoniazid, Z=pyrazinamide, E=ethambutol, Patients with body weight: 30 - 37 kg = 2 tablets, 38 - 54 kg = 3 tablets, 55 - 70 kg = 4 tablets, and ≥71 kg = 5 tablets and 166.5 grams cooked fermented soybean (tempeh) daily for two months Rifampicin Isoniazid Pyrazinamide Ethambutol Fermented soybean	Control n=61 Participants TB standard therapy with fixed dose combination : once per day by mouth for 2 months Fixed dose combination = RHZE (150mg/75mg/400mg/275mg) R=rifampicin, H=isoniazid, Z=pyrazinamide, E=ethambutol, Patients with body weight: 30 - 37 kg = 2 tablets, 38 - 54 kg = 3 tablets, 55 - 70 kg = 4 tablets, and ≥71 kg = 5 tablets Rifampicin Isoniazid Pyrazinamide Ethambutol
Protein Intake on 24-hour Dietary Recall Method. 2nd week	77.34 Gram/day Standard Deviation 27.98	69.49 Gram/day Standard Deviation 22.81
Protein Intake on 24-hour Dietary Recall Method. 6th week	77.70 Gram/day Standard Deviation 26.72	73.35 Gram/day Standard Deviation 24.37
Protein Intake on 24-hour Dietary Recall Method. Average	77.52 Gram/day Standard Deviation 26.63	71.42 Gram/day Standard Deviation 21.06

Adverse Events

Intervention

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Control

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Intervention n=75 participants at risk TB standard therapy with fixed dose combination : once per day by mouth for 2 months Fixed dose combination = RHZE (150mg/75mg/400mg/275mg) R=rifampicin, H=isoniazid, Z=pyrazinamide, E=ethambutol, Patients with body weight: 30 - 37 kg = 2 tablets, 38 - 54 kg = 3 tablets, 55 - 70 kg = 4 tablets, and ≥71 kg = 5 tablets and 166.5 grams cooked fermented soybean (tempeh) daily for two months Rifampicin Isoniazid Pyrazinamide Ethambutol Fermented soybean	Control n=72 participants at risk TB standard therapy with fixed dose combination : once per day by mouth for 2 months Fixed dose combination = RHZE (150mg/75mg/400mg/275mg) R=rifampicin, H=isoniazid, Z=pyrazinamide, E=ethambutol, Patients with body weight: 30 - 37 kg = 2 tablets, 38 - 54 kg = 3 tablets, 55 - 70 kg = 4 tablets, and ≥71 kg = 5 tablets Rifampicin Isoniazid Pyrazinamide Ethambutol
Gastrointestinal disorders Vomiting	1.3% 1/75 • Number of events 1 • The intervention period was 2 months for each participant who is eligible for the study. All participants were assessed at month zero (baseline) and month two (end line). The recruitment method was not a one-time event but a referral from physicians. Since eligible participants were not always available every day at the clinics thus the adverse data collection period for all participants was 1 year and 3 months. The definition of adverse event and/or serious adverse event, used to collect adverse event information, are the same from the clinicaltrials.gov definitions. Observation for adverse event was done three times a week since the food should be delivered regularly and regular notes taken on a log book.	0.00% 0/72 • The intervention period was 2 months for each participant who is eligible for the study. All participants were assessed at month zero (baseline) and month two (end line). The recruitment method was not a one-time event but a referral from physicians. Since eligible participants were not always available every day at the clinics thus the adverse data collection period for all participants was 1 year and 3 months. The definition of adverse event and/or serious adverse event, used to collect adverse event information, are the same from the clinicaltrials.gov definitions. Observation for adverse event was done three times a week since the food should be delivered regularly and regular notes taken on a log book.

Additional Information

Dr. Budhi Setiawan

Medical Faculty Wijaya Kusuma Surabaya

Phone: +6287751644522

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place