Table 1.
Characteristics of Trials Identified in the Systematic Review
| First Author, a Year (Reference No.) | Registration | Country | Publication Type b | Publication Status | Intervention | Control | Study Design | Unit of Randomization | Stratification | Primary Outcome Disease | Study Setting |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Barnabas, 2021, 2020 (55, 100) | NCT 04328961 | United States | Study protocol; article | Completed | Hydroxy-chloroquine as prophylactic | Ascorbic acid | Ring trial | Household | Study site and type of contact (household member vs. health care worker) | COVID-19 | Emergency/emerging infection |
| Bath, 2021 (17) | NCT 02556242 | South Africa | Article | Completed | Reactive, targeted, indoor residual spraying | Standard indoor residual spraying | Cluster RCT | Census ward | Historical malaria and indoor residual spraying coverage, population size and density, and length of waterways | Malaria | Elimination |
| Bridges, 2017, 2016 (18, 101) | NCT 02654912 | Zambia | Study protocol; trial registration | Recruitment complete | Presumptive antimalarial treatment of population within 140 m of index cases | Testing and treatment of positive individuals within 140 m of index cases | Cluster RCT | Health-facility catchment area | None | Malaria | Elimination |
| Coldiron, 2018, 2017 (48, 102) | NCT 02724046 | Niger | Protocol; article | Completed | Ciprofloxacin treatment of index case household or village | Standard of care | Cluster RCT | Village | None | Meningitis | Outbreak |
| Cowling, 2008 (75) | NCT 00425893 | Hong Kong | Article (preliminary results) | Completed | 1) Health education plus mask intervention 2) Health education plus handwashing intervention |
General health education | Ring trial | Household | None | Influenza | Seasonal epidemic |
| Echevarría, 1995 (51) | N/A | Peru | Article | Completed | Single-dose ciprofloxacin | Placebo | RCT | Not indicated | None | Cholera | Endemic infection |
| Egsmose, 1965 (103) | N/A | Kenya | Article | Completed | 1-year course of isoniazid | Placebo | Ring trial | Household | None | Pulmonary tuberculosis | Endemic infection |
| Eisele, 2015, 2020, 2016 (19, 74, 104) | NCT 02329301 | Zambia | Study protocol; article; article | Completed | Household-level focal mass drug administration | Community-level mass drug administration | Cluster RCT | Health-facility catchment area | Low vs. moderate transmission | Malaria | Elimination setting |
| Fritz, 2012 (105) | NCT 00731783 | United States | Article | Completed | Household infection decolonization | Decolonization of infected individual | Ring trial | Household (intervention) or individual (control) | None | Staphylococcus aureus infection | Epidemic infection |
| George, 2021 (106); Masud, 2020 (107) | NCT 04008134 | Bangladesh | Article; article | Completed | Mobile health program focused on handwashing promotion, or mobile health program plus home visits | Standard message on oral rehydration | Ring trial | Household | Study site, hospital ward, and treatment location | Diarrhea | Endemic infection |
| Halperin, 1999 (52) | N/A | Canada | Article | Completed | Erythromycin estolate for 10 days | Placebo | Ring trial | Household | None | Bordetella pertussis infection | Outbreak |
| Hayden, 2000 (60) | N/A | United States, Canada, United Kingdom, Finland | Article | Completed | Inhaled zanamivir as prophylactic | Placebo administered through inhaler | Ring trial | Family | None | Influenza | Seasonal epidemic |
| Hayden, 2004 (68) | N/A | United States, Estonia, United Kingdom | Article | Completed | Oseltamivir as prophylactic | No household treatment except for the index case | Ring trial | Household | Presence of an infant or a second case in the household | Influenza | Seasonal epidemic |
| Henao-Restrepo, 2017, 2015, 2015 (24, 42, 109) | PACTR 2015–03001 057193 | Guinea | Article; article; study protocol | Completed | Ebola Virus vaccination of contacts and contacts of contacts of index cases | Delayed Ebola virus vaccination of contacts and contacts of contacts of index cases after 21 days | Ring trial | Contacts and contacts of contacts of index cases | Location (urban vs. rural), ring size (<21 vs. >20) | Ebola virus disease | Emergency/emerging infection |
| Herzog, 1986 (54) | N/A | Switzerland | Article | Completed | Low-dose intranasal recombinant leucocyte IFN-αA, Ro 22–8181 as prophylactic | Placebo | Ring trial | Family | None | Common cold | Seasonal epidemic |
| Hsiang, 2020, 2015 (21, 111); Medzihradsky, 2018 (110) | NCT 02610400 | Namibia | Article; study protocol; trial registration | Completed | 1) Presumptive antimalarial treatment of population within 500 m of index cases; 2) indoor residual spraying within 500 m of index cases | 1) Testing and treatment of positive individuals within 500 m of index cases; 2) Indoor residual spraying within 500 m of index cases | Cluster RCT with factorial design | Census enumeration area | Historical malaria incidence, population size and density, and distance from household to health care facility | Malaria | Elimination |
| Ikematsu, 2020 (56) | JapicCTI- 184180 | Japan | Article | Completed | Baloxavir as prophylactic | Placebo | Ring-stratified RCT | Individuals | Time from illness onset to enrollment; treatment of index patient; participant age | Influenza | Seasonal epidemic |
| Iturriaga, 2021 (112) | NCT 04552379 | Chile | Study protocol | Recruitment ongoing | Pegylated IFN β-1a subcutaneous treatment as prophylactic | Standard of care | Ring trial | Household | Number of people in household | COVID-19 | Emergency/emerging infection |
| Kashiwagi, 2013 (57) | JapicCTI-111647 | Japan | Article | Completed | Inhaled laninamivir octanoate as prophylactic | Placebo | Ring-stratified RCT | Individuals | Institution; index patient infection with influenza A or B | Influenza | Seasonal epidemic |
| Kashiwagi, 2016 (58) | JapicCTI-142679 | Japan | Article | Completed | Inhaled laninamivir octanoate as prophylactic | Placebo | Ring-stratified RCT | Individuals | Virus type of index case; participants’ influenza vaccination status in 2014–2015 influenza season | Influenza | Seasonal epidemic |
| Low, 2006 (113) | NCT 00112255 | England | Article | Completed | Partner notification immediately initiated by practice nurse | Referral to specialist clinic | Ring trial | Sexual partners of index case | Medical practice | Chlamydia | Endemic infection |
| Mitjà, 2021 (67) | NCT 04304053 | Spain | Article | Completed | Hydroxy-chloroquine as prophylactic | Usual care | Ring trial | Ring (e.g., household contacts, health care workers, nursing-home residents) | None | COVID-19 | Emergency/emerging infection |
| Murphy, 1983 (114) | N/A | United States | Article | Completed | Rifampin as prophylactic | Placebo | Ring trial | Contact unit (members of index household and nonresident contacts) | None | Influenza | Seasonal epidemic |
| Nakano, 2016 (59) | N/A | Japan | Article | Completed | Inhaled laninamivir octanoate as prophylactic | Placebo | Ring-stratified RCT | Individuals | Virus types for the index case patient; participants’ influenza vaccination status | Influenza | Seasonal epidemic |
| Nanni, 2020 (115) | NCT 04363827 | Italy | Study protocol | Trial ongoing | 1) Hydroxy-chloroquine treatment for 1 month; 2) hydroxy-chloroquine treatment for 5–7 days as prophylactic | Observation | Ring trial | Household members and/or contacts) | Province COVID-19 incidence; index case patient is health care worker; index case COVID-19 treatment | COVID-19 | Emergency/emerging infection |
| Okebe, 2021 (49) | NCT 02878200 | Gambia | Article | Completed | Presumptive dihydro-artemisinin-piperaquine treatment for all compound members of index case | Screening of compound members of index case | Cluster RCT | Village | Previous leprosy incidence | Malaria | Endemic infection |
| Ortuno-Gutierrez, 2019 (37); De Jong, 2018 (116) | NCT 03662022 | Comoros and Madagascar | Protocol; trial registration | Active, recruitment complete | Postexposure prophylaxis provided to household members of index case patient, neighborhood contacts within 100 m, or contacts within 100 m who test positive for a serological marker | No postexposure prophylaxis | Cluster RCT | Village | None | Leprosy | Hyperendemic infection |
| Ram, 2015 (63) | NCT 00880659 | Bangladesh | Article | Completed | Intensive handwashing (soap and daily handwashing) behavioral promotion and provision of handwashing station | Standard practices | Ring trial | Household compounds | None | Influenza-like illness | Seasonal epidemic |
| Sagliocca, 1999 (117) | N/A | Italy | Article | Completed | Hepatitis A vaccine | No vaccine | Ring trial | Household | None | Hepatitis A infection | Endemic infection |
| Salazar-Austin, 2020 (50) | NCT 03074799 | South Africa | Article | Completed | Symptom-based tuberculosis screening of contacts | Skin test–based screening of tuberculosis contacts | Cluster RCT | Clinic | Case notification rate and distance to hospital | Tuberculosis | Endemic infection |
| Seddon, 2018 (118) | ISRCTN 92634082 | South Africa | Study protocol | Ongoing | Daily levofloxacin for 24 weeks | Placebo | Ring trial | Household | Study site | Tuberculosis | Endemic infection |
| Smit, 2020 (76); Calmy, 2020 (119) | NCT 04364022 | Switzerland | Study protocol; trial registration | Recruitment complete | Prophylactic lopinavir/ritonavir treatment of households with an asymptomatic index case patient | No treatment of households with an asymptomatic index case patient (standard of care) | Ring-stratified cluster RCT | Household | Study site | COVID-19 | Emergency/emerging infection |
| Suess, 2012 (65) | NCT 00833885 | Germany | Article | Completed | 1) Mask/hygiene: households provided with face masks and alcohol-based hand cleaner and information on proper use; 2) mask: households provided with surgical face masks and information on correct use | No masks or hand cleaner provided | Ring trial | Household | None | Influenza | Seasonal epidemic |
| Tan, 2021 (77) | NCT 04321174 | Canada | Study protocol | Recruitment ongoing | Oral lopinavir/ritonavir course for 2 weeks as prophylactic | No intervention | Ring trial | Ring (e.g., household members, health care workers) | Study site | COVID-19 | Emergency/emerging infection |
| van der Sande, 2014, 2010 (61, 120) | NCT 01053377; NL92738 | Netherlands | Article; trial registration | Completed | Oseltamivir as prophylactic | Placebo | Cluster RCT | Nursing-home unit | None | Influenza | Seasonal epidemic |
| Vasiliu, 2021 (121) | NCT 03832023 | Cameroon and Uganda | Protocol | Recruiting | Community-based tuberculosis screening of household contacts | Facility-based standard of care | Cluster RCT | Health-facility catchment area | Country | Tuberculosis | Endemic infection |
| Vilakati, 2021 (20); Hsiang, 2014 (122) | NCT 02315690 | Eswatini | Article; trial registration | Completed | Presumptive antimalarial treatment of population within 200 m of index cases | Testing and treatment of positive individuals within 500 m of index cases | Cluster RCT | Locality | Malaria history; cluster size | Malaria | Elimination |
| Wamuti, 2015 (123); Cherutich 2017 (124) | NCT 01616420 | Kenya | Protocol | Completed | Assisted partner notification services immediately after index case enrollment | 6-week delayed assisted partner notification about services | Cluster RCT | HIV testing site | Country and rurality | HIV | Epidemic infection |
| Wang, 2021 (125) | NCT 04536298 | United States | Study protocol | Recruitment ongoing | High-dose vitamin D3 supplementation as 1) early treatment, and 2) prophylactic | Placebo capsule of identical appearance and taste | Ring trial | Dyads (index case patient plus closest household member) | None | COVID-19 | Emergency/emerging infection |
| Welliver, 2001 (53) | N/A | Belgium, Canada, Denmark, Finland, Germany, Netherlands, Norway, Switzerland, United Kingdom, United States | Article | Completed | Oseltamivir as prophylactic | Placebo | Ring trial | Household | None | Influenza | Seasonal epidemic |
| Wingfield, 2017 (126) | N/A | Peru | Article | Completed | Standard of care plus socioeconomic support | Standard of care | Ring trial | Household | None | Tuberculosis | Endemic infection |
| Agrawal, 2020 (127) | NCT 04342156 | Singapore | Trial registration | Withdrawn | Hydroxy-chloroquine sulfate | No treatment | Ring trial | Household | None | COVID-19 | Emergency/emerging infection |
| Bardin, 2020 (128) | NCT 04343248 | United States | Trial registration | Trial ongoing | Nitazoxanide as prophylactic, with vitamin super B-complex as dietary supplement | Placebo, with vitamin super B-complex as dietary supplement | RCTc | Not specified | None | COVID-19 and other viral respiratory illnesses | Emergency/emerging infection |
| Bennett, 2020 (129) | NCT 04416945 | Lao People’s Democratic Republic | Trial registration | Not yet recruiting | Testing and treatment of positive individuals in 5 nearest households to index case patient | Standard of care and village-based RACD | Cluster RCT | Health-facility catchment area | None | Malaria | Elimination setting |
| Borrie, 2020 (130) | NCT 04397328 | Canada | Trial registration | Not yet recruiting | Hydroxy-chloroquine as prophylactic | Placebo | RCTc | Not specified | None | COVID-19 | Emergency/emerging infection |
| Bracchi, 2021 (131) | NCT 04842331 | United Kingdom | Trial registration | Recruitment ongoing | RESP301 (nitric oxide–generating solution) as prophylactic, with standard of care | Standard of care | Ring trial | Household | None | COVID-19 | Emergency/emerging infection |
| Elvira, 2021 (132) | NCT 04938596 | Chile | Trial registration | Not yet recruiting | Combination of mask provision, prevention recommendations, and education about tuberculosis | Standard of care | Cluster RCT | Health care area and corresponding clinics | None | Tuberculosis | Endemic infection |
| Gadisa, 2020 (133) | NCT 04241705 | Ethiopia | Trial registration | Recruitment ongoing | 1) Presumptive antimalarial treatment of population within 100 m of index case patients; 2) testing and treatment of positive individuals within 100 m of index case patients | Standard of care | Cluster RCT | District | None | Malaria | Elimination |
| Giles, 2020 (134) | NCT 04318444 | United States | Trial registration | Recruitment ongoing | Hydroxy-chloroquine as prophylactic | Placebo | RCTc | Not specified | None | COVID-19 | Emergency/emerging infection |
| Malin, 2021 (135) | NCT 04894474 | Not specified | Trial registration | Withdrawn | Antibody BI 767551 medication | Placebo | RCTc | Individual | None | COVID-19 | Emergency/emerging infection |
| McGeer, 2020 (136) | NCT 04448119 | Canada | Trial registration | Active, recruitment complete | Favipiravir | Placebo | Ring trial | Long-term care home | None | COVID-19 | Emergency/emerging infection |
| Sued, 2021 (137) | NCT 04788407 | Argentina | Trial registration | Recruitment ongoing | Nitazoxanide as prophylactic | Placebo | RCTc | Not specified | None | COVID-19 | Emergency/emerging infection |
Abbreviations: HIV, human immunodeficiency virus; N/A, not applicable; RACD, reactive case detection; RCT, randomized controlled trial.
a First author’s last name for published articles, preprints, or protocols. Principal investigator’s last name for trial registrations with no publication.
b Includes all types of articles retrieved in the systematic review.
c Insufficient information to determine type of trial.