Introduction and enrollment summary

This document provides an automated summary of data entered from ELICIT. It is generated from a dataset built from the MuSIC server and is updated several times each week. These data lag the actual collected data by roughly one week (for the primary forms) and in some cases longer (e.g. for labs that have a longer turnaround time). Also, because data quality is being monitored, with corrections made and missing data added, there can be some variance in the data from day to day even if new subjects have not been added.

As of today, inital assessment data from 1205 children have been entered (this includes 17 children who were ultimately not eligible)

The number of children with initial assessment data entered by week since enrollment began is as follows:

Eligibility

Of the 17 children who were not eligible, 3 did not consent to participation, 7 expected to move from the study area, 1 had a mother with age < 18, 2 were from a multiple pregnancy, 2 children were not healthy at the time of assessment, 0 had a child weight less than 1.5kg, 2 children were older than 14 days of age, 0 were not eligible for other reasons, and 0 already had a child enrolled in ELICIT. Additionally, 67 children did not remain in the study. 10 of these were due to death.

This leaves 1121 children in the study at present.

Baseline characteristics by randomization arm

Group 1 (n = 285) Group 2 (n = 284) Group 3 (n = 280) Group 4 (n = 272)
child age (days) 6 +/- 3.5 5.8 +/- 3.7 6 +/- 3.7 6 +/- 3.7
# male sex (%) 150 (52.6%) 146 (51.4%) 144 (51.4%) 137 (50.4%)
# born in hospital (%) 159 (55.8%) 153 (53.9%) 135 (48.2%) 137 (50.4%)
Median family income med:30000 (min: 5000, max: 6e+05) med:30000 (min: 5000, max: 3e+05) med:30000 (min: 5000, max: 360000) med:30000 (min: 1500, max: 3e+05)
Mother with >= 7 years of education (%) 232/285 (81.4%) 200/284 (70.4%) 208/280 (74.3%) 201/272 (73.9%)
Birth order med:3 (min: 1 max: 12) med:4 (min: 1 max: 12) med:4 (min: 1 max: 12) med:3 (min: 1 max: 12)
# Iraqw 223/285 (78.2%) 234/284 (82.4%) 223/280 (79.6%) 219/272 (80.5%)
# w/ improved sanitation (%) 38/285 (13.3%) 24/284 (8.5%) 26/280 (9.3%) 33/272 (12.1%)
# w/ improved drinking water (%) 190/285 (66.7%) 187/284 (65.8%) 190/280 (67.9%) 178/272 (65.4%)
# treating water (%) 39/285 (13.7%) 28/284 (9.9%) 34/280 (12.1%) 28/272 (10.3%)
# w/ water > 10 minute walk away (%) 234/285 (82.1%) 226/284 (79.6%) 228/280 (81.4%) 216/272 (79.4%)
# w/ electricity (%) 101/285 (35.4%) 102/284 (35.9%) 92/280 (32.9%) 88/272 (32.4%)
# w/ mattress (%) 177/285 (62.1%) 157/284 (55.3%) 151/280 (53.9%) 153/272 (56.2%)
# w/ table (%) 140/285 (49.1%) 111/284 (39.1%) 108/280 (38.6%) 107/272 (39.3%)
# w/ bench (%) 249/285 (87.4%) 239/284 (84.2%) 226/280 (80.7%) 228/272 (83.8%)
# w/ separate kitchen (%) 186/285 (65.3%) 169/284 (59.5%) 176/280 (62.9%) 162/272 (59.6%)
# w/ refrigerator (%) 5/285 (1.8%) 2/284 (0.7%) 2/280 (0.7%) 5/272 (1.8%)
# w/ television (%) 19/285 (6.7%) 18/284 (6.3%) 21/280 (7.5%) 15/272 (5.5%)
# w/ mobile phone (%) 235/285 (82.5%) 242/284 (85.2%) 227/280 (81.1%) 226/272 (83.1%)
# w/ family bank account (%) 22/285 (7.7%) 20/284 (7%) 10/280 (3.6%) 13/272 (4.8%)
# own agricultural land (%) 272/285 (95.4%) 272/284 (95.8%) 271/280 (96.8%) 262/272 (96.3%)
maternal age (years) 28 +/- 7.1 27.7 +/- 6.7 27.8 +/- 6.1 27.7 +/- 6.6
enrollment length (cm) 49.2 +/- 2 min:42.2 max: 59 48.8 +/- 2.1 min:40 max: 57 49.1 +/- 2.1 min:41 max: 55 49.1 +/- 2.1 min:38 max: 57
enrollment weight (kg) 3.1 +/- 0.5 min:1.8 max: 4.6 3.1 +/- 0.5 min:1.9 max: 6.6 3.1 +/- 0.5 min:1.6 max: 4.4 3.2 +/- 0.5 min:1.6 max: 5.7
enrollment head circumference (cm) 34.7 +/- 1.3 min:31 max: 38.2 34.6 +/- 1.3 min:30 max: 38.4 34.8 +/- 1.4 min:28.3 max: 38.5 34.8 +/- 1.3 min:31.5 max: 40

Illness, healthcare accessed, and antibiotic use

Healthcare accessed in last week by child age and nicotinamide assignment

Healthcare accessed in last week by child age and antibiotic assignment

Illness in the last week by child age and nicotinamide treatment assignment:

Illness in the last week by child age and antibiotic treatment assignment:

Antibiotic use in the last week by child age and nicotinamide treatment assignment:

Antibiotic use in the last week by child age and antibiotic treatment assignment:

Adverse events in mothers

To date, there have been 475 adverse events in mothers (251 in NIC-A and 224 in NIC-B). There have been 26 serious adverse events(14 in NIC-A and 12 in NIC-B) and 0 adverse events deemed related or possibily related to study medications (0 in NIC-A and 0 in NIC-B).

Serious adverse event categories in mothers by nicotinamide arm:

NIC-A NIC-B
Any Serious AE 14 (5.6%) 12 (5.4%)
ALRI 0 3
diarrhea 4 2
DVT 1 0
Lab abnormality 1 0
Other 4 4
Partial intestinal obstruction 2 0
Sepsis 2 2
Septicemia 0 1

The “other” serious AEs for NIC-A were as follows: EPILEPSY, ACUTE ASTHMATIC ATTACK, 1. UNSPECIFIED RESPIRATORY ILLNESS, UNSPECIFIED ILLNESS

The “other” serious AEs for NIC-B were as follows: POSTPARTUM PRE ECLAMPSIA, SCHIZOAFFECTIVE DISORDER, SUSPECTED ORGANOPHOSPHATE POISONING, SEIZURE DISORDER

Adverse events in children

By Nicotinamide arm:

To date, there have been 3312 adverse events in children (1650 in NIC-A and 1662 in NIC-B). There have been 198 serious adverse events(99 in NIC-A and 99 in NIC-B) and 0 adverse events deemed related or possibily related to study medications (0 in NIC-A and 0 in NIC-B).

All adeverse events by nicotinimide arm for children six months and older

NIC-A NIC-B
Acute watery diarrhea 19 29
ALRI 218 234
Constipation 4 0
diarrhea 370 382
Dysentery 5 8
Ear infection 14 8
fever 28 32
Fungal infection 2 3
Injury/Burn 4 16
Lab abnormality 66 49
Malnutrition 4 3
Ophthamalogical illness 16 14
Other 12 20
Septicemia 0 2
Skin rash/infection 37 44
URTI 49 44
UTI 1 0
Vomitting 1 3

The “other” AEs for NIC-A were as follows: UNSPECIFIED ILLNESS, UNSPECIFIED ILLNESS, UNSPECIFIED ILLNESS., UNSPECIFIED ORAL INFECTION., UNSPECIFIED ENT ILLNESS, ARTI, UNSPECIFIED ILLNESS, ORAL TRUSH, UNSPECIFIED ILLNESS, UNSPECIFIED ILLNESS, LOSS OF APPETITE, UNSPECIFIED ILLNESS

The “other” AEs for NIC-B were as follows: ADVERSE DRUG REACTION DUE TO OVERDOSE., SCABIES, GATROENTERITIS , UNSPECIFIED ILLNESS., UNSPECIFIED ILLNESS, UNSPECIFIED ILLNESS, TONSILLITIS, UNSPECIFIED ILLNESS, UNSPECIFIED ILLNESS., UNSPECIFIED ILLNESS., USPECIFIED ILLNESS., LRI, UNSPECIFIED ILLNESS., UNSPECIFIED ILLNESS., UNSPECIFIED ILLNESS, UNSPECIFIED ILLNESS, UNSPECIFIED ILLNESS, UNSPECIFIED INFECTION ON THE THUMB., CHICKEN POX, UNSPECIFIED ILLNESS

Serious adverse events by nicotinamide arm for children older than six months

NIC-A NIC-B
Any Serious AE 48 (5.6%) 45 (5.1%)
Acute watery diarrhea 0 1
ALRI 5 9
diarrhea 35 27
Dysentery 0 1
Injury/Burn 1 1
Lab abnormality 0 1
Malnutrition 4 1
Ophthamalogical illness 1 0
Other 0 1
Septicemia 0 1
URTI 2 2

The “other” serious AEs for NIC-A were as follows:

The “other” serious AEs for NIC-B were as follows: CHICKEN POX

Serious adverse events by nicotinamide arm for children less than 6 months old

NIC-A NIC-B
Any Serious AE 51 (6.4%) 54 (7%)
ALRI 26 19
diarrhea 11 18
Jaundice 0 1
Lab abnormality 3 0
Malnutrition 2 0
Sepsis 6 10
Skin rash/infection 0 1
URTI 3 4
UTI 0 1

The “other” serious AEs for NIC-A were as follows:

The “other” serious AEs for NIC-B were as follows:

By antibiotic arm

To date, there have been 1741 adverse events in children 6 months and older, (897 in ANTI-A and 844 in ANTI-B). There have been 93 serious adverse events(44 in ANTI-A and 49 in ANTI-B) and 0 adverse events deemed related or possibily related to study medications (0 in ANTI-A and 0 in ANTI-B).

All adverse events for children older than 6 months

ANTI-A ANTI-B
Acute watery diarrhea 27 21
ALRI 249 203
Constipation 1 3
diarrhea 371 381
Dysentery 8 5
Ear infection 13 9
fever 29 31
Fungal infection 2 3
Injury/Burn 11 9
Lab abnormality 54 61
Malnutrition 5 2
Ophthamalogical illness 18 12
Other 13 19
Septicemia 1 1
Skin rash/infection 45 36
URTI 49 44
UTI 0 1
Vomitting 1 3

The “other” AEs for ANTI-A were as follows: UNSPECIFIED ILLNESS., SCABIES, GATROENTERITIS , UNSPECIFIED ORAL INFECTION., UNSPECIFIED ENT ILLNESS, TONSILLITIS, UNSPECIFIED ILLNESS, LRI, UNSPECIFIED ILLNESS., UNSPECIFIED ILLNESS, UNSPECIFIED ILLNESS, LOSS OF APPETITE, UNSPECIFIED ILLNESS

The “other” AEs fo ANTI-B were as follows: UNSPECIFIED ILLNESS, UNSPECIFIED ILLNESS, ADVERSE DRUG REACTION DUE TO OVERDOSE., UNSPECIFIED ILLNESS., UNSPECIFIED ILLNESS, UNSPECIFIED ILLNESS, UNSPECIFIED ILLNESS, UNSPECIFIED ILLNESS., UNSPECIFIED ILLNESS., ARTI, USPECIFIED ILLNESS., ORAL TRUSH, UNSPECIFIED ILLNESS., UNSPECIFIED ILLNESS, UNSPECIFIED ILLNESS, UNSPECIFIED INFECTION ON THE THUMB., CHICKEN POX, UNSPECIFIED ILLNESS, UNSPECIFIED ILLNESS

Serious adverse events for children older than 6 months

ANTI-A ANTI-B
Any Serious AE 44 (4.9%) 49 (5.8%)
Acute watery diarrhea 0 1
ALRI 7 7
diarrhea 28 34
Dysentery 1 0
Injury/Burn 1 1
Lab abnormality 0 1
Malnutrition 4 1
Ophthamalogical illness 1 0
Other 0 1
Septicemia 0 1
URTI 2 2

The “other” serious AEs for ANTI-A were as follows:

The “other” serious AEs fo ANTI-B were as follows: CHICKEN POX

All serious adverse events for children older than 6 months by randomization arm

1 2 3 4
Any Serious AE 25 (5.9%) 23 (5.4%) 19 (4%) 26 (6.2%)
Acute watery diarrhea 0 0 0 1
ALRI 4 1 3 6
diarrhea 15 20 13 14
Dysentery 0 0 1 0
Injury/Burn 1 0 0 1
Lab abnormality 0 0 0 1
Malnutrition 3 1 1 0
Ophthamalogical illness 1 0 0 0
Other 0 0 0 1
Septicemia 0 0 0 1
URTI 1 1 1 1

All serious adverse events for children of all ages by randomization arm

1 2 3 4
Any Serious AE 50 (6.2%) 49 (5.8%) 49 (5.6%) 50 (6.3%)
Acute watery diarrhea 0 0 0 1
ALRI 19 12 17 11
diarrhea 19 27 23 22
Dysentery 0 0 1 0
Injury/Burn 1 0 0 1
Jaundice 0 0 0 1
Lab abnormality 2 1 0 1
Malnutrition 5 1 1 0
Ophthamalogical illness 1 0 0 0
Other 0 0 0 1
Sepsis 2 4 4 6
Septicemia 0 0 0 1
Skin rash/infection 0 0 1 0
URTI 1 4 2 4
UTI 0 0 0 1

All adverse events for children older than 6 months by randomization arm

1 2 3 4
Any AE 424 426 473 418
Acute watery diarrhea 11 8 16 13
ALRI 124 94 125 109
Constipation 1 3 0 0
diarrhea 159 211 212 170
Dysentery 3 2 5 3
Ear infection 8 6 5 3
fever 16 12 13 19
Fungal infection 1 1 1 2
Injury/Burn 4 0 7 9
Lab abnormality 30 36 24 25
Malnutrition 3 1 2 1
Ophthamalogical illness 9 7 9 5
Other 6 6 7 13
Septicemia 0 0 1 1
Skin rash/infection 23 14 22 22
URTI 26 23 23 21
UTI 0 1 0 0
Vomitting 0 1 1 2

All adverse events for children of all ages by randomization arm

1 2 3 4
Any AE 812 838 871 791
Acute watery diarrhea 11 8 17 14
ALRI 316 293 322 265
Constipation 3 3 1 0
diarrhea 243 317 304 265
Dysentery 3 3 6 7
Ear infection 13 11 8 10
fever 22 25 18 26
Fungal infection 3 2 2 3
Injury/Burn 5 0 9 9
Jaundice 0 0 0 1
Lab abnormality 34 40 28 28
Malnutrition 5 1 2 1
Omphalitis 3 0 1 0
Ophthamalogical illness 19 16 17 14
Other 20 24 26 31
Sepsis 4 5 8 10
Septicemia 1 0 1 1
Skin rash/infection 44 28 42 37
URTI 63 59 55 60
UTI 0 2 2 6
Vomitting 0 1 2 3

Protocol deviations by nicotanmide arm

NIC-A NIC-B
Any protocol deviation 158 142
Inappropriate documentation of consent 0 1
Study medication given outside of time window 35 37
Study antimicrobials given prior to stool colelction 4 1
Incorrect does of study medication 6 6
Delay of AE/SAE reporting 7 14
Blood for safety labs at 2 months (first 100 participants) not obtained 105 82

Protocol deviations by antibiotic arm

ANTI-A ANTI-B
Any protocol deviation 141 159
Inappropriate documentation of consent 0 1
Study medication given outside of time window 39 33
Study antimicrobials given prior to stool colelction 3 2
Incorrect does of study medication 6 6
Delay of AE/SAE reporting 8 13
Blood for safety labs at 2 months (first 100 participants) not obtained 85 102

Protocol deviations by study arm

1 2 3 4
Any protocol deviation 70 88 71 71
Inappropriate documentation of consent 0 0 0 1
Study medication given outside of time window 17 18 22 15
Study antimicrobials given prior to stool colelction 3 1 0 1
Incorrect does of study medication 2 4 4 2
Delay of AE/SAE reporting 1 6 7 7
Blood for safety labs at 2 months (first 100 participants) not obtained 47 58 38 44

Compliance with study medications

Objective nicotanimide pill/packet compliance (based on pill/packet counting performed every 2 months starting at the 2 month visit):